IE51004B1 - Fungicidal alpha-aryl 1h-1,2,4-triazole-1-ethanols - Google Patents

Description

The present invention relates to a-aryl-lH-l,2,4-triazole-l-ethanols, more particularly a-cycloalkylalkyl-1-αphenyl-lH-l,2,4-triazole-l-ethanols, their use as fungicides and agricultural compositions for facilitating such use. in our co-pending parent application no. 2353/80 we disclose α-aryl-lH-l,2,4-triazole-l-ethanols substituted in the α-position by a C^_galkyl or C3_gOycloalkyl, in which the cycloalkyl may be unsubstituted or substituted by one or two C^^alkyl groups.

In our British application No. 8320874 we disclose 2-aryl-oxiranes substituted in the 2-position of the oxirane ring by t-butyl, branched Cg_galkyl, cyclopropyl, cyclopentyl or cyclohexyl and their use as intermediates for the preparation of compounds of the co-pending application no. 2353/80 referred to hereinabove.

The present invention provides compounds of formula I, R wherein R° is eycloalkylalkyl of 4 to 11 carbon atoms in - 3 which the cyeloalkyl portion is of 3 to 8 carbon atoms and the alkyl portion of 1 to 3 carbon atoms, said cycloalkylalkyl group being optionally substituted by one or two alkyl groups’of 1 to 3 carbon atoms, R is hydrogen, halogen having an atomic number of from 9 to 35, alkyl of 1 to 4 carbon atoms, mono-, di- or tri-haloalkyl of 1 to 4 carbon atoms in which the halo is indepen10 dently an halogen having an atomic number of from 9 to 35, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, or nitro, and R' is hydrogen, halogen having an atomic number of from 9 to 53, alkyl of 1 to 4 carbon atoms, mono-, di- or tri-haloalkyl of 1 to 4 carbon atoms in which the halo is independently an halogen having an atomic number of from 9 to 35, alkoxy of 1 to 4 carbon atoms, mono-, di or tri-haloalkoxy of 1 to 4 carbon atoms in which the halo is independently an halogen having an atomic number of from 9 to 35, alkylthio of 1 to 4 carbon atoms, nitro, -CN, -COOR, or R is hydrogen, alkyl of 1 to 4 carbon atcms, R' is hydrogen, an halogen having an atomic number of from 9 to 17 or alkyl of 1 or 2 carbon atoms, Z is oxygen or sulfur, or R and R' together represent alkylenedioxy of 1 or carbon atoms substituted onto adjacent carbon atoms of the phenyl Ring A, and Y° nnd Υ are independently hydrogen, halogen having an atomic number of from 9 to 35, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.

Halogen atoms having an atomic number of from 9 to 53 are fluoro, chloro, bromo and iodo, such having an atomic number of from 9 to 35 are fluoro, chloro, bromo and those having an atomic number of from 9 to 17 are fluoro and chloro.

When any R or R1· is or includes mono-, di- or trihaloalkyl this is c,g. CF^ The invention also provides processes for the production of compounds of formula I comprising a) reacting a compound of the formula II: II J/0 r,zt R° R' 1 wherein R°, R, F' and R' are as above defined, with a compound of formula III III wherein X is an alkali metal in an inert organic solvent, b) obtaining a compound of formula Iar °H ? - ch2 HOOC R° la wherein R° and R 'are as defined above by oxidation of the CK, group of a compound of formula Ib, CH R\Z-=\ 0H C I R° CH/=N u Ib wherein fi° and R are as defined above, or c) obtaining a compound of formula Ic, R\ __ 0H Y— \ * Ic /=-N CK;Cfl* - Vl AlkOOC wherein R and R° are as defined above and Alk is C^_^alkyl, by esterification of a compound of formula la with an alcohol of formula IV Alk-OH IV wherein Alk is as defined above, or a reactive functional derivative thereof.

The process a) may be carried out at temperatures typically from O°C to 180°, preferably 4O°C to 120°C, in an inert organic solvent of conventional type, e.g. an amide of an organic carboxylic acid such as dimethylformamide. As is conventional, the compound of the formula III is preferably provided by reacting triazole with a strong base such as an alkali metal hydride e.g. sodium hydride, in an inert organic solvent which is conveniently the same solvent which is to be used in process a).

