AU624149B2

AU624149B2 - Process for the preparation of substituted anilides

Info

Publication number: AU624149B2
Application number: AU36637/89A
Authority: AU
Inventors: Hans-Peter Buser; Wolfgang Eckhardt; Benoit Pugin; Felix Spindler; Marius Sutter
Original assignee: Ciba Geigy AG
Current assignee: Novartis AG
Priority date: 1988-06-22
Filing date: 1989-06-20
Publication date: 1992-06-04
Anticipated expiration: 2009-06-20
Also published as: AU3663789A; IL90685A0; DD284009A5; HUT50147A; HU206699B; EP0348351A1; ZA894704B; KR900000353A; FI892984A0; FI892984A; JPH0245480A

Description

S F Ref: 98541 FORM COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952 COMPLETE SPECIFICATI

(ORIGINAL)

FOR OFFICE USE: Class Int Class Complete Specification Lodged: Accepted: Published: t Priority: Related Art: Name and Address of Applicant: Ciba-Geigy AG Klybeckstrasse 141 4002 Basle

SWITZERLAND

Address for Service: Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia S Complete Specification for the invention entitled: Process for the Preparation of Substituted Anilides The following statement is a full description of this invention, including the best method of performing it known to me/us 5845/6

F_

Abstract A multi-step process for the preparation of chio rophenyl) I -amino- te trahyd ro- 2-f uranone s of formula I 0\\ 6i 0)~ 00 o o 0 0 00 00 0 0000 o 00 00 0 0000 04 o~ 00 0 o 0 0 00 0~ 0 0 00 0 0 0 00 0 00 00 0 0000 0000 0 0000 00 0 0 0 0 00 wherein each of R, and Rz, independently of the other, is methyl or ethyl and R3 is methyl, chioromethyl, methoxymethyl or cyclopropyl, is described.

This process comprises oxidising am a-phenylamimo- r-bu tyro lac tone of formula V to give a 3-(phenylamino)-2,5-dihydro-2-furanone of formu~la IV /R1N- 0i (v) \R2\

IV)

acylating the lat er with a carboxylic acid halide or carboxylic acid anhydride off formula VI R3-9_ /R1

~-R

~R Z R

(VI)

IA-

wherein X is chlorine, bromine or the radical R 3 COO-, to give a 3-EN- (acyl)-N-(phenyl) I-amino-2,5-dihydro-2-furanone of formula III, hydrogenating the resulting product with hydrogen in the presence of an enantioselectively active catalyst to give a 3-IIN-(acyl)-N- (phenyl) ]-amino-tetrahydro-2-furanone of formula II \2 gR3 converting the hydrogenated product by chlorination into the (aR,1'R; aS,1 diastereoisomeric mixture of the 3-[N-(acyl)-N-(3-chlorophenyl)1gmino-tetzrahydro-2-furanones of formula I, and isolating the (aS,1'R) 0 enantiomer therefrom by crystallisation from a solvent.

P-00 The (aS,1'R) enantiomer exhibits an increased microbicidal activity o compared with the mixture of isomers.

00 00 0 0 The intermediate of formula 00030 0~s 0.0 0 0 a00

N

0 0 ~CH 3 is also microbicidally active.

5-17100/+ Process for the preparation of substituted anilides The present invention relates to a process for the preparation of inicrobicidally active (aS,1 'R)-3-[N-(acyl)-N-(3-chlorophenyl) ]-aminotetrahydro-2-furanones and for the preparation of (aR,1'R; aS,1'R)-3- [N-(acyl)--N-(3-chlorophenyl) ]-amino-tetrahydro-2-furanones, to novel intermediates some of which are microbicidally active, to microbicidal comp~ositions that contain these active ingredients, and to the use of 0 those compositions as microbicides in plant protection.

0 co 00 00 00 0 0 Some of the substituted anilides that are known as microbicides contain 0 00 0 0 centres of asymmetry and can accordingly occur as stereoisomers.

a 0 00 0 00.0 o (nethoxyacetyl)-N-(3-chloro--2, 6-dimethylphenyl) ]-amino-tetrahydro- 0 0 2-furanone of formula Ia 0000 000Cl\ CH 3

I

00 0 000 /0 (Ia) CCH0OCH3 00 00u whichi is known as a xnicrobicide from DE-OS 2,804,299 (~GB-1,577,702) has 000 as 4itructura1 feature the centre of asymmetry marked ~.As a raremate, it 0 c,-n be regolved into optical antipodes in conventional manner, the different configurati-ons dt.ffering in the strength of their miqrobicidal ao~tivity.

Beyond that, DE-OS 2,804,299 does ftot reveal, within the broad chemical scope disclosed therein, any details of futther possibilities of isomnerism outside the furanone ring.

'I *f -2- However, in the compound of formula I conventionally obtainable as a racemate there is not just a single pair of enantiomers by virtue of the asymmetric substitution at the indicated *C-atom, but a mixture of 4 isomers, that is to say two diastereoisomeric pairs of enantiomers.

The reason for this is that, in a tion to having the centre of asymmetry mentioned, the molecule also has a rotational isomerism (atropisomerism) contingent on the chiral axis and caused by the asymmetric chlorine substitution of the 2,6-dimethylphenyl ring in which rotation is hindered. The 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]amino-tetrahydro-2-furanone prepared according to DE-OS 2,804,299 is a diastereoisomeric mixture that can be separated by adsorption chromato- 'ri' graphy or crystallisation and that consists of two diastereoisomeric I t pairs of enantiomers which melt at 140' and 115', respectively, and which each form approximately 50 of the mixture, These two diastereoisomeric S pairs of enantiomers can be resolved into optical antipodes in conventional manner. The (aS,1'S) and (aR,1'R) enantiomrs of 3-[N-(methoxy- S acetyl)-N-(3-thloro-2, 6-dimethylphenyl) )-amino- tel rahydro-2-furanone can be isolated from the diastereoisomeric pair of evantiomers that melts at o 14000, and the (aR,1'S) and (aS,1'R) enantiomers can be isolated from the 009 Q diastereoisomeric pair of enantiomers that melts at 115 0 C, for example by chromatography on an optically active phase.

o 0 So 4o The (aS,1'R) enantiomer of 3-[N-(methoxyacetyl)-N-(3-hloto-2,6-dimethylphenyl)]-amino-tetrathydro-2-furanone has a very greatly enhanced microbicidal activity accompanied by an unexpectedly long duration of 0, 0 action compared with the diastereoisomeric mixture of formula Ia.

The diastereoisomeric mixture (aR,1'R; aS,1'R)-3-[N-(methoxyacetyl)-N- (3-chloro-2,6-dimethylphenyl)]-amino-tetrahydro-2-furanome obtainable by chlorination of (1'R)-3-([N-(methoxyacetyl)-N-(2,6-dimethylphenyl) amino-tetrahydro-2-furanone of formula Ila Throughout, the asymmetric C-atom which is in the 3-position of the lactone ring and which is adjacent to the N is referred to as (1'R) or when indicating the configuration.

