EP0659186A1 - Indolizines as herbicides - Google Patents

Abstract

A herbicidal composition comprising a compound of formula (I) or a tautomer or a quaternised derivative thereof where Y is a group of formula -CR1=CR2-CO- and R?1, R2, R3, R4 and R5¿ are independently selected from hydrogen; optionally substituted alkyl; optionally alkenyl; optionally substituted alkynyl; optionally substituted aryl; optionally substituted aromatic heterocyclic; halo; nitro; cyano; a group OR6 where R6 is hydrogen or a salt thereof, carboxy or an ester thereof, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aryl; carboxy or a salt, ester or amide derivative thereof; S(O)¿nR?7 where n is 0, 1 or 2 and R7 is optionally alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl; NR8R9 where R?8 and R9¿ are independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl and R9 may additionally be acyl, or R?8 and R9¿ together with the nitrogen atom to which they are attached form a heterocyclic ring; or R?1 and R2¿ and/or any adjacent two of R?3, R4 and R5¿ together with the carbon atoms to which they are attached form an optionally substituted fused saturated or unsaturated carbocyclic or heterocyclic ring; in combination with a carrier or diluent.

Description

IndoHzines as herbicides

The present invention relates to herbicidal compositions containing bicyclic compounds to novel herbicidal bicyclic compounds and to processes for their preparation.

Certain indolizine-5,8-diones are known in the chemical literature (see Tet. Lett. 33, pp 7811-7814 1992 and J. Chem. Soc Perkin Trans 1 1990, pp 1463-1467) .

The applicants have found that such compounds and related compounds are useful as herbicides.

According to the present invention there is provided a herbicidal composition comprising a compound of formula (I), or a tautomer or a

1 2 quaternised derivative thereof where Y is a group of formula -CR =CR -C0- and R , R , R , R and R are independently selected from hydrogen; optionally substituted alkyl; optionally substituted alkenyl; optionally substituted alkynyl; optionally substituted aryl; optionally substituted aromatic heterocyclic; halo; nitro; cyano; a group OR where R is hydrogen or a salt thereof, carboxy or an ester thereof, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aryl; carboxy or a salt, ester or amide derivative thereof; S(0) R where n is 0, 1 or 2 and R is optionally alkyl, optionally substituted alkenyl, optionally substituted alkynyl or

8 9 8 9 optionally substituted aryl; NR R where R and R are independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally

9 8 9 substituted aryl and R may additionally be acyl, or R and R together with the nitrogen atom to which they are attached form a heterocyclic ring; or R and R and/or any adjacent two of R , R and R together with the carbon atoms to which they are attached form an optionally substituted fused saturated or unsaturated carbocyclic or heterocyclic ring; in combination with a carrier or diluent.

Examples of such compositions are those compositions comprising a

1 2 3 4 5 compound of formula (I), where R , R , R , R and R are independently selected from hydrogen; optionally substituted alkyl; optionally substituted alkenyl; optionally substituted alkynyl; optionally substituted aryl; optionally substituted aromatic heterocyclic; halo; nitro; cyano; a group OR where R is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aryl; carboxy or a salt, ester or amide derivative thereof; S(0) R where n is 0, 1 or 2 and R is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or

8 9 8 9 optionally substituted aryl; NR R where R and R are independently

9 selected from hydrogen, alkyl, alkenyl or alkynyl and R may additionally

1 2 3 4 5 be acyl; or R and R and/or any adjacent two of R , R and R together with the carbon atoms to which they are attached form a fused saturated or unsaturated carbocyclic or heterocyclic ring; in combination with a carrier or diluent.

Compounds of formula (I) can exist in two orientations of Y i.e. of

1 2 formula (IA) or (IB) . In addition, where R and/or R are hydroxy, the compounds of formula (IA) and (IB) may exist in tautomeric forms and these also form part of the invention.

As used herein the term "alkyl" includes straight or branched alkyl chains, suitably containing up to 10 carbon atoms, preferably from 1 to 6 carbon atoms. The term "alkoxy" relates to such an alkyl group linked with an oxygen atom. The terms "alkenyl" and "alkynyl" includes unsaturated straight or branched chain containing up to 10 carbon atoms, preferably from 2 to 6 carbon atoms. The term "aryl" includes phenyl and naphthyl. The term "acyl" includes groups of formula C(0)R where R is optionally substituted alkyl; such as acetyl. The term "carbocyclic" includes rings of up to 10, preferably up to 7 carbon atoms. The term "heterocyclic" includes rings containing up to 10, preferably up to 7 atoms, up to three of which are selected from oxygen, sulphur or nitrogen. The term "halo" or "halogen" includes chlorine, fluorine, bromine and iodine.

Suitable optional substituents for alkyl, alkenyl or alkynyl groups R , R , R , R , R , R , R , R or R or for carbocyclic or heterocyclic rings formed by two of such groups include one or more groups selected from halogen such as chloro; hydroxy; nitro; optionally substituted aryl; or

11 12 11 12

C(0) R or S(0) R where p is 1 or 2, q is 0, 1 or 2 and R and R are

P 1 13 14 15 13 14 15 independently selected from OR or NR R and R , R and R are independently selected from hydrogen or alkyl; or P(0)R R where R and

R¹⁷ are alkyl.

Suitable optional substituents for aryl groups R , R , R , R , R , R ,

7 8 9 R , R or R and for aryl substituents on said groups include halo, haloalkyl and nitro W Whheenn oonnee oorr mmoore of R , R , R , R , R or R is a salt, ester or amide of carboxy, it is suitably an agriculturally acceptable salt or ester or amide. Examples of agriculturally acceptable salts include sodium, potassium or calcium salts, sulphonium or sulphoxonium salts such as those of formula S(0) R 20R21R21 where q is 0 or 1, or ammonium or quaternary

* 4- 91 99 9^ 9 ι Λ 0 ^* . ammonium ions of formula N R R R R where R , R , R and R are independently selected from optionally substituted alkyl, alkenyl, alkynyl or aryl groups.

Suitable agriculturally acceptable esters include optionally substituted alkyl, alkenyl, alkynyl or aryl esters wherein the optional substiittuueennttss aarree tthhoossee aass ddeeffiinneedd aabboovvee ffoorr RR eettcc.

P Paarrttiiccuullaarr aaggrriiccuullttuurraal]ly acceptable amides are those of formula

1c9 20 19 20 CONR R where R and R are independently selected from hydrogen or alkyl.

As used herein, the expression 'quaternised derivatives' used in relation to formula (I) relates to those compounds of formula (I) where one or more of R , R , R , R or R contain an optionally substituted amino

1 2 3 4 5 group or where two of groups R and R or any adjacent two of R , R and R form a nitrogen containing heterocyclic ring, and in which the nitrogen atoms have been quaternised. Suitable quaternising groups include optionally substituted alkyl such as methyl, ethyl or benzyl.

1 2 Examples of R and R include hydrogen, optionally substituted alkyl, halo, OR where R is as hereinbefore defined, S(O) R where n and R are

8 9 8 9 as hereinbefore defined or NR R where R and R are as hereinbefore defined.

A sub-group of compounds of formula (IA) or (IB) are those where R

2 and R together with the carbon atoms to which they are attached form an optionally substituted fused unsaturated carbocyclic or heterocyclic ring.

Examples of such rings include fused cyclohexenyl, cyclopentenyl, benzo, pyridyl or pyrazinyl rings optionally substituted with for example one or more halo atoms or alkoxy groups and optionally quaternised where appropriate.

Particular examples of such compounds are those of formula (II) : where R , R and R are as defined above and Y , Y and Y are selected from CR , N or N R where R is selected from hydrogen or halogen in

*?fi particular chlorine or fluorine and R is alkyl such as methyl. Suitably

Λ 0 -~V fi not more than two of Y , Y and Y are N or N R

1 2 Particular examples of groups R and R are hydrogen, alkyl such as methyl or ethyl, hydroxy, alkoxy such as methoxy, ethoxy or iso-propoxy, substituted alkoxy such as ethoxycarbonylmethoxy, phenoxy, halo such as chloro or bromo, amino, substituted amino such as substituted piperazine or N,N,N'-trimethylethylene diamine or quaternised forms thereof, n-butylthio, phenylthio or phenylsulphoxy.

1 2 Preferably R and/or R are independently selected from hydrogen, methyl, methoxy, isopropoxy, chloro or phenylthio.

3 4 5 Examples of R , R and R include hydrogen and alkyl such as methyl, halogen such as chlorine or bromine, and nitro.

3 4 5 Preferably R , R and R are hydrogen.

Certain compounds of formula (I) are novel and these form a further aspect of the invention.

Further according to the present invention there is provided a compound of formula (IB) as defined above.

Yet further according to the invention there is provided a compound of formula (IA) as defined above or a tautomer or a quaternised derivative thereof subject to the following provisos:

1 2

(a) R and R do not together form a fused benzo ring;

1 2

(b) where R and R together form a fused aromatic heterocyclic ring, no

3 4 5 two of R , R and R form an optionally subtituted fused aromatic carbocylic or heterocylic ring;

3 4 5 1 2

(c) where R , R and R are all hydrogen, R and R together do not form a

2 fused tetrachloro-benzo ring or R is not NH(C6H5) or Rl and R2 are not both n-butyl;

3 4 5 2 1

(d) where R , R and R are all hydrogen and R is methoxy, R is not methoxy, n-butyl,phenyl, n-butylacetyleno or phenylacetyleno;

4 5 3

(e) when R and R form a fused benzo ring, R is not carboethoxy.

Further novel compounds of formula (I) are 3-nitropyrrolo[l,2-b]- isoquinoline-5,10-dione, 2-bromopyrrolo[1,2-b]isoquinoline-5,10-dione, 2,3-dibromopyrrolo[1,2-b]isoquinoline-5,10-dione, 2,3-dichloropyrrolo- [l,2-b]isoquinoline-5,10-dione and 2-chloropyrrolo[l,2-b]-isoquinoline- -5,10-dione.