The oxidation according to process b) nay be carried out with the aid of oxidizing agent capable of oxidizing an CH^-group to a COOH group. Suitable oxidizing agents are potassium permanganate, manganese dioxide and the like, preferably potassium permanganate. The reaction is conveniently carried out in aqueous solution. A suitable reaction temperature for process b) is from 20° to 150°C, preferably from 60° to 120°C.

The compounds of formula Ia are depending on the reaction conditions and the recovery’ steps obtained in free form or in salt form (H of COOH substituted by a cation).

Free forms of compounds of formula Ia may be converted into salt forms in conventional manner and vice versa.

The cation of the salt form of compounds of formula la is preferably an agriculturally acceptable cation such as Na+, K+ and The process c) may be carried out in accordance with known esterification procedures for compounds containing a potentially reactive hydroxyl group. The esterification with an alcohol of formula IV is conveniently carried out at a reaction temperature of from 30°c to 80°c, advantageously under anhydrous conditions and in the presence of an acid, such as hydrogen chloride. Suitable solvents for this reaction are inert organic solvents or an excess of the alcohol of formula IV. - 8 Suitable reactive functional derivatives of an alcohol of formula IV are the corresponding diazoalkane, e.g. a diazo alkane of 1 to 3 carbon atoms, or an alkylhalide, particularly a chloride, bromide or iodide. The reaction with a diazoalkane is conveniently carried out under anhydrous conditions in an inert organic solvent. A suitable reaction temperature is then -20°C to +40°C, more usually -5°C to +20°C. For the reaction with an alkylhalide the compounds of formula la are preferably in salt form, e.g. the alkali metal and silver salt form. Such reaction is conveniently carried out in an inert organic solvent at temperatures of from 0°C to 100°C, more usually 40°C to 9O°C.

The reaction product of processes a), b) and c) may be recovered from the reaction mixture in which it is formed by working up by established procedures.

The compounds of formula I wherein R* is other than COOH may be prepared and used in the form of acid addition salt forms. The compounds of formula I are 20ethanol derivatives and can therefore exist in free form and in alternate forms such as an ethanolate salt form, e.g. a sodium ethanolate form, and in metal complex form, e.g. of metals from the groups lb, Ila, lib, Vlb, Vllb and VIII of the periodic table, such as copper and zinc, 25and with anions such as chloride, sulphate, nitrate, carbonate, acetate, citrate, dimethyldithiocarbamate and the like. - 9 Any salt form of compounds of formula I is preferably in the form of an agriculturally acceptable salt form.

The acid addition salt forms, the ethanolate salt 5 form and the metal complex form can be prepared from the corresponding free form in conventional manner and vice versa.

The compounds of formula II may be prepared by reacting a compound of the formula V wherein R°, R, R and R' are as above defined, with the reaction product of a strong base and trimethylsulfcnium iodide which provides a reagent which may be represented by the formula VI VI which process is carried out in an inert organic 15 solvent. This process is a known type reaction for the preparation of epoxy derivatives from ketones.

Many of the compounds of the formula V are known and those which are not known per se may be prepared from known materials by procedures analogous to those known for preparation of the known compounds. 0 4 - 10 The compounds of the formula I are useful as fungicides in combatting phytophathogenic fungi, including particularly powdery mildews and rust fungi, as indicated by standard in vivo and in vitro tests of the type hereinafter illustrated. For such use the compounds of the formula I may be applied to plants, seed or soil in a manner conventional in the use of fungicidal agents.

As will be appreciated, the amount of the compound of the formula I to be applied will vary depending upon known factors such as the particular compound employed, whether the treatment is prophylactic or therapeutic, whether the compound is applied as a foliar spray, a soil treatment or a seed dressing, the species of fungus under treatment and the time of application. However, in general, satisfactory results are obtained when the compound is applied to a crop locus, ‘either on crops or to soil, at a rate of from about 0.005 to 2, preferably about O.Ol to 1 kg (active ingredient)/hectare. The treatment may be repeated as required, e.g. at 8 to 30 day intervals. When employed as a seed dressing, satisfactory results are obtained when the compound is employed at a rate of from about 0.05 to O.5, preferably about 0.1 to 0.3 g/kg seed.