3-

CH

3 H\ 1

I

CH2 CH3 CH3 0 (IIa), 9 9 0 09 o a 0000 7 0 o 00 9 ao 0 0 90 0 0 0 00 0 also exhibits substantially increased microbicidal activity compared wi'h the diastereoisomeric mixture obtainable according to DE-OS 2,804,299, the extent of the increase in activity being smaller than that in the case of the (aS,I'R) enantiomer.

No processes are known from the literature, however, for the preparation of the (aS,1'R) enantiomer or the (aR,1'R; aS,1'R) diastereoisomeric mixture of 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-aminotetrahydro-2-furanone or for the preparation of (1'R)-3-[N-(methoxyacetyl) 2,6-dimethylphenyl)]-amino-tetrahydro-2-furanone. The object of the present invention is therefore to provide a superior process for the preparation of these compounds.

A further object of the present invention is to provide novel microbicidally active substances.

i It has been found that the (aS,1'R; aR,I'R) isomeric mixture of 3-[N- S" (methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl) ]-amino-tetrahydro-2furanone can be prepared by a multi-step enantioselective synthesis, and that it can be separated into the two enantiomers (aS,I'R) and (aR,'R) "0* n by crystallisation.

ao9 00 0 6 0 0 0 The enantioselectivity is contingent upon an asymmetric hydrogenation of a cyclic enamide intermediate that proceeds in the presence of enantioselectively active catalysts. Enantioselectivity is defined as the preferential formation of one of the two possible enantiomerit reaction products, in this case the reaction products of the hydrogenation.

By the selection of suitahb'.e catalysts the enantiomer that is more valuable from the point of view of the invention is preferentially produced.

~I

I

A

-4 The present invention accordingly relates to a process for the preparation of (aS,1 'R)-3-[N-(acyl)-N-(3-chlorophenyl) ]-amino--tetrahydro-2furanones of formula I Cl /Rl \2 wherein each of R, and R 2 independently of the other, is methyl or ethyl and R 3 is methyl, chloromethyl, methoxymethyl or cyclopropyl, which process comprises a) oxidising an ca-phenylamino-y-butyrolactone of formula V 4' 4 4 4 444 44 44 4. 4 0 4 4 44 4 4 4 444# 4 40 44 4 4044 44 44 44 4 4 4 4 4 40 4 4 00 4 0 00 4 04 04 4 40044 4440 0 4 0040 44 0 0 00 4 04

(V)

4 wherein R, and R 2 are as defined above, to give dihydro-2-furanone of formula IV \2 a 3-(phenylamino)-2, (IV) wherein RI and R 2 are as defined above, b) acylating the latter with a carboxylic acid halide or carboxylic acid anhydride of formula VI R3-9_

(VI),

wherein R 3 is as defined for formula I and X is chlorin~e, bromine or the radical R3COO-, to give a 3-4N-(acyl)-N--(phenyl)]-amino-2,5-dihydro-2furanone of formula III 0i wherein R 1

R

2 and R 3 are as defined above, c) 'hydrogenating the resulting product with hydrogen in the presence of an enantioselectively active catalyst to give a 3-IiN-(acyl)-N- (phenyl) ]-amino-tetrahydro--2-furanone of formula IT 0 boo4

(IT),

04 04" a4 0 4 040 d) converting the hydrogenated product by chlorination into the (aR,,l1'R; 44 'n 044 aS,l'R) diastereoisomeric mixture of 3-IN-(acyl)-N-(3-chlorophenyl)]amino-tetrahydro-2--furanones of formula I, 0 e) and isolating the (aS, 1'R) enantiomer therefrom by crystallisation from a solvent.

S The invention relates not only to the overall process but also to the individual process steps thereof, it being possible, if desired, to 00. isolate the intermediates of formulae II, III, TV and V; the invention also relates to the novel intermediates of formulae III and IV. The 400 Sintermediate of formula Ilia cu gH200lb, has microbicidal properties and is therefore also to be given prominence as an active substance.

6 -6- The process is preferably carried out with those compounds of formulae II to VI in which R 1 and Rz are methyl, R 3 is methoxymethyl and X is chlorine. These result in the compound of formula Ia.

A preferred embodiment of the oxidation in accordance with the invention of compounds of formula V to give compounds of formula IV comprises carrying out the reaction with manganese dioxide as oxidising agent in a solvent at 40-140 0 C. Oxidation in toluene at 85-112 0 C, or in diethyl ether, is especially preferred in this case.

The embodiment of the oxidation in which a cerium(IV) compound is used as oxidising agent is also preferred.

o" Another preferred embodiment of the oxidation of compounds of formula V is carried out with a peroxide or a peracid as oxidising agent in a o solvent at from -10' to +40'C under atmospheric pressure and results in the corresponding [N-(hydroxy)-N-(2, 6-dialkylphenyl)]- amino-tetrahydroo o, 2-furanone derivative. The latter is converted into the compound of formula IV by removing the elements of water. Oxidation with m-chloroperbenzoic acid as oxidising agent in tetrahydrofuran at 0-10 0 C is o, especially preferred in this case. The removal of the elements of water can be etfected by the addition of a dehydrating agent, such as, for example, basic aluminium oxide, 4 0 0 When carrying out the oxidation with m-chloroperbenzoic acid on a relatively large scale, tetrahydrofuran can advantageously be replaced by S o other suitable solvents. Such solvents are halogenated hydrocarbons, S especially halogenated aliphatic hydrocarbons, for example dichloromethane.

The acylation of a compound of formula IVa with an excess of 50-500 of the theoretical amount of the compound of formula Via to give the compound of formula lila, in the presence or absence of a solvent, such as, e.g. toluene, with the hydrogen chloride produced as by-product being driven off by boiling under reduced pressure at 4 0-60 0 C, is a preferred embodiment of the acylation step of the process according to the invention.

-7- A preferred embodiment of the enantioselective hiydrogenation in accordance with the invention of a compound of forv'ula lIla to give the (1'R) enantiomer of the compound of formula Ha is !:tarried out in the presence of catalytic Amounts of rhodium compounds of the formula VII or VI~a [XRhYZ] (VII) or [XRhY]OAG (VI~a) wherein X represents two olefin ligands or oie diene ligand, Y is a chiral diphosphine in which the secondary phosphine groups are linked by 2 to 4 carbon atoms and that forms, together with the Rh atom, a 6 -or 7-membered ring, or Y is a chiral diphosphinite in which the phosphinite groups are linked by 2 carbon atoms and that forms, together witji the Rh atom, a 7-membered ring, Z is chloride, bromide or iodide, and A is the anio~n of an ox.ygen or complex acid, in An alcohol as solvent, under 0.1-150 bar at from, -20 to +70'C. Spocial preference is given in this 00 case to ca~rying out the hydrogenation in the presence of 0,002-10 mol. ain each case o~f bis-norbornadienyl-rhodium(I) tetrafJluoroborate and piooty)- -ioty~ 3-dioNolane, based on the compound of formula Iila, in methanol under 1-70 bar at 0-500 c.