Examples of compounds of formula (IA) are set out in Table (I) and Examples of compounds (IB) are set out in Table II. TABLE I

Compounds of formula (IA)

Compound R R^" No

1

2

3

4

5

6

7

8 OCH, OCH,

9 CH₃ ^" CH₃ ^"

10 CH, CH,

11 -CH-CH-CH-CH-

12 •CH*-CH-CH=CH- 3 OCH₂(CH₃)₂ OCH(CH₃)₂ 4 OCH, OCH, 5 -<CH₂)₄- 6 -CC1-CH-CH-CC1

17 -<CH₂)₃- 8 -CF*CH-CH*CH-

19 -CH-CH-CH--CF-

20 0CH(CH₃)₂ CH. 1 -CH-C(OCH₃)-C(0CH₃)-C(OCH₃)• 3

24

25 6

27 8

29

30 TABLE I

Compounds of formula (IA)

Compound No

31 -N=CH-CH=N- H H H 32 -CH=CH-CH=N⁺(CH₃)- CH, CH, H 33 OH Cl H H H 34 0CH₃ H H H H 35 0CH₃ H H H

^SC6^H5 36 0CH₃ CH, H H H 37 0C0 CH₃ H H H 38 H H H

^0C6^H5 ^OC6^H5 39 0CH₂C0₂CH₂CH₃ H H H H h 0 OH H H -CH-CH-CH-CH- 41 -CH-CH-CH-CH- H H Cl 42 -CH=CH-CH»CH- H Cl Cl 43 -CH-CH-CH-CH- H Br Br 44 -CH-CH-CH-CH- H H Br 45 -CH-CH-CH=CH- H NO, H 46 OCH₃ H -CH-CH-CH-CH- 47 OCH₃ H -CH-CH-CH-CH- 48 Cl H H H 49 OCH, H H H 50 OCH. OCH. CH, CH, H 51 -CH-CH-CH-N- CH. CH, H

Compound R No

54 N(CH₃)(CH₂) N(CH₃)₂ H 55 N(CH₃)(CH₂)₂N (CH^l^" H

56 N(CH₃)₂ H 57 S(CH₂)₃CH₃ H

58

CH₃-N

TABLE II Compounds of Formula (IB)

Compound R No

60 OCH, H H H H

61 OCH. H H -CH=CH-CH=CH-

Compounds of formula (IA) can be prepared for example by methods analogous to those described by Comforth et al in J. Chem Soc. Perkin Trans I. 1990. p 1463-1467.

Alternatively compounds of formula (IA) can be prepared by deprotecting and oxidising a compound of formula (III) ; where R 25 is a protecting group such as trimethylsilyl and R , R , R , R and R are as defined in relation to formula (I). Suitably deprotection is effected by reaction either with water or fluoride ion. Suitable oxidising agents include ferric chloride or oxygen (air) . The reaction is suitably effected at moderate temperatures of from 5 to 60°C, conveniently at ambient temperature in the presence of an organic solvent such as xylene or toluene. Compounds of formula (III) are suitably prepared by heating a compound

1 2 3 4 5 25 of formula (IV); where R , R , R , R , R and R are as defined hereinbefore; in the presence of an organic solvent such as xylene.

Suitable temperatures are from 100 to 200°C, conveniently at the reflux temperature of the solvent. Preferably the subsequent conversion to a compound of formula (I) is carried out in situ.

Compounds of formula (IV) can be prepared by reacting a compound of

1 2 formula (V) where R and R are as hereinbefore defined; with a compound of formula (VI); in the presence of a base, and subsequently a protecting

25 group R introduced in to the molecule by conventional techniques.

Suitable bases are strong bases such as n-butyl-lithium, lithium diisopropylamide or sodium hydride.

The reaction is suitably effected in an inert organic solvent such as tetrahydrofuran, dioxan or diethyl ether at low temperatures of from -100 to 0°C under an inert atmosphere of, for example, nitrogen or argon.

Compounds of formula (V) and (VI) are known compounds or can be prepared from known compounds by conventional methods.

Compounds of formula (IA) can be prepared by reacting a compound of formula (VII) ; where R , R , R , R and R are as defined in relation to formula (I), with a dehydrating agent.

Examples of suitable dehydrating agents include phosphorus oxychloride (P0C1₃).

The reaction is suitably effected in a solvent such as pyridine, at temperatures of from 0 to 80°C, conveniently at room temperature.

Compounds of formula (VII) can be prepared by reacting a compound of

1 2 formula (VIII); where R and R are as defined in relation to formula (I), with a compound of formula (VI) ; as hereinbefore defined in the presence of a base.

Suitable bases include strong bases such as sodium hydride. The reaction is suitably effected in a solvent such as tetrahydrofuran or toluene at elevated temperatures of from 25 to 110°C, conveniently at the reflux temperature of the solvent.

This route to compounds of formula (IA) is particularly suitable to

1 2 produce compounds of formula (IA) where R and R together form an optionally substituted fused saturated or unsaturated carbocyclic or heterocyclic ring. Examples of such rings include cyclopentenyl, cyclohexenyl, phenyl and substituted phenyl such as dichlorophenyl, fluorophenyl or tri ethoxyphenyl. Alternatively compounds of formula (IA) can be prepared by dehydrating a compound of formula (IX); where R 1, R2, R3, R4 and R5 are as defined in relation to formula (I). Suitably dehydration is effected by reacting with a dehydrating agent such as acetic anhydride at elevated temperatures of from 25 to 140°C, conveniently at 85°C.

Compounds of formula (IX) can be prepared by reacting a compound of formula (VIII) as hereinbefore defined with a compound of formula (VI) as hereinbefore defined with a Grignard reagent such as ethyl magnesium bromide. Suitably the reaction is effected at moderate temperatures of from 0 to 40°C conveniently at ambient temperature in the presence of a solvent such as tetrahydrofuran or diethyl ether.

Again this route is particularly suitable for the production of

1 2 compounds of formula IA where R and R form a fused ring system, especially pyridyl and pyrazinyl rings.

Compounds of formula (IX) are either known compounds or they can be prepared from known compounds by conventional routes.

In another embodiment, compounds of formula (I) can be prepared by

3 4 5 reacting a compound of formula (X) , where R , R and R are as hereinbefore

26 27 defined with a compound of formula (XI) ; where R and R are independently alkyl groups such as ethyl, in the presence of a base.

Suitable bases include strong bases such as sodium hydride.

The reaction is suitably effected at elevated temperatures of from 25 to 80°C in a solvent such as tetrahydrofuran. Conveniently the reaction is effected at the reflux temperature of the solvent.

Compounds of formula (I) can be converted to different such compounds by manipulation of the substituents R , R , R , R and R by conventional chemical techniques. For example, R 1, R2, R3, R4 and/or R5 can be converted from hydrogen to bromine or chlorine by halogenation using halogenating agents such as n-bromosuccimide or n-chlorosuccimide. The reaction is suitably effected in the presence of a solvent such as dimethylformamide at elevated temperatures of from 25 to 80 C, conveniently at ambient temperature. Alternatively R 3, R4 and/or R5 can be converted from hydrogen to nitro by nitration using nitrating agents such as sodium nitrate in concentrated sulphuric acid.

1 2 Groups R and/or R may be converted from hydroxy to alkoxy groups by reaction with an alkyl halide such as methyl iodide in the presence of a base such as sodium hydride. A suitable solvent for this reation may be dimethylformamide. This reaction will produce compounds of formula (IB) as well as (IA) . These mixtures may be separated by conventional techniques.

1 2 Acylation of hydroxy groups R and/or R will produce the corresponding compound where R is acyl, carboxy or an ester thereof. Reaction with oxalyl chloride in a solvent such as chloroform and with a catalytic quantity of dimethylformamide will convert the hydroxy groups R 1 and/or R2 to chlorine groups. Compounds where R 1 and/or R2 are chloro can be converted to sulphides and amides by reaction with a thiol or amine respectively. The reactions are suitably effected in an inert solvent such as tetrahydrofuran at temperatures of from -78 to 100 C, typically at -30 C to ambient temperatures.

Quaternised derivatives of suitable compounds of formula (I) may be prepared by reaction with an alkyl halide such as methyl iodide in a solvent such as tetrahydrofuran, preferably at elevated temperatures such as the reflux temperature of the solvent.

Examples of such manipulation appear hereinafter.

Compositions containing compounds of formula (I) include both dilute compositions, which are ready for immediate use, and concentrated compositions, which require to be diluted before use, usually with water. Preferably the compositions contain from 0.012 to 902 by weight of the active ingredient. Dilute compositions ready for use preferably contain from 0.012 to 2Z of active ingredient, while concentrated compositions may contain from 202 to 902 of active ingredient, although from 202 to 702 is usually preferred.

The solid compositions may be in the form of granules, or dusting powders wherein the active ingredient is mixed with a finely divided solid diluent, e.g. kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller's earth and gypsum. They may also be in the form of dispersible powders or grains, comprising a wetting agent to facilitate the dispersion of the powder or grains in liquid. Solid compositions in the form of a powder may be applied as foliar dusts.

Liquid compositions may comprise a solution or dispersion of an active ingredient in water optionally containing a surface-active agent, or may comprise a solution or dispersion of an active ingredient in a water-immiscible organic solvent which is dispersed as droplets in water.

Surface-active agents may be of the cationic, anionic, or non-ionic type or mixtures thereof. The cationic agents are, for example, quaternary ammonium compounds (e.g. cetyltri ethylammonium bromide). Suitable anionic agents are soaps; salts of aliphatic mono ester of sulphuric acid, for example sodium lauryl sulphate; and salts of sulphonated aromatic compounds, for example sodium dodecylbenzenesulphonate, sodium,calcium, and ammonium lignosulphonate, butyinaphthalene sulphonate, and a mixture of the sodium salts of diisopropyl and triisopropylnaphthalenesulphonic acid. Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol and cetyl alcohol, or with alkylphenols such as octyl- or nonyl- phenol (e.g. Agral 90) or octyl-cresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, for example sorbitan monolaurate; the condensation products of the partial ester with ethylene oxide; the lecithins; and silicone surface active agents (water soluble surface active agents having a skeleton which comprises a siloxane chain e.g. Silwet L77). A suitable mixture in mineral oil is Atplus 411F.

The aqueous solutions or dispersions may be prepared by dissolving the active ingredient in water or an organic solvent optionally containing wetting or dispersing agent(s) and then, when organic solvents are used, adding the mixture so obtained to water optionally containing wetting or dispersing agent(s). Suitable organic solvents include, for example, ethylene di-chloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, meth lnaphthalene, the xylenes and trichloroethylene.

The compositions for use in the form of aqueous solutions or dispersions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, and the concentrate is then diluted with water before use. The concentrates are usually required to withstand storage for prolonged periods and after such storage, to be capable of dilution with water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Concentrates conveniently contain 20-902, preferably 20-702, by weight of the active ingredient(s) . Dilute preparations ready for use may contain varying amounts of the active ingredient(s) depending upon the intended purpose; amounts of 0.012 to 10.02 and preferably 0.12 to 22, by weight of active ingredient(s) are normally used.

A preferred form of concentrated composition comprising the active ingredient which has been finely divided and which has been dispersed in water in the presence of a surface-active agent and a suspending agent. Suitable suspending agents are hydrophilic colloids and include, for example, polyvinylpyrrolidone and sodium carboxymethylcellulose, and the vegetable gums, for example gum acacia and gum tragacanth. Preferred suspending agents are those which impart thixotropic properties to, and increase the viscosity of the concentrate. Examples of preferred suspending agents include hydrated colloidal mineral silicates, such as montmorillonite, beidellite, nontronite, hectorite, saponite, and saucorite. Bentonite is especially preferred. Other suspending agents include cellulose derivatives and polyvinyl alcohol.

The compounds of formula (I) are active as herbicides and therefore, in a further aspect the invention provides a process for severely damaging or killing unwanted plants which process comprises applying to the plants, or to the growth medium of the plants, a herbicidally effective amount of a compound of formula (I) as hereinbefore defined.