The term soil as used herein is intended to embrace any conventional growing medium whether natural or artificial. - η The invention also provides, as an addirional feature, fungicidal compositions, comprising, as fungicide, a compound of formula I in free form or in agriculturally acceptable salt form and an inert fungicide carrier or diluent. In general, such compositions contain from about 0.0005 to 90, preferably from about 0.1 to 60% by weight of active’ agent. They may be in concentrate form, for dilution down prior to application, or in dilute, ready to apply, form. As examples of particular forms may be given wettable powder, emulsion concentrate, dusting, spraying, granulate and delayed release forms, incorporating conventional carriers and such other diluents and/or adjuvants acceptable in the agricultural art. Application forms of those compositions generally contain between about 0.0005 and 10% by weight of a compound of formula I as active agent. Typical spray suspensions may contain, for example, from 0.0005% to 0.05%, preferably 0.001% to 0.02% by weight of active ingredient. Concentrate forms of compositions for fungicide use generally contain between about 2 and 90%., preferably between about 5 and 70%, by weight of a compound of formula I as active agent.

Emulsion concentrate forms generally contain from about 10 to 70%, preferably about 20 to 60% by weight of active ingredient. Solid, particulate compositions are preferred.

The compositions particularly adapted for spraying preferably include a surfactant such as a liquid poly51004 - 12 glycol ether, a fatty alkyl sulphate or a lignin sulphonate.

In addition to conventional carrier and surfaceactive materials, formulations of the compound I of the invention may also contain further additives with special purposes e.g. stabilizers, deactivators (for solid formulations on carriers with an active surface), agents for improving the adhesion to plants, corrosion inhibitors, anti-foaming agents and colorants.

Moreover, further fungicides, bactericides or other beneficially-acting materials, such as insecticides, may be present in the formulations and are contemplated as further embodiments of this invention.

Examples of the production of fungicide formulations are as follows: a) Wettable powder formulation parts of a compound of formula I, are ground with 2 parts of lauryl sulphate, 3 parts sodium lignin sulphonate and 45 parts of finely divided kaolinite until the mean particle size is below 5 microns. The resulting spray liquor may be applied by foliar spray as well as by root drench application. b) Granulate formulation Onto 94.5 parts by weight of quartz sand in a tumbler mixer is sprayed 0.5 parts by weight of a binder (nonionic tenside) and the whole thoroughly mixed. 5 Parts - 13 by weight of a compound of formula I, are then added and thorough mixing continued to obtain a granulate formulation with a particle size in the range of from 0.3 to 0.7 mm. The granulate may be applied by incorporation into the soil adjacent the plants to be treated. c) Emulsion Concentrate Parts by weight of a compound of formula I, are mixed with 30 parts by weight of iso-octyl phenyl octaglycol ether and 45 parts by weight of a petroleum fraction with a boiling range of 210-280°c (D20:O.92).

The concentrate is diluted with water to the desired concentration. d) Seed dressing 45 Parts of a compound of a compound of formula I, are mixed with 1.5 parts of diamyl phenoldecaglycolether ethylene oxide adduct, 2 parts of spindle oil, 51 parts of fine talcum and 0.5 parts of colorant rhodamin B. The mixture is ground in a contraplex mill at 10,000 rpm until an average particle of less than 20 microns is obtained. The resulting dry seed dressing powder has good adherance and may be applied to seeds, e.g. by mixing for 2 to 5 minutes in a slowly turning vessel. - 14 31004 Fungi against which the compounds of the formula I are indicated to be particularly of interest include by way of illustration the following: A) Basidiomycetes, comprising A.l) those of the Order Uredinales such as those of the genus Uromvces in plants such as beans, e.g. Uromvces appendiculatus. and ornamentals, e.gl Uromvces dianthi, these of the genus Her.lleia in plants such as coffee, e.g. Henileia vastatrix, those of the genus Puccinia in plants such as cereals (e.g. wheat, oats, barley) e.g. Puccinia graminis, Puccinia recondita and Puccinia striiform.is, or ornamentals, e.g. Puccinia nelargoniizonalis and Puce, antirrhini, those of the genus Phakopsora in plants such as soya, e.g. Phakoosora pachyrhizi , those of the genus I-lelam.psora in plants such flax, e.g. Melamosora lini, and those of the genus Tranzschelia, e.g. Tranzschelia pruni in plums; A.2) those of the Order Ustilacinales such as those of the genus Ustilago in plants such as barley, vzheat, corn and sugarcane, e.g. U. maydis on corn and U. nuda on barley, and A. 3) those of the genus Stereum in pip and stone fruit trees, e.g. Stereum purpureum in apple and prune.