0 A likewise preferred embodiment of this en~ntiosqlective hydrogenation is carried out in the presence of catalytic amounts of a Ru (R)-2,2'-bis- (diarylphosphiio)-1,1'-binaphthyl salt of formula Villa or a Ru 2, 2'-bis (diarylpho sphino) 1 '-binaph thy! salt of formula Vitb 2 Z 2 Z IRu RU (Villa)(Vl) wherein R4 is a phenyli radical that is, unsubgtituted or mooubtituted by Cj-Ozkalkyl or by methoxy, or is a 1- or 2-naphthyl radcial, and 4- is aithat an anion of the formula 1R$CO0-, wherein Rs is 01-C$alkyl or CV~, or is the trif3uoromothanesulfonato anion, in an Alcohol as solvent, -8under 0.1-150 bar at -20 to +70 0 c. Special preference is given in this case to carrying out the reaction in the presence of 0.002-10 mol. of Ru or (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl diacetate, based on the compound of formula Ila, in methanol under 1-70 bar at from 0 to 500.

The chlc~inating agent used in the case of the compounds of formula It to give the compounds of formula I is preferably elemental chlorine, When isolating the (aS,1'R) enantiomer of formula Ia, methyl ethyl ketone is preferred as the solvent, The present invention also embraces a process for the preparation of the S (aR,1'R; aS,1RP) diastereoisomeric mixture in a ratio of 1:1 of formula 1, which process differs from the procedure just described only 0 ,0 inasmuc~h as the diastereoisoMeric mix~ture obtained after chlorination 4 of the compound of formula It is isol~ated in that form instead of the aS, I'R ennt OMer being separated, Preference is given in this case to the preparation of the s,11RQ diasteruoisomerio Mixture of 3-(N- (tl thamino tl-tNetrahhyro-, 6di~thyp.2yl f'jranone Of formula Ia.

The present invention also relates to a process for the PreP4,ration of 0 the (aS,1I'R; aRt I'P) diastereoisomorio mixture of formula Ia by heating the (aRX1R) enantiomer of the same compound at from 160 to 180 0 0 for from 1 to 3 hours. This process is preferably carried out in accordance with the invention in the presence of tetrabotylammonium bromide.

Teoxidation in, acc. rdance with the invention of the known compounds of formula V to give the compounds of formula TV, which may also be regarded as the dohydrogonation of an amine, is also novel* the resulting compounds of formula IV also being novel, NJor has the acoylation of those compounds in accordance with the inventiont with the darboxylic acid derivatives of formula VI to give the novel enamtides of formula III boon described hitherto, The: preferred earboxylio. acid derivative is methoxyaaety. chloride. The ACy1lition may also be carried out, ae. is customaryt in the presence of equivalent aM6onts Of bases, such asf for ex~amples 9tert.-amines. The yields that are to be obt~i I~n so doing are, however, moderate. The presence of catalytic amounts of carboxylic acid dialkylamides, such as, for example, dime thylf ormamide, instead of tert.-amines also increases the yield only negligibly. The best results can be achieved according to the invention in the absence of bases or amides and with excess acid chloride, the hydrogen, chloride produced as by-product being driven off from the reaction mixture at di temperature at which the latter boils (optionally under reduced pressure).

The intermediates of formula IV are novel and the present inventi,, relates to them also, The likewise novel compounds of formula III have stirpisingly proved to be fungicides and the present invention relates to them also. Of these compounds, 5-(N-(methoxyacetyl)-N-(2,6-dimethylaaaphenyl)]-amino-2,5-dihydro-2-furanone of formula Mia is preferred, a The starting materials of formulae V and VI in the process of the a0oinvention are known or can be prepared analogously to known methods, 0 At the centre of the process of the invention, lies the enantioselective preparation of the compounds of the 3-(N-(aqyl)-N-(phenyl) I-aminoa tetrahydrp-2-furanoneg of formula II starting from the corresponding a 0 -phenyl-amino--y-botyrolactones of formula V.

0 00I 0 rot this, in accordance with the invention said laqctone ig Cirst wctdised kor dehydrogenatod) to the corresponding 3-(phenylamoino)-2,$-,,L-.*.'Iro-tc-2furanono of formuila IV, the centre of asymmetry In the 3-position of the a afuran ring being removed. After aq~lation of tht. qnninide of formula IV to Sgive the onamide of formula III, the letter is hydrogenated in accordance lith the invention to give the (1'R)-3-tN-(acyl)-N-(phenyl)1-anin6-t~tta hydro-2-furanone of formula 11. As a~ result of this asymmetric hydrogenationt a Centre of asymmetry i$ 4ain prodoced in the 3-position of the furan ring, with the formation of the undesired its enantiomor being largely suppressed in favour of the desired 1'R enantiomer by suitablo measuresf Asymmetric hydrogenation in the prosence of rhodium catalysts, as are also defined under formulae VII and VIla, or in the presence of ruthenium compounds, as defined under formulae VIII and VIlla, are known from the 2 literature The a.*ymmetric hydrogenation in accordance with the invention of the C=C double bond of the N-phenyl-enamides of formula III is novel.

This hydrogenation variant is preferably carried out in the presenco of Q,002-10 mol. in each case of a rhodium catalyst of formula VII or VIla 9 i or a ruthenium catalyst of formula VIII or VIIla, based on 'lie compound of formula II I used.

SThe reaction is preferably carried out in solvents, such as alcohols, for o example methyl, ethyl, propyl or butvl alcohol; hydrocarbons, for examplo hexane, toluene, cyclohe,~ane, methylcycloheae;ebes for excample 0 diethyl ether, tetrahydrofuran, dioxane; or esters, for example othyl oGO acet te, The catalysts of formulae VII and Villa are known Zfrom the literature 0(see Reference Literature). Bi8-norbornadienyl-rhodium(I) tetrafltuoroo borate ana O4R, 5R) 5-bis- (diphenylphosphinome '1yl) -2 2-dimp thyl 1,3-dioxolane are available commercially.

The catalysts of formulae VIII and Villa are also known from the literature (TE. Okta, Ho Takaya, X.t Kitamura, K. Nagai, R. Noyori, J. Org. Chem.

1987, 52, 3174-3176; T. Okta, H. Takaya, R. Noyori, Inorg., Chem, 1988, o 7, 566-569).

2 Reference literature: K. Koenig, Thq applicability of asymmetric homogeneous catalytic hydrogenation in Asymmetriq Synthesisi Vol.. 5, S. Morrison Academic Press Inc., 1985, tpp, 71 ff.

Halporn, Asymmetr~ic catalytic hydrogenation, ibid, p. 41 ff, H.B. Ragan, Chiral Ligands for asymmetric catalysis, ibid, pp. 13-23*

I

11 The asymmetric hydrogenation in accordance with the invention is carried out under a hydrogen atmosphere, preferably under an excess pressure of from 0.1 to 150 bar. A pressure range of from 1 to 70 bar is especially preferred. A temperature range of from -20 to +70 0 C, especially one of from 0 to 50 0 C, is preferred as the reaction temperature.