The compounds of formula (I) are active against a broad range of weed species including monocotyledonous and dicotyledonous species.

The compounds of formula (I) may be applied directly to the plant (post-emergence application) or to the soil before the emergence of the plant (pre-emergence application) . They are particularly useful when applied post-emergence.

The rate of application of the compounds of the invention will depend on a number of factors including, for example, the compound chosen for use, the identity of the plants whose growth is to be inhibited, the formulations selected for use and whether the compound is to be applied for foliage or root uptake. As a general guide, however, an application rate of from 0.001 to 20 kilograms per hectare is suitable while from 0.025 to 10 kilograms per hectare may be preferred.

The compositions of the invention may comprise, in addition to one or more compounds of the invention, one or more compounds not of the invention but which possess biological activity for example herbicides, fungicides, insecticides (optionally with an insecticide synergist) and plant growth regulators. Accordingly in yet a still further embodiment the invention provides a herbicidal composition comprising a mixture of at least one herbicidal compound of formula (I) as hereinbefore defined with at least one other herbicide.

The other herbicide may be any herbicide not having the formula (I) . It will generally be a herbicide having a complementary action in the particular application.

Examples of useful complementary herbicides include:

A. benzo-2,l,3-thiadiazin-4-one-2,2-dioxides such as bentazone;

B. hormone herbicides, particularly the phenoxy alkanoic acids such as MCPA, MCPA-thioethyl, dichlorprop, 2,4,5-T, MCPB, 2,4-D, 2,4-DB, mecoprop, trichlopyr, clopyralid, and their derivatives (eg. salts, esters and amides);

C. 1,3 dimethylpyrazole derivatives such as pyrazoxyfen, pyrazoiate and benzofenap;

D. Dinitrophenols and their derivatives (eg. acetates) such as dinoterb, dinoseb and its ester, dinoseb acetate;

E. dinitroaniline herbicides such as dinitramine, trifluraiin, ethalflurolin, pendimethalin, oryzalin;

F. arylurea herbicides such as diuron, flumeturon, metoxuron, neburon, isoproturon, chlorotoluron, chloroxuron, linuron, monolinuron, chlorobromuron, daimuron, methabenzthiazuron;

G. phenylcarbamoyloxyphenylcarbamates such as phenmedipham and desmedipham;

H. 2-phenylpyridazin-3-ones such as chloridazon and norflurazon; I. uracil herbicides such as lenacil, bromacil and terbacil; J. triazine herbicides such as atrazine, simazine, aziprotryne, cyanazine, prometryn, dimethametryn, simetryne, and terbutryn; K. phosphorothioate herbicides such as piperophos, bensulide, and butamifos;

L. thiolcarbamate herbicides such as cycloate, vernolate, molinate,

* * thiobencarb, butylate , EPTC , tri-allate, di-allate, esprocarb, tiocarbazil, pyridate, and dimepiperate; M. 1,2,4-triazin-5-one herbicides such as metamitron and me ribuzin; N. benzoic acid herbicides such as 2,3,6-TBA, dicamba and chloramben; 0. anilide herbicides such as pretilachlor, butachlor, alachlor, propachlor, propanil, metazachlor, metolachlor, acetochlor, and dimethachlor; P. dihalobenzonitrile herbicides such as dichlobenil, bromoxynil and ioxynil; Q. haloalkanoic herbicides such as dalapon, TCA and salts thereof; R. diphenylether herbicides such as lactofen, fluroglycofen or salts or ester thereof, nitrofen, bifenox. aciflurofen and salts and esters thereof, oxyfluorfen, fomesafen, chlornitrofen and chlomethoxyfen;

S. phenoxyphenoxypropionate herbicides such as diclofop and esters thereof such as the methyl ester, fluazifop and esters thereof, haloxyfop and esters thereof, quizalofop and esters thereof and fenoxaprop and esters thereof such as the ethyl ester;

T. cyclohexanedione herbicides such as alloxydim and salts thereof, sethoxydim, cycloxyidim, tralkoxydim, and clethodim;

U. sulfonyl urea herbicides such as chlorosulfuron, sulfometuron, metsulfuron and esters thereof; benzsulfuron and esters thereof such as DPX-M6313, chlorimuron and esters such as the ethyl ester thereof pirimisulfuron and esters such as the methyl ester thereof, 2-[3-(4-methoxy-6-methyl-l,3,5- triazin-zyl)-3-methylureidosulphonyl) benzoic acid esters such as the methyl ester thereof (DPX-LS300) and pyrazosulfuron;

V. imidazolidinone herbicides such as i azaquin, iiπazame habenz, imazapyr and isopropylammonium salts thereof, imazethapyr;

W. arylanilide herbicides such as flamprop and esters thereof, benzoylprop-ethyl, diflufenican;

X. amino acid herbicides such as glyphosate and glufosinate and their salts and esters, sulphosate and bialaphos;

Y. organoarsenical herbicides such as monosodium methanearsonate (MSMA) ;

Z. herbicidal amide derivative such as napropamide, propyzamide, carbetamide, tebutam, bromobutide, isoxaben, naproanilide and naptalam;

AA. miscellaneous herbicides including ethofumesate, cinmethylin, difenzoquat and salts thereof such as the methyl sulphate salt, clomazone, oxadiazon, bromofenoxim, barban, tridiphane, flurochloridone, quinclorac, dithiopyr and mefanacet;

BB. Examples of useful contact herbicides include: bipyridylium herbicides such as those in which the active entity is paraquat and those in which the active entity is diquat; * These compounds are preferably employed in combination with a safener such as dichlormid. The following examples illustrate the invention. Preparations Preparation 1

Preparation of 3-isopropoxy-4-methylcyclobut-3-en-l,2-dione. Methyllithium (10.2ml of a 1.5 molar solution of 1:1 methyllithium/lithium bromide complex in ether) was added dropwise to a solution of 3,4-diisopropoxycyclobut-3-en-l,2-dione (3.0g) in dry tetrahydrofuran at -78°C under a nitrogen atmosphere. After % hour, water (5ml) was added dropwise and the mixture was allowed to warm to room temperature. After dilution with ether, the aqueous layer was separated and washed with dichloromethane (x2) . The combined organic phases were dried over sodium sulphate and evaporated to a viscous oil (3.36g). This was dissolved in dichloromethane (80ml) and concentrated hydrochloric acid (10 drops) was added at room temperature. The reaction was stirred for 35 minutes, diluted with dichloromethane (80ml), dried over anhydrous potassium carbonate and evaporated to a brown oil. Flash chromatography on silica, eluting with ether/hexane (3:7) gave

3-isopropoxy-4-methylcyclobut-3-en-l,2-dione as a pale yellow oil, yield 2.26g. ^λE NMR (CDC1₃): δ 5.40(lH,hept) ; 2.21(3H,s); 1.47(6H,d). Preparation 2

Preparation of 3-chloro-4-isopropoxy-cyclobut-3-en-l,2-dione. Isopropanol (2ml) was added to a solution of 3,4-dichloro-3-cyclobuten-l, 2-dione (6.0g) (prepared according to the method of De Sel s, Fox and Riordan, Tetrahedron Letters, No. 10, pp. 781-782, 1970) in dry tetrahydrofuran, and the solution was heated to reflux for 4 hours and then left standing overnight. The solvent was evaporated under reduced pressure and the residue purified by flash chromatography on silica, eluting with ethyl acetate/hexane (3:17) to give the title compound as an orange oil, yield 1.66g. ^XH NMR (CDClg): δ 5.47(lH,hept) ; 1.53(6H,d). Preparation 3

Preparation of 4-methoxy-3-phenylthio-cyclobut-3-en-l,2-dione. Triethylamine (5.05ml) was added to a solution of 3-chloro-4-methoxy- cyclobut-3-en-l,2-dione (2.65g) in dichloromethane (30ml) at 0°C under an atmosphere of nitrogen. Thiophenol (2.23ml) was then added dropwise and stirred for 1 hour. The resulting solid was filtered under suction, washing with a little dichloromethane and the filtrate was evaporated to give a solid. This was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (1:4) to give the title compound as a yellow oil, yield 2.70g. ^"4. NMR (CDC1₃): δ 7.58-7.35(5H,m) ; 4.37(3H,s). Preparation 4

Preparation of 3, -diphenoxycyclobut-3-en-1.2-dione.

Triethylamine (8.32ml) was added to a solution of 3, -dichlorocyclobut-3-

-en-l,2-dione (3.0g) and phenol (5.62g) in dichloromethane at 0°C under a nitrogen atmosphere. After 1 hour at 0°C, the reaction mixture was filtered through a silica pad, washing with dichloromethane. Evaporation of the filtrate gave a dark brown oily solid which was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (1:4), followed by crystallisation from ethyl acetate to give the title compound as a white powder, yield 1.34g. ¹H NMR (CDCl_j): δ 7.46(2H,d); 7.42(2H,d); 7.32(2H,d);

7.30-7.20(4H,m) .

Preparation 5

Preparation of 2-(pyrrol-l-ylcarbonyl)-cyclohexene-l-carboxylic acid.

Pyrrole (1.05ml) was added dropwise to a stirring suspension of 3,4,5,6- tetrahydrophthalic anhydride (2.21g) and sodium hydride (0.61g of a 602 oil dispersion) in anhydrous toluene (40ml) at room temperature under a nitrogen atmosphere. After the initial effervescence had subsided, the mixture was heated to reflux for 2 hours. After cooling, ice/water (50ml) was added cautiously. The aqueous layer was separated and the organic phase re-extracted with water (x2) . The combined aqueous phases were acidified to pH 1-2 and extracted with dichloromethane (x3). Combined dichloromethane layers were washed with brine, dried over sodium sulphate and evaporated to a tan solid, yield 2.89g. This was sufficiently pure to use directly in the preparation of Compound 15. A small amount was recrystallised from ethyl acetate/hexane to give pale tan needles, m.p.

132-133°C. ¹H NMR (CDClg): δ 7.14(2H,br s); 6.28(2H,t); 2.43(4H,br s);

1.74(4H,br t) .

Preparation 6

Preparation of 2-(pyrrol-l-ylcarbonyl)-cyclopentene-l-carboxylic acid.

By a method similar to that described in Preparation 5, but using l-cyclopentene-l,2-dicarboxylic acid anhydride (2.00g), pyrrole (1.05ml), toluene (40ml) and sodium hydride (0.61g of a 602 oil dispersion), the title compound was prepared, yield 2.01g. H NMR (CDC1 ) : δ 7.18(2H,br s);

6.31(2H,t); 2.95-2.86 (2H,m) ; 2.84-2.75(2H,m) ; 2.12(2H,p).

Preparation 7

Preparation of 3.6-dichloro-2-(pyrrol-l-ylcarbonyl)benzoic acid.