B) Ascomycetes, comprising B. l) those of the Order Erysiohales such as those cf the genus Ervsiphe in plants such as cucumber, barley, wheat and sugarbeet, e.g. Ervsiphe gram-inis f.so. tri tier - 15 on wheat and Erysiphe cichoraceareum on cucumbers; those of the genus Soohaerotheca on cucumbers and roses, e.g. Spohaerotheca panr.osa on roses; those of the genus Podosphaera in apples, pears and prunes, e.g. Podosohaera leucotricha on apples; those of the genus Uncinula on plants such as grapes, e.g. Uncinula necator on grapevines; those of the genus Oidiun on a wide variety of plants; r· ant those of the genus Leverllula in plants such as cotton and other Malvaceae, e.g. Leverllula taurica on cotton.

C) Oomycetes, comprising C.l) those of the genus Phytophthora spp., e.g. Ph. cactorun, Ph. parasitica and Ph. cinamoml on susceptible plants; and C. 2) those of the genus Aohanomyces in plants such as pea and sugar beet, e.g. Aphanomyces eutelches in sugar beet, and D) Deuteromvcetes, comprising D. l) those of the genus Helminthosporium in plants such as barley and corn, e.g. Helm. Sativum; D.2) those of the genus Septoria in plants such as wheat, tomato and celery, e.g. Seot. tritici in wheat, tomato and celery, e.g. Sept, tritici in wheat; 0,3) those of the genus Rhizoctonia in plants such as cotton and potato, e.g. Rhlz. solan! in cotton; D.4) those of the genus Fusarium sop, e.g. F.oxysporum fspy lycopersici in tomato, F. oxysporum f. sp. vasinfectum in cotton, F. oxysporum f. sp. cubense in banana, - 16 F, solarsi in vegetables, F. culmorun in cereals and Γ. qramlnc-arun in cereals; D.5) those of the genus Thielavioosis in plants such as cotton, tobacco etc., e.g. Thielaviopsis basicola in cotton; D.6) those of the genus Phona in plants such as sugar beet, rape etc. , e.g. Phor.a betae in sugar beet; D.7) those of the genus Piricularia sop., e.g. P.oryzae on rice; and D.8) those of the genus Colletotrichum spp., e.g.

C. linderuthianun in beans.

The following conventional tests are illustrative of the manner by which the fungicidal activity of the compounds of the formula I may be indicated.

Test Method A; In vivo employing bean rust (Uromyces appendiculatus). Phaseolus vulgaris (pole bean plant) is cultivated in a mixture of peat and sand in plastic pots of 6 cm diameter for 9 days. The plants are sprayed with a spray liquor containing O.OOO8 to 0.05% (e.g. at 0.0008%, 0.003%, 0.012% and 0.05%) active ingredient.

Treatment comprises foliar spraying to near run-off or soil drenching (28 ml of spray liquor per pot). After drying, the plants are inoculated with a spore suspension spray (500,000 to 700,000 spores/ml) and incubated for. 7 days in an incubation chamber at 100% relative humidity and 21°. The efficacy of the active agent treatment is - 17 determined by comparing the number of pustules/leaf with that on untreated, similarly inoculated check plants.

Test Method Bs In vivo employing cucumber powdery mildew (Erysiphe cichoracearum). Cucumls satlvus (cucumber) is cultivated in a mixture of peat and sand in plastic pots of 6 cm diameter for 7 days. The plants are sprayed with a spray liquor containing 0.0008 to 0.05% (e.g. at 0.0008%, 0.003%, 0.012% and 0.05%) active ingredient. Treatment comprises foliar spraying to near run-off or soil drenching (28 ml of spray liquor per pot). After drying, the plants are inoculated by dusting then with freshly collected conidia and are then incubated for 7 days in an incubation chamber at 60-80% relative humidity and 25-3O°C. The efficacy of the active ingre15 dient is determined by comparing the degree of fungal attack with that on untreated, similarly inoculated check plants.

Fungi of the aforementioned genera cause considerable damage in agriculture and are difficult to prevent or control.