From the 3-[N-(acyl)-N-(phenyl)]-amino-tetrahydro-2-furanones it is possible to obtain by chlorination the (aR,1'R; aS,1'R) diastereoisomeric mixtures of the 3-[N-(acyl)-N-(3-chlorophenyl)]-amino-tetrahydro-2furanones of formula I which either can be used themselves as microbicides or can be separated into the (aR,l'R) and (aS,1'R) enantiomers.

The process of the invention provides access to highly active stereo- S isomers and mixtures thereof, especially to the (aR,1'R; aS,1'R) di- S* o astereoisomeric mixture and to the (aS,1'R) enantiomer of 3-[N-(acyl)- 'oe 0 N-(3-chloro-2,6-dimethylphenyl) -amino-tetrahydro-2-furanone, that is of 4 o, interest from an economic point of view with regard to production on an o0 industrial scale.

4 a The less active (aR,1'R) enantiomer which is obtained as by-product of do°. the process of the invention can, according to the invention, be thermally re-isomerised to give the valuable (aR,1'R; aS,1'R) diastereoisomeric mixt're of 3-[N-(acyl)-N-(3-chlorophenyl)]-amino-tetrahydro-2a 0 furanone and used again as such in the manner described (recycling).

Owing to the lack of enantioselective methods of preparation, up to now o" it has been possible to prepare the diastereoisomeric mixtures and B, enantiomers mentioned herein, which are of great value owing to their microbicidal activity, only with the aid of expensive methods that are unsuitable for industrial application.

Also significant is the discovery, made within the scope of the present invention, of the surprising microbicidal activity of the compounds of the 3-(phenylamino)-2,5-dihydro-2-furanones of formula IV.

The process of the invention will be explained in detail by the following Examples.

4 4 044 44 4~ 14 4' 4 4 48 4 4444 4 44 4 44 44 40 4 a 4 tO 424 4 04 44 02 4 0 42 4' 0 04' 42 04 4 o ~O '2 00 '2 ~0 0 to 4' 44 4 0 04 0 44' 12 Preparation Examples Example P1: Preparation of 3-[N-(2,6-dimethylphenyl) hydro-2-furanone using man,,n-ese dioxide as oxidising agent (cf. Journal of Organic Chemistry, 29, 1540 (1964)].

48.6 g of manganese(II) sulfate mQnohydrate, dissolved in 84 ml of water, and 65 ml of 40 sodium hydroxide solution are simultaneously added dropwise, over a period of 45 minutes, to a solution, at 75'C, of 53 g of potassium permoanganate in 330 g of wa'ter, and the mixture is them stirred for 1 'hour at 80'0. The precipitate is filtered off, washed neutral with hot water and dried in vacuc at 125'C. The 48,3 g of manganqse dioxide obtained are suspended in 300 ml of toluene and boiled for 3 hours using a water separator. Then, 13,6 g of 2-(2',6'-dimethylphenylamino-y-h-utyrolactone are added and the whole is boiled overnight using a water separator. The solution is filtered And concentrated by evaporation.

Chromatography on silica gel using ether/hexane 1:1 as eluent yields 5,7 g (42 To of the theoretical amount) of 3-[N-(2,6-dimethylphenyl)1 amino- 2, 5-dihyd rQ-2 -f uranone in the form of brown crystals R-p, after recrystallisation from ether/hexane: $4-85 0

C.

Example P2: Prevarvtior. of 3-[N-(2,6-dimethylphenyl)-ami-o? S-dihvdro 2-furanone using cerium(IV) ammonium nitrajte as oxId Isng agent 433 mg (2.1 mmol) of 2-(2,5-dime thylpenylanino) -7-bu tyro lac tone are added to a suspension of 3,47 g (6.3 momol) of cerium(IV) ammonium i~itrate in ?ZK ml of methylene chloride. After stirring for 18 hours at room temperature, the orange reaction mixture is filtered and the filtrate is concentrated by evaporation. Chromatography cf tho~ residue on silica gel using hexane/ethy. acetate 2:1 as eloant yields 190 mg (44 of the theoretical amount) of 3-IN-(2,6-dimethylphenyl) ]-amino-2,5-dihydro-2 foranone in the form of a yellow-brown crystalline product which was recrystallised from hexane/ethyl acetate 3i:1 (mip. 8 5 8 6

QC).

i e 13 Example P3a:. Preparation of 3-[N-(2,6-dimethylphenyl) hydro-2-furanone using m-chloroperbenzoic acid as oxidising agent A solution of 60.9 g (0.35 mol) of m-chloropetoenzoic acid in 200 ml of absol,-te tetrahydrofuran is added within a period of from 30 to minutes at 0 0 C to a solution of 61.5 g (0.3 mol) of me thylphenylamino) -7-bu tyro lac tone in 200 ml of absoluce tetrahydrofuran.

The reaction mixture is stirred for 80 minutes at and filtered through 1 kg of basic aluminium oxide (ICN; Akt. I) while cooling the receiving vessel with ice. The aluminium oxide is elvted with tetrahydrofuran; the first 6Q0 ml of eluate contain the majority of the 3-[N-(2,6-dimethylphenyl) 1-amino--2,5-dihydro-2.-furanone formed: 35.15 g in the form of white crystals (57.6 of the theoretical amount), Mip.

after recrystallisation from hexane: 85-860C.

Ct 4*1 t~ t~ 'Example P3b: Preparation of 3- 6-dime thvlphenyl)]-amino hydro-2-furanone using m-chloroperbenzoic acid as oxidising agent 0 A sol~ution of 60.9 g (0.35 mol) of m-ohlo rope rbonz oic acid in 200 ml of dichloromethane is added within a period of from 30 to 60 minutes at 0 0

C

to a solution of 61.5 g (0.3 mol) of 2-(2',6'-dimethylphenla

I-

040 0 r-butyrolactone in 200 ml of dicliloromethaneo The reaction mixture is 0, stirred for 80 minutes at OCc. After filtration' through a small amount of basic aluminium oxide (ICN; Akt. the solvent is evaporated in vacuo -3 0OA and the residue is dissolved in 400 ml of tetrahydrofuran. The solution is filtered through 1 kg of basic aluminium oxide while cooling the receiving vessel with ice and is worked up analogously to E>~xmple 3a.

R, ~esult: 35.15 g of product in the form of white crystals (57.L of the 0 theoretical amount). H.po after recrystallisation from hexane: 5 8 6 a 0

C

Example P4: Pireparation of 3-[N-.(methoxyacetyl)-N.-(2,6-dimnethylphenyl) 1 ,amino-2, 5-dihydro-2-furanone 10.2 g (50.2 mmol) of 3-'CN-(2,6-dimethylphenyl) ]-amino-.2,5-dihydro-2furanone, 40 ml (439 mmol) of methoxyacetyl chloride and 40 ml of toluene are mixed and boiled under reflux at 50-70'C and 100-150 mbar for 48 hours. The reaction solution is then concentrated by evaporation, and the residue is dissolved. in a mixture of hexame/ethyI acetate and t I 14 chromatographed on silica gel. Elution is carried out with a mixture of hexane/ethyl acetate The 3-[N-(methoxyacetyl)-g-(2,6-dimethylphenyl)]-amino-2,5-dihydro-2-furanone obtained after evaporation of the solvent and recrystallisation of the residue twice fron a mixture of hexane/ethyl acetate melts at 106-107 0

C.