The title compound was prepared by a method similar to that described in

Preparation 5, but using 3,6-dichlorophthalic anhydride (5.0g), pyrrole (1.67ml), toluene (80ml) and sodium hydride (0.97g of a 602 oil dispersion), yield 4.0g. This was sufficiently pure to use directly in the preparation of Compound 16. A small amount (l.Og) was recrystallised from ethyl acetate/hexane to give a pale tan solid, yield 0.32g, m.p 133-135°C (dec). ¹H NMR (CDC1 ) : δ 7.57(lH.d); 7.53(lH,d); 6.59(lH,br m) ; 6.35(3H, br m) .

Preparation 8

Preparation of 2-fluoro-6-(pyrrol-1-ylcarbonyl) benzoic acid and 3-fluoro-2-(pyrrol-l-ylcarbonyl)benzoic acid.

By a method similar to that described in Preparation 5, but using 3-fluorophthalic anhydride (5.0g), pyrrole (2.08ml), toluene (60ml) and sodium hydride (1.20g of a 602 oil dispersion) the title compound was prepared. The mixture of title compounds was obtained as a brown gummy solid, yield 4.3g, containing 1 mole of ethyl acetate. H NMR (CDC1,): (shows an approximate 1:1 ratio of regioisomers) : δ 7.92 (lH,d); 7.67-7.56(3H,m); 7.48-7.30(4H,m) ; 7.10(2H, br s); 6.30(4H m, br s). (Individual component assignments uncertain). Preparation 9

Preparation of 2-(pyrrol-l-ylcarbonyl)-3,4,5-trimethoxy benzoic acid and 2-( yrrol-1-ylcarbonyl)-4,5,6-trimethoxybenzoic acid.

The title compounds were prepared by a method similar to that described in Preparation 5, but using 3,4,5-trimethoxyphthalic anhydride (7.0g), pyrrole (2.03ml), toluene (60ml) and sodium hydride (l.lβg of a 602 oil dispersion) . The mixture of title compounds was obtained as a dark red oil, yield 8.8g, containing 1.5 moles of ethyl acetate. H NMR (CDC1-): (shows an approximate 2:1 ratio of regioisomers): δ 7.47(lH,s, major component), 7.38(lH,s minor component); 7.10(2H,br s major component); 6.83(2H,br s, minor component); 6.38(2H, t, major and minor components); 4.1-3.8 (9H,3S, major and minor components). Preparation 10

Preparation of 2-(pyrrol-2-ylcarbonyl)-pyridine-3-carboxylic acid. Pyrrole (4.63ml) in tetrahydrofuran (25ml) was added dropwise to ethylmagnesium bromide (22.3ml of a 3.0 molar solution in ether) in tetrahydrofuran (30ml) at room temperature under an atmosphere of nitrogen. Addition was controlled to maintain a gentle reflux of the solvent. After hour, a slurry had developed and the reaction had cooled back to room temperature. 2,3-Pyridinedicarboxylic acid anhydride (5.0g) in tetrahydrofuran (40ml) was added dropwise. A bright yellow solid replaced the slurry. Stirring was continued for a further 1 hour at room temperature. Ether (50ml) was added and the solid was filtered off under suction, washing with ether. This solid was dissolved in water and cooled to 0°C before acidification to pH 2 with IN hydrochloric acid. The resulting mixture was extracted with ethyl acetate (x5) and the combined organic phases were washed with brine (x2), dried over sodium sulphate and evaporated to a tan foam. Recrystallisation from ethyl acetate (x3) gave the pure title compound as a tan solid, yield 2.03g, m.p. 91°C (dec), contains 0.33 mole of ethyl acetate. H NMR (do.DMSO): δ 13.33(1H, br s);

12.04(1H, br s); 8.71(lH,dd); 8.21(lH,dd); 7.59(lH,dd); 7.14(1H, br m) ; 6.1K1H, br m) ; 6.13(lH,q). Preparation 11

Preparation of 4-(pyrrol-2-vlcarbonyl)-pyridine-3-carboxylic acid. By a method similar to that described in Preparation 10, but using 3,4-pyridinedicarboxylic acid anhydride (5.0g), pyrrole (4.63ml), ethylmagnesium bromide (22.3ml of a 3.0 molar solution in ether) and tetrahydrofuran (115ml), the title compound was obtained as a grey solid, yield 3.1g, m.p 130°C (dec), contains 0.25 mole of ethyl acetate. H NMR (dgDMSO): δ 13.60(1H, br s); 12.32(lH,br s); 9.19(lH,s); 8.97(lH,d); 7.63(lH,d); 7.36(1H, br ) ; 6.50(lH,br m) ; 6.34(lH,m). Preparation 12

Preparation of 3-(pyrrol-2-ylcarbonyl)-pyrazine-2-carboxylic acid. Pyrrole (0.94ml) in tetrahydrofuran (25ml) was added dropwise to a solution of ethylmagnesium bromide (4.53ml of a 3.0 molar ether solution) in tetrahydrofuran (15ml) under an atmosphere of nitrogen. The addition rate was controlled so as to maintain a gentle reflux. After 30 minutes, a solution of 2,3-pyrazinedicarboxylic acid anhydride (1.02g) in tetrahydrofuran (40ml) was added via cannula. The resulting dark brown solution was stirred for 4 hours at room temperature. The solvent was evaporated and the residue taken up in ice water (100ml), washed with ether/hexane (50ml of a 1:1 mixture) and acidified to pH 2 with IN hydrochloric acid. The mixture was extracted with ethyl acetate (x4) . The combined organic layers were washed with brine, dried over sodium sulphate and evaporated to give the title compound as a brown residue, yield 1.40g. ¹H NMR (CDC1₃): δ 9.95 (1H, br s); 8.88(lH,d); 8.78(lH,d); 7.24(lH,br m) ; 6.76(lH,br m) ; 6.34(lH,br m) . Preparation 13

Preparation of 2- (3 , 4-dimethylpyrrol-2-ylcarbonyl )pyridine-3-carboxylic acid.

By a method similar to that described in Preparation 12, but using

2,3-pyridinedicarboxylic acid anhydride (1.57g), ethyl magnesium bromide

(7.01ml of a 3.0 molar solution in ether), 3,4-dimethylpyrrole (2.0g, prepared according to the method of Ichimura et. al. Bull. Chem. Soc. Jpn. ,

49,pp 1157-1158, 1976) and tetrahydrofuran (100ml) the title compound was obtained after purification by recrystallisation from ethyl acetate (x3), yield 0.203g. ¹H NMR (d, DMSO) : ό 8.89(lH,d); 8.43(lH,d); 7.76(lH,dd); o

7.01(lH,d); 2.04(3H,s); 1.73(3H, br s).

EXAMPLE 1

Preparation of Compound 1

Pyrrole (3.45ml) was dissolved in dry tetrahydrofuran (90ml) under a nitrogen atmosphere and cooled to -70°C. A solution of n-butyllithium in hexane (20ml of a 2.5 molar solution) was added dropwise such that the temperature did not rise above -60°C. 3,4-diethoxycyclobut-3-en-l,2-dione

(8.5g) in dry tetrahydrofuran (10ml) was added and the reaction mixture allowed to warm to -25°C to effect complete dissolution. The solution was cooled again to -70°C and trimethylsilyl chloride (6.34ml) added. The reaction mixture was allowed to warm to room temperature, stirred for k hour then quenched with saturated aqueous sodium bicarbonate solution. The aqueous layer was separated and the organic phase diluted with diethylether, washed with brine (2x100ml) and then dried over sodium sulphate. Removal of solvent yielded 2,3-diethoxy-4-(N-pyrrolyl)

-4-trimethylsilyloxy-cyclobut-2-en-l-one as a dark oil, yield 12.6g.

3 The crude oil was dissolved in xylene (100cm ) and heated under reflux for 3 hours, then allowed to cool. A solution of ferric chloride (15g) in water (75ml) was added and stirred for 3 hours. The resultant suspension was filtered through hyflo, washed with diethyl ether and the aqueous and organic layers separated. The organic phase was washed with water, dried over magnesium sulphate and solvent removed in vacuo to yield a red oil.

Compound 1 was separated from this oil by chromatography and purified by trituration with hexane (x3). The product was a red oil, yield 1.2g. ^λE NMR data (CDC1₃): δ 7.53(lH,dd); 7.10(lH,dd); 6.36(lH,t); 4.42(2H,q);

4.31(2H,q); 1.41(6H,2t). EXAMPLE 2 Preparation of Compound 14

Compound 14 was prepared following the method of Yerxa and Moore (Tetrahedron Letters, Vol. 33, No. 51 pp 7811-7814, 1992).

EXAMPLE 3 Preparation of Compound 13

Pyrrole (1.04ml) was dissolved in dry tetrahydrofuran (25ml) under a nitrogen atmosphere and cooled to -78°C. A solution of n-butyllithium in hexane (6.0ml of a 2.5 molar solution) was added dropwise. 3,4-Diisopropoxycyclobut-3-en-l,2-dione (2.97g) in dry tetrahydrofuran (10ml) was added and the mixture was stirred at -78°C for 45 minutes before adding trimethylsilyl chloride (1.89ml). The reaction was stirred at -78°C for 15 minutes. The reaction was quenched with saturated aqueous sodium bicarbonate solution (50ml). The aqueous layer was separated and the organic phase diluted with diethylether (100ml), washed with brine (x2) and then dried over sodium sulphate. Removal of solvent yielded the crude 2,3-diisopropoxy-4-(N-pyrrolyl)-4-trimethylsilyoxycyclobut-2-en-l-one as a dark oil, yield 4.7g.

The crude oil was dissolved in xylene (200ml) and heated under reflux for 5 hours. After cooling, the reaction mixture was washed with a solution of ferric chloride (lOg) in methanol/water (80ml of a 1:1 mixture) (x3), brine (x2), and dried over sodium sulphate. Chromatography of the red oil on silica, eluting with ethyl acetate in hexane (10:90) gave a yellow solid. Recrystallisation from hexane/dichloromethane gave Compound 13 as bright yellow crystals, yield 0.47g, m.p 54.5-55.5°C. H NMR (CDC1₃): δ 7.53(lH,t); 7.08(lH,dd); 6.36(lH,t); 5.03(1H, hept); 4.82(1H, hept) ; 1.35(12H,t) .

EXAMPLE 4 Preparation of Compound 20 By a method similar to that described in Example 3 but using 3-isopropoxy-4-methylcyclobut-3-en-l,2-dione (prepared as described in Preparation 1 ) (2.26g), pyrrole (1.01ml), n-butyllithium (5.84ml of a 2.5 molar solution in hexane) and trimethylsilylchloride (1.84ml) to give 2-isopropoxy-3-methyl-4-(N-pyrrolyl)-4-trimethylsilyloxycyclobut-2-en-l-one as a dark oil, yield 3.5g. This was heated to reflux in xylene (200ml) for 16 hours and worked up as described in Example 3. The crude material was filtered through a pad of silica, washing first with hexane and then diethyl ether. Evaporation of the filtrate gave the pure Compound 20 as a pale brown oil which solidified, yield 0.932g, m.p 36-41 °C. H NMR (CDC1₃): δ 7.51(lH,dd); 7.08 (lH.dd); 6.37(lH,t); 4.93(lH,hept) ; 2.04(3H,s); 1.38(6H,d).