In addition to combatting such fungi, the compounds of the formula I are indicated to be non-phytotoxic at effective doses in plants subject to such fungi and are further indicated to be of particular interest as also acting to combat fungi by systemic action as determined, for example, in the combatting of Oromyces appendlculatus on beans. - 18 Preferred compounds of the formula I have one or more and preferably all of the following features: a) R° is cycloalkylmethyl in which the cycloalkyl portion is of 3 to 6; b) R is hydrogen, fluoro, chloro, bromo, CF^ orC^-C4 alkyl; c) R' is hydrogen, fluoro, chloro, bromo, C^-C^ alkyl, C^-C^ alkoxy, alkylthio of 1 to 4 carbon atoms, CN, wherein Y° and Y are as above defined; d) R‘ is hydrogen. The more preferred among the above-mentioned preferred compounds of the formula I have one or more and preferably all of the following features: a ) ρ is hydrogen, fluoro. Cl, Br, CF^ or C1~C2 alkyl; and b) R' is hydrogen, fluoro, Cl, CN, alkyl or C^-C^ alkoxy; or d) R is hydrogen and R' is located at the para-position of Ring A, more preferably with Y° and Y being hydrogen.

The following examples further illustrate the present invention. All temperatures are in centigrade. - 19 EXAMPLE 1 α-cyclohexylmethyl-q- (p-methylphenyl)-1H-1,2,4-triazole-lethanol A portion of 61.4% sodium hydride is washed three times with petroleum ether and then dimethylformamide is added while maintaining stirring. To the resulting suspension is added slowly with stirring triazole in dimethylformamide followed by stirring at 20° until bubbling ceases. To the resulting mixture is then added 2-(cyclohexylmethyl)-2(4-methylphenyl)-oxirane followed by heating with stirring at 90° for 6 hours. The resulting reaction mixture is then poured onto water, extracted with ethyl acetate, dried and chromatographed over silica gel while eluding with hexane/chloroform (50:50) to obtain a yellow oil which crystallizes on standing to a solid which on recrystal15 lization from ethanol yields a-cyclohexylmethyl-α- (p-methy 1 phenyl)-lH-l,2,4-triazole-l-ethanol, m.p. 79-81°.

EXAMPLE 2 Following the procedure of Example 1 the following additional compound of the invention is obtained: a-cyclopentylmethyl-a-p-methylphenyl-lH-1,2,4-triazole-lethanol, m.p. 74-76°.

Claims (22)

WHAT IS CLAIMED IS:

1. A compound of the formula R* wherein R° is eycloalkylalkyl of 4 to 11 carbon atoms in which the cycloalkyl portion is of 3 to 5 8 carbon atoms and the alkyl portion of 1 to 3 carbon atoms, said eycloalkylalkyl group being optionally substituted by one or two alkyl groups of 1 to 3 carbon atoms, 10 R is hydrogen, halogen having an atomic number of from 9 to 35, alkyl of 1 to 4 carbon atoms, mono-, di- or tri-haloalkyl of 1 to 4 carbon atoms in which the halo is independently an halogen having an atomic number of from 9 to 35, alkoxy of 1 to 4 carbon atoms, alkylthio - 21 of 1 to ί carbon atoms, or nitro, and R' is hydrogen, halogen having an atomic number of from 9 to 53, alkyl of 1 to 4 carbon atoms, mono-, di- or tri-haio5 alkyl of 1’ to 4 carbon atoms in vzhich the halo is independently an halogen having an atomic number of from 9 to 35, alkoxy of 1 to 4 carbon atoms, mono-, di or tri-haloalkoxy of 1 to 4 carbon 10 atoms in vzhich the halo is independently an halogen having an atomic number of from 9 to 35, alkylthio of 1 to 4 carbon atoms, nitro, -CN, -COOR, R is hydrogen, alkyl of 1 to 4 carbon atoms, 15 R‘ is hydrogen, an halogen having an atomic number of from 9 to 17 or alkyl of 1 or

2. Carbon atoms, Z is oxygen or sulfur, or R and R' together represent alkylenedioxy of 1 or 20 2 carbon atoms substituted onto adjacent carbon etoms of the phenyl Ring A, and S1004 - 22 Y° and Υ are independently hydrogen, halogen having an atomic number of from 9 to 35, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to . 4 carbon atoms. 5 2. A compound of Claim 1 in which R is hydrogen, halogen having an atomic number of, from 9 to 35, CF^ or C^-C^alkyl, R' is hydrogen, halogen having an atomic number of fro- 9 to 35, C^-C^alkyl, C^-C^alkoxy, C^-C^alkylthio, CN, 1θ in which Y° and Y are as defined in Claim 1, and R' is hydrogen.