Example P5: Preparation of 3-IN-(methoxyacetyl)-N-(2,6-dimethylphenyl) iamino-tetrahydro-2-furanone in the presence of bis-norbornadienyl-rodium(I) tetrafluoroborate and (4R,5R)-(c)-4,5-bis- (diphenylphosphinonethyl)-2,2-dimethyl-1 3-dioxolane 0.9 g (4 mmol) of 3-IN-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-amino- 2,5-dihydro-2-furanone dissolved in 10 ml of methanol are introduced into 0D a 60 ml steel autoclave, and then 29 mg (0.08 mmol) of bis-norbornadi- 0 40 0 enyl-rhodium(I) tetrafluoroborate and 44 mg (0.08 mmol) of 4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-1 ,3-dioxolane, dissolved in 0 00 S'o0 10 ml of methanol, are Prlded. The catalytic hydrogenation with hydrogen 000 is carried out at from 20 to 22' 0 with an initial pressure of 33 bar o hydrogen, until absorption ceases (about 1 hour).

The residue obtained after filtration and concentration by evaporation is 0 I dissolved in methylene chloride/methanol 98:2 and chromatographed on 0 silica gel. The product mixture obtainable after evaporating the solvent is obtained in quantitative yield, 90 thereof consisting of the (1'R) 0 0~OO enantiomer of 3 N-(mthoxyacetyl)-N-(2,6-dimethylpenyl) I-amino-tetrahydro-2-furanone and 10 consisting of its antipode.

uow The pure enantiomer can be obtained in pure form in 75 yield 0 after recrystallisation from hexane/methyl ethyl ketone 1:1.

Example P6: Preparation of 3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]amino-tetrahydro-2-furanone in the presence of Ru or (S)-2,2-bis(diphenylphosphino)-1 ,l1'-binaphthy1 diacetate 0-.45 g (2 nmol) of 3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-amino- 2,5-dihydro-2-.furanone dissolved in 10 ml of methanol is introduced into d 60 ml steel autoclave, and then 33.6 mg (0.04 mmol) of Ru or (S)-2,2-bis(diphenylphosphino)-1 ,1'-binaphthy diacetate are added. The catalytic hydrogenatcri with hydrogen is carried out at from 20 to 22'C, under an initial pressure of 30 bar hydrogen, until absorption ceases (about 1 hour).

The residue obtained after filtration and concentration by evaporation is dissolved in methylene chloride /methanol 98:2 and chromatographed on silica gel. The product mixture obtainable after evaporating the solvent is obtained in quantitative yield, 83 thereof consisting of the (1'R) enantiomer of 3-IrIN- (me thoxyace tyl) 6-dime thylphenyl) I-amino- te trahydro-.2-furanone and 17 consisting of its antipode.

The pure enantiomer can be obtained in pure form in 65.7 yield after recrystallisation.

44 0 4 Exam-le P7: Preparation of the (aR,1'R) and (aS,1'7, gixture of 3-[N- (me th oxya c e tl) 3-chlo ro -2 6 -dime thylphenyl) amino -te traa a hydro-2-furanone in a ratio of approximately 1:1 0.222 g of (1'R,)-3-[N-(methoxyacetyl)-N-(2,6-d;Lmethylphenyl)I-aminQtetrahydro-2-furanone is dissolved in 30 ml of formi±c acid. At room temperature, 0.06 g of chlorine is Introduced into the solution in the 0 0 '1 00 presence of 5 mg of iron(III) chloride. The solution is stirred at room 4temperatu~re for approximately 1 hour and the solvent is evaporated under reduced pressure. The residue is dissolved in ethyl acetate, and the solution Is extracted with water, dried over sodium sulfate) filtered and concentrated by evaporation. Having been dried, the mixture elts at 79-82'C; each of the two isomeric title products forms approximately 50 Sof the mixture.

Example P8: Preparation of (aSI N-(methoxyacetyl)-N-(3-cioro-- 2,,6-'dime thylphenyl) I -amino- te trahydro-2 -f uraione from the (aR,1'R),and (aS,I'R) mixture of 3-IIN-(methoxyacetyl)--N-(3chloro-2 ,6-.dimethiylphenyl) I-amino-tetrihydro-2-furtanone in a ratio of approximately 1:1 g of the 1:1 mixture of (aR,1'R) and 3-IN-(methoxyacety'L)- 3-chloro-2 ,6-dimethylphenyl) I-amino-tetrahydro-2-furanone is dissolved at elevated temperature in 0. !5 g of methyl ethyl ketone and, at reduced temperatur~e, the solution is inoc-utated with (aS,1'R)-3-(N-(methoxy- I L- _-_I~-LIIILI-.

16 acetyl)-N-(3-chloro-2,6-dimethylphenyl)]-amino-tetrahydro-2-furanone.

After leaving to stand at 0 0 C for three days, the resulting crystals are filtered off and dried. The crystalline product consists of pure (aS,1'R)-3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-aminotetrahydro-2-furanone.

Example P9: Preparation of the 1:1 mixture of (aR,1'R) and (aS,1'R) 3-[N-(methoxyacetyl)-N-(3-chloro-2 6-dimethylphenyl)]-aminotetrahydro-2-furanone from pure (aR,1'R) 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]-amino-tetrahydro- 2-furanone 0.2 g of (aR,I'R) 3-[N-(methoxyacetyl)-N-(3-chloro-2,6-dimethylphenyl)]sa amino-tetrahydro-2-furanone is mixed with 0.01 g of tetrabutylammonium 0 1 bromide and the mixture is maintained at from 160 to 180°C for 2 hours.

S0 oa The reaction mixture which crystallises upon cooling is triturated with OB 1 ml of water while cold, and is filtered and dried. The crystalline io product which is obtainable in quantitative yield consists of the 1:1 o o mixture of (aR,1'R) and (aS,1'R) 3-[N-(methoxyacetyl)-N-(3-chloro-2,6- 0 0 dimethylphenyl)]-amino-tetrahydro-2-furanone.

o.i° o Formulation Examples (throughout, percentages are by weight) 0 04 F 1 Emulsifiable concentrates a) b) c) S,,o compound of formula IIIa 25 40 50 calcium dodecylbenzenesulfonate 5 8 6 castor oil polyethylene glycol ether (36 moles of ethylene oxide) 5 04 G o tributylphenol polyethylene glycol ether (30 moles of ethylene oxide) 12 4 cyclohexanone 15 20 xylene mixture 65 25 20 Emulsions of any required concentration can be obtained from such concentrates by dilution with water.