EXAMPLE 5 Preparation of Compound 22 By a method similar to that described in Example 3 but using 3-chloro- -4-methoxycyclobut-3-en-l,2-dione (prepared according to the method of Ohno, Yamamoto, Shirasaki and Eguchi, J. Chem.Soc. Perkin Trans 1, pp 263-271, 1993) (2.55g), pyrrole (1.20ml), n-butyllithium (6.95 ml of a 2.5 molar solution in hexane and trimethylsilylchloride (2.20ml) to give 2-chloro-3-methoxy-4-(N-pyrrolyl)-4-trimethylsilyloxycyclobut-2-en-l-one as a dark brown oil. This was dissolved in xylene (150ml) and heated under reflux for 2 hours followed by work up as described in Example 3. Flash chromatography of the crude product on silica, eluting with ethyl acetate/hexane (1:4), followed by recrystallisation from ethyl acetate/hexane gave the title compound as golden crystals, yield 0 0..226611gg,, mm..pp.. 112211--112277°°CC. ^XH NMR (CDC1,): δ 7.75(lH,dd); 7.21(lH,dd); 6.44(lH,t); 4.26(3H,s)

EXAMPLE 6 Preparation of Compound 23

By a method similar to that described in Example 3 but using 3-chloro-4-isopropoxycyclobut-3-en-l,2-dione (prepared as described in Preparation 2 above) (1.65g), pyrrole (0.65ml), n-butyllithium (3.78ml of a 2.5 molar solution in hexane) and trimethylsilylchloride (1.19ml), to give 2-chloro-3-isopropoxy-4-(N-pyrrolyl)-4-trimethylsilyloxycyclobut-2-en-l-one as a dark brown oil. This was dissolved in xylene (150ml) and heated under reflux for 3 hours followed by work up as described in Example 3. Flash chromatography of the crude product on silica eluting with ethyl acetate/hexane (3:17), followed by recrystallisation from ethyl acetate/hexane gave the title compound as a yellow/brown microcrystalline solid, yield 0.149g, m.p 73-75°C. ^""^"H NMR (CDC1₃): δ 7.66(lH,dd); 7.20(lH,dd); 6.43(lH,t); 5.16(lH,hept) ; 1.43(6H,d).

EXAMPLE 7 Preparation of Compound 8

By a method similar to that described in Example 3 but using 3,4-dimethoxycyclobut-3-en-l,2-dione (2.0g), 3, -dimethylpyrrole (prepared according to the method of Ichimura et al., Bull. Chem. Soc, Jpn., 49, pp 1157-1158, 1976) (1.34g), n-butyllithium (5.64ml of a 2.5 molar solution in hexane) and trimethylsilylchloride (1.78ml) to give 2,3-dimethoxy-4-(N-3, - dimethylpyrrolyl)-4-trimethylsilyloxycyclobut-2-en-l-one as an orange/brown oil. This was dissolved in xylene (100ml) and heated under reflux for 16 hours and worked up as described in Example 3. The crude material was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (3:17), followed by recrystallisation from dichloromethane/hexane to give the title compound as a yellow crystalline solid, yield 0.048g, m.p. 103-107°C. ^λE NMR (CDC1₃): δ 7.26(lH,s); 4.10(3H,s); 4.03(3H,s); 2.35(3H,s); 2.00(3H,s).

EXAMPLE 8

Preparation of Compound 35 By a method similar to that described in Example 3 but using 3-methoxy-4- -phenylthiocyclobut-3-en-l,2-dione (prepared as described in Preparation 3) (2.70g), pyrrole (0.85ml), n-butyllithium (4.91ml of a 2.5 molar solution in hexane) and trimethylsilylchloride (1.55ml) to give 2- -methoxy-3-phenylthio-4-(N-pyrrolyl)-4-trimethylsilyloxycyclobut-2-en-l-one as a brown oil. This was dissolved in xylene (100ml) and heated to 120°C for 1 hour and then at 140°C for 1 hour. The reaction was worked up as described in Example 3. The crude material was purifid by flash chromatography on silica, eluting with ethyl acetate/hexane (1:4), followed by recrystallisation from ethyl acetate/hexane to give the title compound as a brown solid, yield 0.660g, m.p. 76-78°C. ¹H NMR (CDC1₃): δ 7.54(lH,m); 7.46(2H,m); 7.31(3H,m); 7.11(lH,dd); 6.39(lH,t); 3.83(3H,S).

EXAMPLE 9

Preparation of Compound 38 By a method similar to that described in Example 3 but using 3,4-diphenoxycyclobut-3-en-l,2-dione (prepared as described in Preparation 4) (1.34g), pyrrole (0.35ml), n-butyllithium (2.01ml of a 2.5 molar solution in hexane) and trimethylsilylchloride (0.64ml), 2, -diphenoxy-4-(N-pyrrolyl)-4-trimethylsilyloxycyclobut-2-en-l-one was prepared as a dark oil. This was dissolved in xylene (100ml) and heated to reflux for 18 hours, followed by work up as described in Example 3. The crude material was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (1:4) followed by three recrystallisations from ethyl acetate to give the title compound as a green/brown solid, yield 0.096g, m.p. 216-219°C. ¹H NMR (CDCl_j): δ 7.60(lH,dd); 7.29-7.18(6H,m) ; 7.10-7.01(2H,m) ; 6.94-6.86(3H,m) ; 6.46(lH,t). EXAMPLE 10

Preparation of Compound 49

A solution of dimethyldioxirane (5.82ml of a 0.095 molar solution in acetone, prepared according to the method of Adam, Chan, Cremer, Gauss, Scheutzow and Schindler, J. Org. Chem, 52, 2800, 1987) was added in one portion to a solution of Compound 35(0.078g) in dry acetone (5ml) at 0°C. The reaction mixture was allowed to warm to room temperature overnight. After evaporation of the solvent, nmr of the crude material showed a mixture of the sulphoxide and sulphone. This material was re-submitted to the reaction conditions, using a further quantity of dimethyldioxirane (1.2ml of a 0.095 molar solution). After stirring overnight at room temperature, the solvent was evaporated and the residue recrystallised from ethyl acetate to give an orange crystalline solid, yield 0.043g, m.p. 147-150°C. ^λ NMR (CDC1₃): δ 8.10(2H,d); 7.65(lH,t); 7.57(2H,d); 7.51(lH,m); 7.08(lH,d); 6.44(lH,t); 4.41(3H,s).

EXAMPLE 11 Preparation of Compound 2

Compound 2 was prepared following the method of Comforth and Ming-hui (J. Chem. Soc. Perkin Trans I, 1463, 1990).

EXAMPLE 12 Preparation of Compound 15

Phosphorous oxychloride (2ml) was added to a solution of 2-(pyrrol-l-ylcarbonyl)cyclohexene-l-carboxylic acid (prepared as described in Preparation 5 ) (2.00g) in dry pyridine (20ml) at room temperature under an atmosphere of nitrogen. The solution became hot and the colour darkened. After 2 hours the reaction was poured into water and extracted with ether (x3). The combined organic layers were washed with water, brine and dried over sodium sulphate. Evaporation gave a dark red oil which was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (3:17) to give a yellow solid. This was re-crystallised from ether/hexane to give orange/yellow crystals of the title compound, yield 0.395g, m.p 108.5-111°C. ^XH NMR (CDC1₃): δ 7.55(lH,dd); 7.10(lH,dd); 6.35(lH,t); 2.63-2.50(4H,m) ; 1.80-1.68(4H,m) .

EXAMPLE 13 Preparation of Compound 17

Compound No. 17 was prepared by a method similar to that described in Example 12, but using 2-(pyrrol-l-ylcarbonyl)cyclopentene-l-carboxylic acid (prepared as described in Preparation 6) (2.00g), pyridine (20ml) and phosphorous oxychloride (2ml). The crude product was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (3:17) to give a yellow crystalline solid which was washed with hexane to give the pure title compound, yield 0.311g, m.p. 158-159°C (dec). ¹H NMR (CDCl_j): δ 7.54(lH,dd); 7.10(lH,dd); 6.34(lH,t); 2.98-2.85(4H,m) ; 2.13(2H,p).

EXAMPLE 14

Preparation of Compound 16 By a method similar to that described in Example 12 but using 3,6-dichloro-2-(pyrrol-l-ylcarbonyl)benzoic acid (prepared as described in Preparation 7) (3.0g), pyridine (30ml) and phosphorous oxychloride (3ml). The crude product was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (3:17) followed by recrystallisation from cyclohexane to give fine yellow needles of the title compound, yield 0.046g, m.p. 179-180°C. ¹H NMR (CDC1₃): δ 7.75(lH,dd); 7.66(lH,d); 7.65(lH,d); 7.30(lH,dd); 6.54(lH,t).

EXAMPLE 15

Preparation of Compounds 18 and 19 Compounds 18 and 19 were prepared by a method similar to that described in Example 23 but using a mixture of 3-fluoro-2-(pyrrol-l- -ylcarbonyl)benzoic acid and 2-fluoro-6-(pyrrol-l-ylcarbonyl)benzoic acid (prepared as described in Preparation 8) (4.3g), pyridine (30ml) and phosphorous oxychloride (3ml) . The crude product was purified by flash chromatography on silica, eluting with ethyl acetate/hexane (3:17) to give a mixture of the title compounds as fine yellow needles. Gas chromatographic anaylsis showed a 11:9 mixture of regioisomers, yield 0.421g. ¹H NMR (CDC1 ) : δ 8.22(lH,d,major component) 8.14(lH,d, minor component); 7.84-7.70(2H,m, major and minor components); 7.50 (lH.t, minor component); 7.48(lH,t, major components); 7.33(lH,m, major and minor components); 6.53(lH,t, major & minor components).

EXAMPLE 16 Preparation of Compound 21 Compound No. 21 was prepared by a method similar to that described in Example 12 but using a mixture of

2-(pyrrol-l-ylcarbonyl)-3,4,5-trimethoxybenzoic acid and

2-(pyrrol-l-ylcarbonyl)-4,5,6-trimethoxybenzoic acid (prepared as described in Preparation 9) (5.0g), pyridine (40ml) and phosphorous oxychloride (4ml). The crude product was purified by flash chromatography on silica, eluting with ethyl acetate/dichloromethane/hexane (6:1:13), following by repeated recrystallisation from ethyl acetate (X5) gave the title compound as a yellow crystalline solid, yield 0.136g, m.p. 200-201°C. H NMR (CDC1₃): δ 7.74(lH,s); 7.66(lH,dd); 7.22(lH,dd); 6.46(lH,t); 4.05(3H,s); 4.01(3H,s); 3.98(3H,s).

EXAMPLE 17

Preparation of Compound 3 Compound 3 was prepared following the method of Comforth and Ming-hui (J. CHem. Soc. Perkin Trans I, 1463, 1990).