3. A compound of Claim 2 in which R is hydrogen, F, Cl, Br, CF 3 or C^-C^lkyl and R' is hydrogen, fluoro, chloro, CN, C^-C 2 alkyl or C^-C 2 alkoxy. 15

4. A compound of Claim 2 in which R is'hydrogen and located at the para-position of Ring A, and in which Y° and Y are as defined in Claim 1. - 23 5. A compound of Claim 4 in which Y° and Y are each hydrogen. 6. A compound according to any one of Claims 1 to 5 in which R° is cycloalkylmethyl in which the cycloalkyl

5. Portion is of 3 to

6. Carbon atoms. ,

7. The compound of Claim 6 which is α-cyclohexyImethyΙα- (p-methylphenyl)-1H-1,2,4-triazole-l-ethanol.

8. The compound of Claim 6 which is α-cyelopentyImethyΙα- (p-methylphenyl)-1Η-1,2,4-triazole-l-ethanol.

9. 10 9. A compound according to any one of Claims 1 to 8 in free form. 10. A compound according to any one of Claims 1 to 8 in salt form or metal complex form.

10. 11. The method of combatting phytopathogenic fungus 15 in plants, seeds or soil comprising treating said plants, seeds or soil in a manner conventional in the use of fungicidal agents with a compound claimed in any one of Claims 1 to 8 in free form or in an agriculturally acceptable salt or metal complex form. 20

11. 12. The method of combatting phytopathogenic fungus in plants or soil comprising applying to said plants or soil 0.005 to 2 kg per hectare of a compound claimed in any one of Claims 1 to 10. - 24

12. 13 . The method of Claim 12 , wherein the application rate is from 0.01 to 1 kg per hectare of a compound claimed in any one of Claims 1 to 10.

13. 14. The method of combatting phytopathogenic fungus 5 in seeds comprising applying to the seeds 0.05 to 0.5 g per kg seed of a compound claimed in any one of Claims 1 to 10.

14. 15. The method of Claims 14, wherein the application rate is from 0.1 to 0.3 g per kg seed of a compound 10 claimed in any one of Claims 1 to 10.

15. 16. A fungicidal composition comprising a compound claimed in any one of Claims 1 to 8 in free form or in agriculturally acceptable salt or metal complex form in association with a fungicide carrier or diluent. 15

16. 17. The composition of Claim 16, comprising from 0.0005 to 90% by weight of a conpound claimed in any one of Claims 1 to 8 in free form or in agriculturally acceptable salt or metal complex form.

17. 18. An application form of the composition of Claim 20 17, comprising from 0.0005 to 10% by weight of a compound claimed in any one of Claims 1 to 8 in free form or in agriculturally acceptable salt or metal complex form. - 25

18. 19. A concentrate form of the composition of Claim 1.7, comprising from 2 to 90% by weight of a compound claimed in any one of Claims 1 to 8 in free form or in agriculturally acceptable salt or metal 5 complex form.

19. 20. A process for the production of compounds of formula I, stated in Claim 1, which comprises a) reacting a compound of the formula II: R 1 wherein R®, R, R' and R* are as defined in claim 1 with a comDound of formula III /=H Ϊ-Ν ted III wherein X is an alkali metal in an inert organic solvent, b) obtaining a compound of formula Ia, R•ROOC OH c - CH 2 R° /=-N V la wherein R° and R are as defined in Claim 1 - 26 by oxidation of formula lb, the CH 3 group of a compound of c) wherein obtaining R“ and R are as defined in Claim 1, or a compound of formula Ic, Ic 5 wherein R and R° are as defined in Claim 1 and Alk is C 3 _ 4 alkyl, by esterification of a compound of formula Ia with an alcohol of formula IV Alk-OH IV wherein Alk is as defined in this Claim, or a reactive functional derivative thereof. 10

20.

21.A process according to Claim 20, substantially as hereinbefore described with reference to any one of the Examples.

22. A compound of formula I, stated in Claim 1, whenever obtained by a process according to Claim 20 15 or 21.