I-

1 17 F 2 Solutions compound of formula liIa ethylene glycol monomethyl ether polyethylene glycol (mol. wt. 400) N-methyl-2-pyrrolidone epoxidised coconut oil petroleum fraction (boiling range 160-190°C) a) b) 0 10 0 70 20 d) 95 94 These solutions are suitable for application in the form of micro-drops.

a a a a a 4 Cu a a a 0 F 3 Granulates compound of formula IIa kaolin highly dispersed silicic acid attapulgite a) 5% 94 1% b) 10 90 The active ingredient is dissolved in methylene chloride, the solution is sprayed onto the carrier, and the solvent is subsequently evaporated. off in vacuo.

a" a F 4 Dusts compound of formula ilIa 0o:4 highly dispersed silicic acid talcum kaolin a) 2% 1% 97 b) 90 wa a e. a 4 04Q Ready-for-use dusts are obtained by intimately mixing the active ingredient.

the carriers with F 5 Wettable powders compound of formula lia sodium lignosulfonate sodium lauryl sulfate sodium diisobutylnaphthalenesulfonate a) 25 5% 3% b) 50 c) 75 6 10 18 octylphenol polyethylene glycol ether (7 to 8 moles of ethylene oxide) 2 highly dispersed silicic acid 5 10 10 kaolin 62 27 The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of the desired concentration.

Biological Examples 1. Action against Phytophthora infestans on tomato plants 0 0 to e S' a) Residual protective action at oa.e After a cultivation period of 3 weeks, tomato plants were sprayed with a 0 0 spray mixture (0.02 active ingredient) prepared as described above from S a wettable powder formulation of the test compound. 24 hours later, the treated plants were infected with a sporangia suspension of the fungus.

Evaluation of the fungus attack was made after incubating the infected "u plants for 5 days at 90-100 humidity and 20 0

C.

oa b) Systemic action 0IJ After a cultivation period of 3 weeks, tomato plants were watered with a spray mixture (0.002 active ingredient based on the volume of the soil) prepared as described above from a wettable powder formulation of the 0u 0 test compound. Care was taken that the spray mixture did not come into o" contact with the parts of the plants that were above ground. 48 hours later, the treated plants were infected with a sporangia suspension of the fungus. Evaluation of the fungus attack was made after incubating the infected plants for 5 days at 90-100 relative humidity and 20 0

C.

The compound of formula IIIa was found to be fully effective: fungus attack was 0-5 2. Plasmopara viticola on vines (vine seedlings, cv. Gutedel (Chasselas) pots each containing 1 plant/test compound), r 19 a) Residual protective foliar application vine seedlings are sprayed with a spray mixture prepared from a formulation of the test compound, and are infected 1 day later with a sporangia suspension (200,000 sporangia/ml) of P. viticola. Incubation is carried out at 20 0 C in a greenhouse compartment; a 14-hour incubation phase at 100 relative humidity is followed by 4 days at 75-85 and, finally, to induce sporulation of the fungus, a further night at 100 After the 6-day incubation period, the fungus attack is evaluated.

b) Systemic action 5-week-old vine seedlings are watered with a spray mixture prepared from t *1 a formulation of the test compound. 3 days later the plants are infected with a sporangia suspension (200,000 sporangia/ml) of P. viticola, The test is carried out as described in a).

9Q 0 0 0 Fungus attack was confined to 0-5 with the compound of formula IIIa.

3. Systemic action against Pythium debaryanum on Zea mays a O a a4 The fungus was cultivated on carrot chip nutrient solution and added to a o"o mixture of soil and sand. The soil infected in this manner was used to fill flower pots and maize seeds were sown therein. Immediately after sowing, an aqueous suspension (20 ppm active ingredient of formula IIIa based on the volume of the soil) of a wettable powder formulation of the E test compound was poured into the soil. The pots were then placed in a greenhouse for 3 weeks at about 200C. During that period, the soil was kept uniformly moist by light spraying. In evaluating the test, the number of emerged maize plants and the number of healthy and diseased plants were determined.

The number of emerged and healthy plants was more than 90

Claims

1. A orocess for the preparation of (aS,1'R)-3-[N-(ncyl)-N-(3-chlorophenyl)]-amino-tetrahydro-2-furanones of formula I Cl I N W 7 I \R2 9k-R3 wherein each of R 1 and Rz, independently of the other, is methyl or ethyl to and R3 is methyl, chioroethyl, methoxymethyl or cyclopropyl, which 0 process comprises 0 0 a) oxidiging an a-phenylamino-y-butyrolactono of formula V /Ri k 0<43 C-? wherein Ri and R 2 are as defined above, to give a 3-(penylamino)-2, 5 dihydro--furaoone of formula IV /RI 0\ wheein Ri and R 2 ae as defined above, b) acylating the: laer with a. carboxylc: aid hlde or CbXY~iCi nhd anhydride of formula VI R 3- x (VI) rpr 21 wherein R 3 is as defined for formula I and X is chlorine, bromine or the radical R 3 COO-, to give a 3-[N-(acyl)-N- (phenyl)]I-amino-2, 5-dihydro-2- furanone of formula III 0 R2 9 Bi.u (III), wherein Ri, R2 and R3 are as defined above, c) hydrogenating the resulting product with hydrogen in the ptesenc of an enantioselectively active catalyst to give a 3-(N-(acyl)-N- (phenyl)J-amine-tetrnhydre-a-fi ramone of fTrmnla II 0 0 00 0 converting the hydrogeni~rd product by chlorination into the (0,1'R; aS,I'R) diasereoners o\mr of the 3-(N-(aCyl)-N-(3-Chlo 0 phenyl) 1-amino-tet bydro-2,,-'4urononos of formula I, o 0e) and isolating, the (as,1'R) 0nafltiomeV therefrom by crystIllistion from a4 solttontf

2. A process according to clmim If wher'ein RI and R2 are mothyl, R3 is mothoymethyl and X is chlorine,

3. A process according to claim 2, which Comprises carrying, out the oxidation of the compound of formIula Va to give the compound of formula Iva F-- c-- 22 CH3 0 NH-- CH 3 (Va) CH 3 0 C11 3 (Iva) with manganese dioxide as oxidising agent in a solvent at 40-140 0 C,

4. A process according to claim 3, which comprises carrying out the oNdation in toluene at 85-.112 0 C 00 00a 0. 5, A process according to claim 2, which comprises carrying out the 00 0 oxdation With a cprium(iV) compound as Qxidising agent, 6, A process according to Claim 2, which comprises a) ozsdising the compound of forula caamn 3 with 4 peio~de Ql a peracid in a solvent at from -0Q" to +40'0 under atmospheric pressure to give [N-(hyckoxy)-N-;(2 6dmthyiphenyl) 1-mino-tet hy 2-urnone and C a0 converting the latter b y rmoving the elements of water into the compound of formula Vti b) carrying out the aqylation of the compound of fornmwla IVa with an, C exdes of 50-$00 Z of the theoretical amount of the aompound of formula Via to give the compound of fomula Illa CIIbOCu~gCI /rr 11ta with the hydrgn h :tido producod s byprsodQut being driven off by boiling under reduced preeuru at 4Q-600o0 4) tarrying out the hydrov.Qnatlon of the compound of fotnulae ~ia to give t h coantiomor of the tMpoun4d: of formula Ila 23 0\ CH3 C- 7N (Ha), CH 2 0CHI CHa 1 in the presence of catalytic amounts of rhodium compounds of formula VII or VIa [xRhYZ] (VII) or [XRhY]A (VIIa) wherein X represents two olefin ligands or one diene ligand, Y is a Schiral dinhosphine in which the setondary phosphine groups are linked by 2 to 4 carbo, 4 atoms and that forms, together with the Rh atom, a 6-or