EXAMPLE 18 Preparation of Compound 24 A solution of 2-(pyrrol-2-ylcarbonyl)pyridine-3-carboxylic acid (1.50g, prepared as described in Preparation 10) in acetic anhydride (30ml) was heated to 85°C under a nitrogen atmosphere for 24 hours. After cooling the solvent was removed in vacuo, keeping the water bath temperature below 50°C. The black residue was applied to a silica chromatography column, eluting with ethyl acetate/hexane (3:2) and then ethyl acetate/dichloromethane/hexane (8:1:2) to give a yellow crystalline product. Recrystallisation from chloroform and a further purification by flash chromatography on silica, eluting with the same solvent system mentioned above, gave the title compound as yellow microcrystals, yield 0.404g, m.p. 269-271°C. ¹H NMR (CDClg): δ 9.11(lH,dd); 8.68(lH,dd); 7.80(lH,dd); 7.73(lH,dd); 7.47(lH,dd); 6.58(lH,t).

EXAMPLE 19 Preparation of Compound 25 Compound No. 25 was obtained by a method similar to that described in Example 18, but using 4-(pyrrol-2-ylcarbonyl)pyridine-3-carboxylic acid (0.35g, prepared as described in Preparation 11) and acetic anhydride (30ml). The crude product was purified by flash chromatography on silica, eluting with chloroform/ethyl acetate (1:9) to give the pure title compound as a bright yellow solid, yield 0.275g, m.p. 185-186°C. H NMR (CDC ): δ 9.59(lH,s); 9.13{lH,d); 8.06(lH,d); 7.83(lH,dd); 7.42(lH,dd); 6.60(lH,t).

EXAMPLE 20 Preparation of Compound 31 A solution of 3-(pyrrol-2-ylcarbonyl)pyrazine-2-carboxylic acid (1.40g, prepared as described in Preparation 12) in acetic anhydride (25ml) was heated to 85°C for 5 hours under a nitrogen atmosphere and then left to cool to room temperature overnight. The black precipitate which appeared was filtered under suction and purified by dissolving in hot ethyl acetate, filtering insolubles and evaporating the filtrate to give the pure title compound as an olive green powder, yield l.Olg, m.p. 311-315°C. H NMR (d^DMSO): δ 9.01(lH,d); 8.99(lH,d); 7.88(lH,dd); 7.30(lH,dd); 6.60(lH,t).

D

EXAMPLE 21

Preparation of Compound 27

A suspension of Compound 24 (0.275g, prepared as described above) in tetrahydrofuran (15ml) containing methyl iodide (10ml) was heated to reflux for 2 hours. Chloroform (10ml) was added to aid solubility and heating was continued for a further 70 hours. During this time a precipitate appeared.

This was filtered under suction, washing with tetrahydrofuran and then ether to give the title compound as a brick red solid, yield 0.105g, m.p.

205°C (dec). ¹H NMR ( do. DMSO) : δ 9.47(lH,br m) ; 9.41(lH,d); 8.56(lH,br m) ;

8.15(lH,br s); 7.65(lH,br s); 6.89(lH,br s); 4.78(lH,br s).

EXAMPLE 22 Preparation of Compound 26 By a method similar to that described in Example 21 above, but using Compound 25 (0.275g, prepared as described in Example 19), tetrahydrofuran (15ml) and methyl iodide (10ml), heated at reflux for 16 hours. The title compound was obtained as a brick red solid, yield 0.268g, m.p. 261-263°C (dec), ^""Ή NMR (dgDMSO): δ 10.04(lH,s); 9.53(lH,br d) ; 8.77(lH,d); 8.24(lH.br s); 7.71(lH,br s); 6.95(lH,t); 4.70(3H,br s).

EXAMPLE 23 Preparation of Compound 32 Compound No. 23 was prepared by a method similar to that described in Example 21 above, but using Compound 51(0.031g, prepared as described in Example 36 below), tetrahydrofuran (15ml) and methyl iodide (5ml) heated under reflux for 120 hours. The title compound was obtained as a brick red solid, yield 0.041g, m.p. 183°C (dec). ¹H NMR (d_gDMS0): δ 9.34(lH,d); 9.25(lH,d); 8.42(lH,dd); 7.80(lH,s); 4.66(3H,s); 2.40(3H,s); 2.05(3H,s).

EXAMPLE 24

Preparation of Compounds 29 and 30 Compound 24 (0.120g, prepared as described in Example 18) was dissolved in 982 sulphuric acid (1ml) at 0°C. A solution of potassium nitrate (0.180g) in 98Z sulphuric acid (1ml) was added dropwise. The dark brown solution was stirred for 20 minutes, poured into ice and the acid quenched with solid sodium hydrogen carbonate to pH7. The mixture was extracted with ethyl acetate (x4). The combined organic layers were washed with brine, dried over sodium sulphate and evaporated to give the title compounds as a tan solid, yield 0.140g, as a 2:1 mixture of Compounds 29 and 30. H NMR (CDC1 ) : δ 9.20 (lH,m, major & minor components); 8.75 (lH,dd, minor component); 8.69(lH.dd, major component); 8.50(lH,d, minor component); 7.86-7. 9(m,lH of major component, 2H of minor component); 7.36(lH,d, major component); 7.18(lH,d, major component).

EXAMPLE 25 Preparation of Compound 28 A solution of 2-acetylpyrrole (2.20g) in tetrahydrofuran (30ml) was added dropwise to a suspension of sodium hydride (1.21g of a 602 oil dispersion) in tetrahydrofuran (30ml) at room temperature under a nitrogen atmosphere. After 30 minutes, diethyloxalate (5ml) was added in one portion. The mixture was stirred at room temperature for 16 hours and then heated under reflux for a further 24 hours. The solid sodium salt of the title compound precipitated as an orange solid. This was filtered under suction, washing with ether. It was possible to store this salt protected from oxygen at 0°C with no apparent decomposition. In order to prepare the free title compound, the salt was dissolved in water, acidified to pH2, saturated with sodium chloride and extracted with ethyl acetate (x5). The solvent was evaporated and the residue recrystallised from ethyl acetate to give the title compound as fine yellow needles, yield 1.95g, m.p.

159-163°C. ¹H NMR (do.DMSO) : δ 7.55(lH,dd); 6.86(lH,dd); 6.38(lH,t);

5.82(lH,s) .

EXAMPLE 26

Preparation of Compound 33

N-chlorosuccinimide (0.203g) was added in one portion to a solution of

Compound 28 (0.225g, prepared as described in Example 25) in tetrahydrofuran (20ml) at room temperature. After 2 hours, the solvent was evaporated and the residue was purified by flash chromatography on silica, eluting with methanolethyl acetate (3:17). The red solid obtained was heated with ethyl acetate (50ml) to remove soluble impurities, filtered and washed with ethyl acetate to give the title compound as an orange/red solid, yield 0.161g, m.p. >310°C. ^λ NMR (d, DMS0):δ 7.34(lH,dd);

1 ⁶

6.55(lH,dd); 6.25(lH,t). H NMR also shows the presence of 1/3 mole of ethyl acetate of crystallisation.

EXAMPLE 27

Preparation of Compounds 36, 34 and 60. The sodium salt of Compound 28 (3.60g, prepared as described in Example 25 or alternatively prepared by addition of 1 equivalent of sodium hydride, as an oil dispersion to Compound 28 in dimethylformamide) was suspended in dimethylformamide (40ml) and methyliodide (5ml) followed by 15-crown-5 (0.10ml) were added. The mixture was stirred at room temperature under a nitrogen atmosphere for 48 hours. A further quantity of methyl iodide (5ml) was added and the mixture heated to 50°C for 4 hours, before cooling and pouring into ice/water (200ml). The aqueous mixture was extracted with ethyl acetate (x5) and the combined organic layers dried over sodium sulphate and evaporated to a brown solid. The components were separated by flash chromatography on silica, eluting with ethyl acetate/hexane (1:4). The first component to be eluted was Compound 36 as a yellow solid, yield 0.048, m.p. 106-109°C.

^XH NMR (CDC1 ): δ 7.52(lH,dd); 7.08(lH,dd); 6.38(lH,t); 4.09(3H,s); 2.04(3H,s).

The next component to be eluted was recrystallised from ethyl acetate (X2) to give Compound 34 as yellow crystals, yield 0.98g m.p. 190-191°C. H NMR (CDC1₃): δ 7.57(lH,dd); 7.09(lH,dd); 6.42(lH,t); 6.01(lH,s); 3.91(3H,s). The recrystallisation residues and the remaining mixed fractions from the silica chromatography were combined. A further separation on silica, eluting with methanol/dichloromethane (1:19) gave the third component (which was very close to the second component). Recrystallisation from ethyl acetate (x2) gave Compound 60 as bright orange needles, yield 0.145g, m.p. 183-186°C. ^XH NMR (CDC1 ) : δ 7.63(lH,dd), 6.76(lH,dd), 6.36(lH,t), 5.76(lH,s), 3.95(3H,s).

EXAMPLE 28 Preparation of Compound 39 A suspension of the sodium salt of Compound 28 (0.280g, prepared as described in Example 25) in dimethylacetamide (15ml) was treated with ethylbromoacetate (2ml) and heated to 60°C for 16 hours. After cooling, the mixture was poured into water and extracted with ether (x3). The combined extracts were washed with water (x3), brine and dried over magnesium sulphate. Evaporation of the solvent and purification of the residue by flash chromatography on silica, eluting with ethyl acetate/hexane (1:4), gave a yellow solid. This was recrystallised form ethylacetate to give the title compound as yellow microcrystals, yield 0.058g, m.p. 125-126°C. ^λ NMR (CDC1₃): δ 7.60(lH,dd), 7.10(lH,dd), 6.43(lH,t), 5.88(lH,s), 4.70(2H,s), 4.30(2H,q), 1.33(3H,t). EXAMPLE 29

Preparation of Compound 40

By a similar method to that described in Example 25, but using

2-acetylindole (1.06g, prepared according to the method of Aki oto, Kawai and Nomura, Bull. Chem. Soc. Jpn, 58_,pp 123-130, 1985) diethyloxalate

(3ml), sodium hydride (0.40g of a 602 oil dispersion) and tetrahydrofuran

(40ml). Recrystallisation of the crude material from ethyl acetate gave the title compound as a tan solid, yield 0.52g m.p. 206-209°C.

^XH NMR (do.DMSO): δ 8.24(lH,d), 7.74(lH,d), 7.50(lH,t), 7.34(lH,s),

7.31(lH,t), 5.95(lH,s).

EXAMPLE 30

Preparation of Compounds 46, 47 and 61 The title compounds were prepared by a method similar to that described in Example 27, but using Compound 40 (0.710g, prepared as described in Example 29), methyl iodine (10ml), sodium hydride (0.16g of a 602 oil dispersion), dimethylformamide (10ml) and 15-crown-5 (3 drops), which were stirred at room temperature for 7 days. Separation of the components in the crude product by flash chromatography on silica, eluting with ethyl acetate/dichloromethane/hexane (1:1:3), gave, after crystallisation from ethyl acetate the three title compounds (in order of elution) :

Compound 47 as yellow needles, yield 0.033g, m.p. 158-159°C. H NMR (CDC1 ): δ 8.41(lH,d), 7.70(lH,d), 7.54(lH,t), 7.44(1H,S), 7.33(lH,t), 4.19(3H,s), 2.07(3H,s).