7-membered ring, or Y is a chiral diphosphinite in which the phosphinite groups are linked by 2 carbon atoms .nd that forms, together with the Rh atom, a 7-membe ring, Z is chloride, bromide or iodide, and A is the anion of an oxygen or complex acid, in an alcohol as solvent, under o 01-13Q bar at from -20 to +70 0 C, d) carrying out the clEorination of the compound of fotmula Ha to give the compound of formula Ia (Ia) u" a CM /*oCI with elemental chlorine, and e) carrying out the isolabion of the (aS,1'R) enantiomer of formula Ia from methyl ethyl ketone as solvoant. 7. A process according to claim 6, which compri ss carrying out the oxidation with m-chloroperbenzoic acid as oxialsing agent in tetra- hydrofuran at Q-10oC and carrying out the hydrogenation in the presence of 0.002-10 mol. in each case of bis-norbornadienyl-rhodium(I) tetra- -24 fluoroborate anld (4R,5R)-(-)-4,5-birw-(diphenylphosphinomethyl)-2,2-di- methyl-1,3-dioxolane, based on the compound of formula Mia, in methanol under 1-70 bar at 0-50'C.

8. A process according to claim 6, which comprises carrying out the oxidation with m-chloroperbenzoic acid as oxidising agent in dichioro- methane at 0-10 0 C and carrying out the hydrogenation in the presence of 0.002-10 mol. in each case of bis-norbornadienyl-rhodilum(I) tetra- fluoroborate and (4R,5R)-(-)-4,5-bis-(diphenylphosphinomethyl)-2,2- dimethyl-1,3--dioxolane, based on the compound of formula lila, in methanol under 1-70 bar at 0-50'C. 9, A process acccording to claim 2, which comprises oxidising the compound of formula Va, claim 3, with a peroxide or a peracid in a solvent at from ~1ot 4 0 ne tospheric pressure to give N-[N-(hydro~y)-N-(2,6-dimethylphenyl) J-amino-tetrahydro-2-furanone and converting the latter by removing the elements of water into the o compound of formula IVa, b) carrying out the acylation of the compound of formula IVa with an o ,excess of 50-500 of the theoretical amount'of the compound of formula Vla to give the compound of formula Mia 042 CH Cz03i CH3 Vla IIla with the hydrogen chloride ptoduced as by-product being driven off by boiling under reduced pressure at 40-60'4C, car .ying out the hydrogenation of the compound of formula III,,, claim 6, to give the enantlomer of the compound of formula 11a, claim 6, in the presence of catalytic amounts of a RU (R)-2,2'-bis(diarylphosphino)-i,1'-binaphthyl salt of formula VIlla or~ a Ru (S)-2,2'-bis(diarylphosphino)-1,1'-binaphthyI salt of formula VIlIb Ru 2 -Ru 2Z *R4/P R 4 4 4 (VIlla) (VIlIb) wherein R 4 is a phenyl radical that is unsubstituted or mono subs titu ted by Cl-Ci4a!hYl or by methoxy, or is a 1- or 2-naphthyl radical, and Z- is either an anion of the formula RSC00-, wherein R 5 is CI-Csalkyl or CF 3 for is the trifluoromethanesulfonate anion, in an alcohol as solvent, .under 0,1-150 bar at -20 to +70'C, and carrying out the chlorination. of the compound of formula Ila i:o give the compound of formula claim 6, with elemental chlorine. A process according to claim 9, which comprises carrying out the hydrogenation in the presence of 0.002-10 inol. of Ru or bis(dipbenylphosphino)-1,1'-binaphthyl d1iiicetate, based on the compound of formula Ila, in methanol under 1-7C. I 1 ar at 0-50'C. S 11, A process for the preparation of the (aR,1'R; aS,1'R,) diastereo- isomeric mixtures of 3- N- (acyl) (3-chlo rophenyl) I-amino- te trahydro- '-furanones of formula I, claim 1, which comprises a) oxidising a 2-phenyl-aniino-y-butyrolactone of formula V, claim 1, to give a 3-(phenyl-amino)-2,5-dihydro-2-oxofuran of formula IV, cla, m 1, b) converting the latteL' with a carboxylic acid halide or a carboxcylic acid anhydride of foiinula VI, claim 1, into a 3-[N-(methoxyacetyl)-N- (phenyl)IJ-arino-2,5-dihydro-'2-furanone of formula III, claim 1, c) hydrogenating the resulting product with hydrogen in the presencQ of ar active catalyst to give 3-[N-(acyl)-N-(phenyl)]I-amino- tetrahydro-2-furanonG of formula II, claim 1, -H r 26 d) chlorinating the hydrogenated product and isolating the resulting (aR,1'R; aS,1'R) diastereoisomeric mixture of the compound of formula I.

12. A process according to claim 11, wherein R 1 and R2 are methyl, R 3 is methoxymethyl and X is chlorine.

13. A process according to claim 12, which comprises a) carrying out the oxidation of the compound of formula Va, claim 3, with m-chloroper'enzolc acid as oxidising agent in tetrahydrofuran at 0-10°C and removing the elements of water from the resulting N-hydroxy derivative, b) carrying out the acylation of the compound of formula IVa with an excess of 50-500 of the theoretical amount of the compound of formula Via, claim 6, to give the compound of formula Ilia, claim 6, with the hydrogen chloride eo produced as by-product being drived off by boiling under reduced pressure at