Compound 46 as a yellow solid, yield 0.089g, m.p. 215-219°C. H NMR (CDC1₃): δ 8.45(lH,d), 7.70(lH,d), 7.55(lH,t), 7.44(lH,s), 7.35(lH,t), 6.11(1H,S); 3.95(3H,S).

Compound 61 as bright yellow needles, yield 0.034g, m.p. 213-214°C. ^λ NMR (CDC1₃): δ 8.45(lH,d), 7.63(lH,d), 7.48(lH,t), 7.32(lH,t), 7.13(lH,s), 5.95(lH,s), 3.98(3H,s).

EXAMPLE 31 Preparation of Compound 48 Oxalyl chloride (0.173ml) was added to a suspension of example compound 28 (0.326g, prepared as described in Example 25) in chloroform (15ml) at room temperature under a nitrogen atmosphere. Dimethylformamide (2 drops) was added and immediate evolution of gas was observed. After 40 minutes, the solid had dissolved. The reaction was evaporated to % volume and the residue applied to a silica chromatography column. Elution with ethyl acetate/dichloromethane/hexane (1:1:3) gave the title compound as a yellow solid, yield 0.294g, m.p. 130°C (dec). ^"4. NMR (CDC1₃): δ 7.64(lH,dd), 7.18(lH,dd), 7.07(1H,S), 6.46(lH,t).

EXAMPLE 32

Preparation of Example Compound 43 Compound 2 (0.202g, prepared as described in Example 11 above) and N-bromosuccinimide (0.462g) were dissolved in dimethylformamide (5ml) and stirred at room temperature under a nitrogen atmosphere for 24 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulphate and then evaporated in vacuo. the crude product was purified by flash chromatography on silica, eluting with ethyl acetate to give a yellow solid. Crystallisation from ethyl acetate gave the title compound as a yellow solid, yield 0.181g, m.p. 195°C. ^λE NMR (CDC1₃): δ 8.39(lH,m), 8.26(lH,m), 7.84(2H,m), 7.38(lH,s).

EXAMPLE 33

Preparation of Compounds 43 and 44 By a similar method to that described in Example 32, but using Compound 2 (0.202g, prepared as described in Example 11), N-bromosuccinimide (0.277g) and dimethylformamide (5ml) stirred at room temperature for 4 hours. After work up and crystallisation from ethyl acetate, the title compound was obtained as a yellow solid, as a 6:1 mixture of Compound 44: Compound 43, yield 0.057g.

^XH NMR (CDC1 ) (for the major component): δ 8.39(lH,m), 8.27(lH,m), 7.83(2H,m), 7.31(lH,d), 6.60(lH,d). M.S. shows molecular ions for both components.

EXAMPLE 34 Preparation of Compounds 41 and 42 By a similar method to that described in Example 32 but using Compound 2 (0.208g, prepared as decribed in Example 11), N-chlorosuccinmide (0.176g) and dimethylformide (5ml) stirred at room temperature for 2 days, the title compound was prepared. After work up and crystallisation from ethyl acetate, the title compound was obtained as an orange solid, as a 3:1 mixture of Compound 41 with Compound No. 42 yield 0.044g. H NMR (CDC1₃ for the major component): δ 8.39(lH,m), 8.27(lH,m), 7.83(2H,m), 7.30(lH,d), 6 . 46 ( lH , d ) .

M.S. shows moleculor ions for both components.

EXAMPLE 35 Preparation of Compound 45 By a similar method to that described in Example 24, but using Example Compound 2 (0.202g, prepared as described in Example 11), potassium nitrate (0.114g) and 982 sulphuric acid (3ml). The crude product was recrystallised from ethyl acetate (x2) to give the title compound as a yellow solid, yield 0.027g, m.p. 213°C. ¹H NMR (CDC1₃): δ 8.49(lH,d); 8.42(lH,dd); 8.34(lH,dd); 7.91(2H,m); 7.71(lH,d).

EXAMPLE 36

Preparation of Compound 51

A solution of 2-(3,4-dimethylpyrrol-2-ylcarbonyl)pyridine-3-carboxylic acid (0.198g, prepared as described in Preparation 13) in acetic anhydride (20ml) was heated to 80°C under a nitrogen atmosphere for 16 hours. The solvent was removed in vacuo and the residue purified by flash chromatography on silica, eluting with ethyl acetate to give the title compound as a yellow solid, yield 0.035g. H NMR (CDC1-): δ 9.07(lH,dd); 8.61(lH,dd); 7.67(lH,dd); 7.49(lH,s); 2.53(3H,S); 2.10(3H,s).

EXAMPLE 37 Preparation of Compound 53

Compound 28 (0.489g, prepared as described in Example 25 ) was suspended in chloroform (22ml) and this mixture was treated with oxalyl chloride (0.26ml) at 0°C under a nitrogen atmosphere. Dimethylformamide (2 drops) was added and the mixture allowed to reach room temperature. After 30 minutes, the solvent was evaporated in vacuo to give crude Compound 48 as a green solid. This was dissolved in dry tetrahydrofuran (25ml) under a nitrogen atmosphere and cooled to 0°C. Morpholine (0.284ml) was added slowly and the mixture was allowed to warm to room temperature. After stirring overnight, further morpholine (0.4ml) was added and stirring continued for 3 hours. The reaction mixture was diluted with ether (150ml). Charcoal was added and left to stand for 1 hour, whereupon the mixture was filtered through Hyflo to give an orange solution. Evaporation of the solvent in vacuo followed by purification by preparative silica chromatography, eluting with ethyl acetate/hexane (2:3), gave the title compound as an orange solid, yield 0.045g, m.p. 159-160°C. H NMR (CDC1,): δ 7.54(lH,dd); 7.12(lH,dd); 6.34 (lH.t); 5.61(lH,s); 3.84(4H,t); 3.58(4H,t). EXAMPLE 38 Preparation of Compound 56 By a method and quantities similar to that described in Example 37, but using dimethylamine (0.5ml) in place of morpholine. Compound 56 was prepared. After addition of dimethylamine at 0°C, the reaction mixture was allowed to warm to room temperature, poured into cold water and extracted with ether (x3). The combined extracts were washed with water, brine and dried over magnesium sulphate. Evaporation of the solvent in vacuo followed by purification by preparative silica chromatography, eluting with ether gave the title compound as an orange solid, yield 0.14g, m.p. 1 13388--113399°°CC.. ¹¹HH NNMMRR ((CCDD(C1,): δ 7.53(lH,t); 7.11(lH,dd); 6.30(lH,t); 5.37(lH,s); 3.24(6H,s)

EXAMPLE 39

Preparation of Compound 57 By a method and quantities similar to that described in Example 37, but using butanethiol (0.5ml) in place of morpholine. After addition of the butanethiol to a tetrahydrofuran solution of crude compound 48, the solution was stirred for 10 minutes. Triethylamine (5 drops) was added followed by a further quantity (10 drops) after 15 minutes. After standing overnight, further triethylamine (10 drops) was added, stirred for 15 minutes, then diluted with ether and filtered through hyflo. The filtrate was evaporated and the residue purified by preparative silica chromatography, eluting with ethyl acetate/hexane (2:3) to give the title compound as an orange solid, yield 0.28g, m.p. 115-116°C. H NMR (CDC1₃): 7.57(lH,dd); 7.22(lH,dd); 6.38(lH,t); 6.29(lH,s); 2.81(2H,t); 1.81-68 (2H,m); 1.58-1.44(2H,m) ; 0.97(3H,t).

EXAMPLE 40

Preparation of Compound 54 N.N.N-trimethylethylenediamine (0.266ml) was added dropwise to a solution of Compound 48 (0.180g, prepared as described in Example 31 above) in dry tetrahydrofuran (20ml) at -20°C under a nitrogen atmosphere. After 1 hour at -20°C, the mixture was allowed to warm to room temperature. The solid present was filtered under suction and the filtrate diluted with dichloromethane (50ml) before washing with water (20ml) and drying over sodium sulphate. The solvent was evaporated and the residue purified by flash chromatography on silica, eluting with methanol/ ethyl acetate (3:2) to give a red oil which solidified on standing in the freezer overnight. Trituration with ether/hexane (1:1) gave the title compound as a brown powder, yield 0.085g, m.p. 55-56°C. ^λE NMR (CDC1₃): δ 7.54(lH,dd) ; 7.09(lH,dd); 6.30(lH,t); 5.39(lH,s); 3.88(2H,t); 3.05(3H,s); 2.53(2H,t); 2.25(6H,s) .

EXAMPLE 41

Preparation of Compound 58 The method of Example 40 was repeated, except that the reaction was carried out at -30°C and N-methylpiperazine (0.466ml), Compound 48 (0.364g) and tetrahydrofuran (35ml) were used. The title compound was obtained after work up and silica chromatography as an orange solid, yield 0.402g, m.p. 127-128°C. ¹H NMR (CDC1₃): δ 7.54(lH,dd); 7.12(lH,dd); 6.32(lH,t); 5.62(lH,s); 3.61(4H,t); 2.55(4H,t); 2.34(3H,s).

EXAMPLE 42

Preparation of Compound 55 Compound 54 (0.160g, prepared as described in Example 40 above) was dissolved in tetrahydrofuran at room temperature. Methyliodide (1ml) was added and the solution stirred for 2 hours. A fine precipitate developed. This was filtered, washing with ether to give the title compound as an orange powder, yield 0.231g, m.p. 298°C (dec). ^" NMR (dgDMSO): δ 7.60(1H, br s); 7.11(lH,dd); 6.40(lH,t); 5.50<1H,S); 4.10-4.00(2H,m) ; 3.60-3.50(2H,m); 3.10(9H,s); 2.98(3H,s).

EXAMPLE 43

Preparation of Compound 52 The method of Example 42, was repeated but using Compound 58 (250mg, prepared as described in Example 41 above), methyl iodide (1ml) and tetrahydrofuran (15ml) . The title compound was obtained as a yellow powder, yield 355g m.p. 315^QC (dec). ^""^"H NMR (d_g DMSO) : δ 7.60(1H br s); 7.12(lH,dd); 6.42(lH,t); 5.90(lH,s); 3.94-3.83(4H,m) ; 3.53-3.43(4H,m) ; 3.14(6H,s).

EXAMPLE 44

Preparation of Compound 37 A solution of the salt of Compound 28 (0.185g, prepared as described in Example 25) in dimethylacetamide (25ml), containing 15-crown-5 (3 drops) was treated with methylchloroformate (0.17ml). After 1 hour, the mixture was poured into water (25ml) and extracted with ethyl acetate (x2) . The combined extracts were washed with brine and dried over magnesium sulphate. The solvent was removed in vacuo and the residue purified by flash chromatography on silica, eluting with ethyl acetate/hexane (1:3) to give a yellow solid. Trituration with water gave the title compound as a crystalline yellow solid, yield 0.043g, m.p. 116-117°C. ¹H NMR (CDC1 ) : δ

7.58(lH,dd); 7.18(lH,dd); 6.71(lH,s); 6.70(lH,m); 3.98(3H,s).

Biological Data

The herbicidal activity of the compounds was tested as follows:

Each chemical was formulated by dissolving it in an appropriate amount, dependent on the final spray volume, of a solvent/surfactant blend which comprised 78.2 gm/litre of Tween 20 and 21.8 gm/litre of Span 80 adjusted to 1 litre using methylcyclohexanone. Tween 20 is a Trade Mark for a surface-active agent comprising a condensate of 20 molar proportions of ethylene oxide with sorbitan laurate. Span 80 is a Trade Mark for a surface-active agent comprising sorbitan mono-laurate. If the chemical did

3 not dissolve, the volume was made up to 5cm with water, glass beads were added and this mixture was then shaken to effect dissolution or suspension of the chemical, after which the beads were removed. In all cases, the mixture was then diluted with water to the required spray volume and 22 glycerol and 0.22 Silwett L77 added. If sprayed independently, volumes of

3 3 10cm and 14cm were required for pre-emergence and post-emergence tests

3 respectively; if sprayed together, 20cm was required. The sprayed aqueous emulsion contained 42 of the initial solvent/surfactant mix and the test chemical at an appropriate concentration.

The spray compositions so prepared were sprayed onto young pot plants at a spray volume equivalent to 1000 litres per hectare. Damage to plants was assessed 5 days after spraying by comparison with untreated plants, on a scale of 0 to 9 where 0 is 02 damage, 1 is 1-52 damage, 2 is 6-152 damage, 3 is 16-252 damage, 4 is 26-352 damage, 5 is 36-592 damage, 6 is 60-692 damage, 7 is 70-792 damage, 8 is 80-892 damage and 9 is 90-1002 damage.

The results of the tests are given in Table III below.

TABLE III

COMPD RATE OF NO APPLN kg/ha BV BN GM ZM OS TA PA CA GA AR MI PO IH AT XT AF AM LR SH SV BP PD EC

2 2 2 5 6 5 1 1 2 9 1 9 2 7 5 2 2 5 2 4 5 7 6 2 9

LO

Lπ

3 2 2 9 6 9 3 3 4 9 3 9 2 9 5 4 2 4 5 5 9 6 8 8 9

13 2 7 9 6 9 2 3 5 9 5 9 0 9 5 4 2 4 4 4 9 9 5 6 9

15 2 8 9 8 9 4 5 5 9 4 9 2 9 6 4 3 6 7 5 9 9 8 8 9

17 2 5 6 6 5 4 2 3 9 2 9 2 9 6 2 5 5 5 6 9 9 9 8 9

18/19 2 6 5 6 4 3 2 2 9 2 9 1 9 5 3 2 2 3 3 9 5 7 4 8

20 2 5 9 6 9 2 2 5 9 6 9 3 9 5 3 3 3 5 5 9 9 8 8 9

TABLE III (continued)

C0MPD RATE OF NO APPLN kg/ha BV BN GM ZM OS TA PA CA GA AR MI PO IH AT XT AF AM LR SH SV BP PD EC

21 5 5 6 5 1 1 2 5 3 5 2 4 5 2 2 2 2 3 5 5 5 5 8

22 6 9 9 9 4 5 9 9 5 9 3 9 9 4 5 3 5 5 8 9 9 8 9

24 7 9 6 7 5 3 4 9 3 9 2 9 6 3 3 3 5 2 9 8 5 7 9

25 6 9 6 9 4 5 9 9 5 9 5 9 9 5 5 5 8 6 9 9 8 9 9

26 2 5 7 6 2 3 2 9 2 5 2 7 5 4 4 5 4 4 9 9 9 5 7

27 6 8 8 4 5 - - 5 - 1 5 2 9 7 5 8

28 5 7 6 8 4 2 4 9 2 6 1 4 2 3 4 3 5 2 8 6 8 5 9

TABLE III (continued)

COMPD RATE OF NO APPLN kg/ha BV BN GM ZM OS TA PA CA GA AR MI PO IH AT XT AF AM LR SH SV BP PD EC

29/30 2

31 2 -

33 2 8 0

34 2 5 9 5 8 4 5 5 9 4 9 7 9 9 5 4 6 5 3 9 9 9 9 9

35 2 9 9 7 9 3 5 9 9 3 9 3 9 9 2 5 4 9 4 9 9 9 9 9

41/42 2 6 5 4 5 5

43 2 6 5 6 5 1 1 0 8 2 4 3 7 5 2 2 2 3 5 2 5 5 2 7

TABLE III (continued)

COMPD RATE OF NO APPLN kg/ha BV BN GM ZM OS TA PA CA GA AR MI PO IH AT XT AF AM LR SH SV BP PD EC

43/44 2

LO 00

45 2

46 2

47 2 5 7 2 6 6

48 2 5 8 6 4 2 2 5 9 3 9 2 6 8 4 5 2 4 4 8 9 8 7 7

61 2 5 4 5 9 2 8 7 6 7

TABLE IV

Abbreviations used for Test Plants

BV - Sugar beet

BN - Rape

GM - Soybean

ZM - Maize

OS - Rice

TA - Winter wheat

PA - Polvgonum aviculare

CA - Chenopodium album

GA - Galium aparine

AR - Amaranthus retroflexus

MI - Matricaria inodora

PO - Portulaca oleracea

IH - Ipomoea hederacea

AT - AbutiIon theoohrasti

XT - Xanthium strumarium

AF - Avena fatua

AM - Alopecurus myosuroides

LR - Lolium rigidum

SH - Sorghum halepense

SV - Setaria viridis

BP - Brachiaria platvphylla

PD - Panicum dichotomiflorum

EC - Echinochloa crus-galli

CE - Cyperus esculentus

SP - Sagittaria pygmae

CHEMICAL FORMULAE

(IN DESCRIPTION)

CHEMICAL FORMULAE (IN DESCRIPTION)

(XI)

Claims

1. A herbicidal composition comprising a compound of formula (I);

or a tautomer or a quaternised derivative thereof where Y is a group of formula -CR¹=CR²-CO- and R¹, R², R³, R⁴ and R⁵ are independently selected from hydrogen; optionally substituted alkyl; optionally substituted alkenyl; optionally substituted alkynyl; optionally substituted aryl; optionally substituted aromatic heterocyclic; halo; nitro; cyano; a group OR⁶ where R⁶ is hydrogen or a salt thereof, carboxy or an ester thereof, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aryl; carboxy or a salt, ester or amide derivative thereof; S(O)_nR⁷ where n is 0, 1 or 2 and R⁷ is optionally alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl; NR⁸R⁹ where R⁸ and R⁹ are independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted aryl and R⁹ may additionally be acyl, or R⁸ and R⁹ together with the nitrogen atom to which they are attached form a hleeterocyclic ring; or R¹ and R² and/or any adjacent two of R³, R⁴ and R⁵ together with the carbon atoms to which they are attached form an optionally substituted fused saturated or unsaturated carbocyclic or heterocyclic ring; in combination with a carrier or diluent.

A composition according to claim 1 wherein the compound of formula (I) is a compound of formula (IA):

wherein R¹, R², R³, R⁴ and R⁵ are as defined in claim 1. 3. A composition according to claim 1 or claim 2 wherein in the compound of formula (I), R¹ and R² are selected from hydrogen, optionally substituted alkyl, halo, OR where R⁶ is as defined in claim 1,

S(O)_nR⁷ where n and R⁷ are as defined in claim 1, or NR ⁸R⁹ where R⁸ and R⁹ are as defined in claim 1.

A composition according to any one of the preceeding claims wherein in the compound of formula (I), R³, R⁴ and R⁵ are independently selected from hydrogen, alkyl, halogen or nitro.

A compound of formula (IB)

wherein R¹, R², R³, R⁴ and R⁵ are as defined in claim 1.

A compound of formula (IA) as defined in claim 2 or a tautomer or a quaternised derivative thereo subject to the following provisos:

(a) R¹ and R² do not together form a fused benzo ring;

(b) where R¹ and R² together form a fused aromatic heterocyclic ring, no two of R³, R⁴ and R⁵ form an optionally subtituted fused aromatic carbocylic or heterocylic ring;

(c) where R³, R⁴ and R⁵ are all hydrogen, R¹ and R² together do not form a fused tetrachloro-benzo ring or R² is not NH(C6H5) or R1 and R2 are not both n-butyl;

(d) where R³, R⁴ and R⁵ are all hydrogen and R² is methoxy, R¹ is not methoxy, n-butyl, phenyl, n-butylacetyleno or phenylacetyleno;

(e) where R⁴ and R⁵ form a fused benzo ring, R³ is not carboethoxy.

A compound selected from 3-nitropyrrolo[1,2-b]isoquinoline-5,10-dione, 2-bromopyrrolo(1,2-b]isoquinoline-5,10-dione, 2,3-dibromopyrrolo- [1,2-b]isoquinoline-5,10-dione, 2,3-dichloropyrrolo-(1,2-b]- isoquinoline-5,10-dione and 2-chloropyrrolo[1,2-b]-isoquinoline-5,10-dione.

8. A process for preparing a compound of formula (IA);

where R¹, R², R³, R⁴ and R⁵ are as defined in claim 1, which process comprises either (a) deprotecting and oxidising a compound of formula (III);

where R²⁵ is a protecting group and R¹, R², R³, R⁴ and R⁵ are as defined in claim 1;

or (b) reacting a compound of formula (VII);

where R¹, R², R³, R⁴ and R⁵ are as defined in claim 1, with a dehydrating agent;

(c) dehydrating a compound of formula (IX);

where R¹, R², R³, R⁴ and R⁵ are as defined in claim 1;

and thereafter if desired, converting the compound of formula (IA) to a different such compound by manipulation of substituents R¹, R², R³, R⁴ and R⁵; or

(d) reacting a compound of formula (X);

where R³, R⁴ and R⁵ are as defined in claim 1, with a compound of formula (XI);

where R²⁶ and R²⁷ are independently alkyl groups, in the presence of a base;

and thereafter if desired, converting the compound of formula (IA) to a differ :eeιnt such compound by manipulation of substituents R¹, R², R³, R⁴ and R⁵.

9. A process for preparing a compound of formula (IB)

where R¹, R², R¹, R⁴ and R⁵ are as defined in claim 1, which process comprises alkylation of a compound of formula (IA) where at least one of R¹ or R² is hydroxy, and separating the resultant compound of formula (IB) from the mixture produced; and thereafter if desired, converting the compound of formula (IB) to a different such compound by manipulation of substituents R¹, R², R³, R⁴ and R⁵.

10. A process for killing or controlling unwanted plant species which

process comprises applying to the plant or to the locus thereof, an effective amount of a compound of formula (I) as defined in claim 1.