40-600C, c) carrying out the hydrogenation of the compound of formula Ilia in an alcohol solvent, under 0.1 to 150 bar at from -20 0 C to +70 0 C to give the enantiomer of the compound of formula Ila, claim 6, in the presence of catalytic amounts of a rhodium compound of formula VII or Vila, claim 6, d) carrying out the chlorination of the compound of formula Ila to give the compound of formula la, claim 6, with elemental chlorine. 14. A process according to claim 12, which comprises carrying out the oxidation with m-chloroperbenzoic acid as oxidising agent in dichloromethane i, at 0-100C and removing the elements of water from the resulting N-hydroxy derivative. I 15. A process according to claims 13 and 14, which comprises carrying out the hydrogenation in the presence of 0.002-10 mol. in each case of bis- norbornadienyl-rhodlum(l) tetrafluoroborate and (diphenylphosphlnomethyl)-2,2-dlmethyl-1,3-dioxolane, based on the Scompound of formula Ilia, in methanol under 1-70 bar at 0-500C, F I x 1 i i i i Ci- i Ll~i r~L~ i 27 16. A process according to claim 12, which comprises a) carrying out the oxidation of the compound of formula Va with m-chloroperbenzoic acid as oxidising agent in tetrahydrofuran at 0-10 0 C and removing the elements of water from the resulting N-hydroxy deriva- tive, b) carrying out the acylation of the compound of formula IVa with an excess of 50-500 of the theoretical amount of the compound of formula VIa, claim 6, to give the compound of formula IIIa, claim 6, w'.th the hydrogen chloride produced as by-product being driven off by bo.ilng under reduced pressure at 40-60 0 C, c) carrying out the hydrogenation of the compound of formula IIIa to give the enantiomer of the compound of formula IIa, claim 6, in the presence of catalytic amounts of a Ru (R)-2,2'-bis(diarylphosphino)- 1,1'-binaphthyl salt of formula Villa or a Ru (S)-2,2'-bis(diarylphos- phino)-1,1'-binaphthyl salt of formula VIIIb 0 4 0 0 0 0 4 0 0 0 @0000 0 0 oU 0 0 0 0( ro o0 0 00 0 00u i I 4 R4 8/ \,P I \Ru \.4 2 Z I Ii (VIIIa) (VIIIb) wherein R 4 is a phenyl radical that is unsubstituted or monosubstituted by Ci-C4alkyl or by methoxy, or is a or 2-naphthyl radical, and Z- is either an anion of the formula RsCOO-, wherein Rs is Ci-C6alkyl or CFs, or is the trifluoromethanesulfonate anion, in an alcohol as solvent, under 0.1-150 bar at -20 to +700C, and d) carrying out the chlorination of the compound of formula IIa to give the compound of formula Ia, claim 6, with elemental chlorine. P 28 17. A process according to claim 16, which comprises carrying out the hydrogenation in the presence of 0.002-10 mol. of Ru or bis(diphenylphosphino)-1,1'-binaphthyl diacetate, based on the compound of formula Ilia, in l- under 1-70 bar at 0-50 0 C. 18. A process for the preparation of the (aS,1'R; aR,1'R) diastereoiso- meric mixture of the compound of formula I, claim 1, from the (aR,1'R) enantiomer of the same compound, which comprises heating the latter at from 160 to 180 0 C for from 1 to 3 hours. oo 19. A process according to claim 18, which comprises carrying out the 0 o0 heating in the presence of tetrabutylammonium bromide. 0 0 °oo 0 20. A proceas for the preparation of 3-(phenylamino)-2,5-dihydro-2- o a o r furanones of formula IV, claim 1, which comprises oxidising a 2-phenyl- o amino-y-butyrolactone of formula V, claim 1, with an oxidising agent and 0 o isolatiiig the reaction product. 0000 a 21. A process according to claim 20, which comprises carrying out the o*c 0 oxidation with m-chloroperbenzoic acid as oxidising agent in tetrahydro- furan at 0-10 0 C and removing the elements of water from the resulting N-hydroxy derivative. 22. A process according to claim 21 for the preparation of 3-[N-(2,6-di- 000oo Son, methylphenyl)]-amino-2,5-dihydro-2-furanone of formula IVa, claim 3. o o 00 23. Compounds of formula IV, claim 1. 24. 3-[N-(2,6-dimethylphenyl)]-amino-2,5-dihydro-2-furanone of formula IVa, claim 3, according to claim 23. A process according to claim 20, which comprises carrying out the oxidation with m-chloroperbenzoic acid as oxidising agent in dichloro- methane at 0-10 0 C and removing the elements of water from the resulting N-hydroxy derivative. 0 'o 29 26. A process for the preparation of 3-[N-(methoxyacetyl)-N-(phenyl)]- amino-2,5-dihydro-2-furanones of formula III, claim 1, which comprises reacting a compound of formula IV, claim 1, with a compound of formula VI, claim 1, and isolating the reaction product. 27. A process according to claim 26, wherein RI and R 2 are methyl and X is chlorine. 28. A process according to claim 27, which comprises carrying out the reaction with an excess of 50-500 of the theoretical amount of the compound of formula VIa, with the hydrogen chloride produced as by- product being driven off by boiling under reduced pressure, at 40-600C. 29. Compounds of formula III, claim 1. 30. 3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-amino-2,5-dihydro-2- furanone of formula liIa o 0 00 44 4 04 0 04 00 44 4 4 4 0 0 0 5 CH 3 -N- \CH cocH3 ~CH 3 9C 2 0H (Ilia), 4 4 4 44a u according to claim 29. 31. A process for the preparation of (1'R)-3-[N-(acyl)-N-(phenyl)-amino- tetrahydro-2-furanone derivatives of formula II, claim 1, which comprises hydrogenating a compound of formula III, claim 1, with hydrogen in the enrioasletcivey presence of c 4lc!y active catalyst. 32. A process according to claim 31, wherein RI and R 2 are methyl and R3 is methoxymethyl. 33. A process according to claim 31, which comprises carrying out the hydrogenation in the presence of catalytic amounts of a rhodium compound of formula VII or VIIa, claim 6. 34. A process according to claim 33, which comprises carrying out the hydrogenation in the presence of catalytic amounts of bis-norbornadi- enyl-rhodium(I) tetrafluoroborate and (4R,5R)-(c)-4,5-bis(diphenyl- phosphinomethyl)-2,2-dimethyl-1 ,3-dioxolane ,n R==saLAet, under 1-70 bar at 0-50 0 C. A process according to claim 31, which comprises carrying out the hydrogenation in the presence of catalytic amounts of a Ru or (S)-2,2'-bis(diasylphosphino)-1,1'-binaphthyl salt of formula VIIIa or VIIb /R Pit *R4 R4 R' R4 a lli II I Ru 2Z 2Z r~ pa raoa I II I j 2 I \Ru R (VIIIa) (VIIIb) wq wherein Rq is a phenyl radical that is unsubstituted or monosubstituted 0 by Ci-c4alkyl or by methoxy, or is a 1- or 2-naphthyl radical, and Z- is either an anion of the formula R 5 000-, wherein Rs is Ci-Csalkyl or CF3, or is the trifluoromethanesulfonate anion, in an alcohol as solvent, under 0.1-150 bar at -20 to +70 0 C, and carrying out the chlorination of the compound of formula IIa to give the compound of formula Ia, claim 6, q with elemental chlorine. o 0 4 oo 0 36. A process according to claim whi.h comprises carrying out the hydrogenation in the presence of 0,002-10 mol. of Ru or (S)-2,2'-bis(diphenylphospbino)l ,1'-binaphthyl diacetate, based on the rr~ aj'AQMRo\ compound of formula IlIa, in 3-Alent under 1-70 bar at 0-50'C. 37. A process for the preparation of the (aS,l'R, aR,1'R) diastereoiso- meric mixture of formula 1, claim 1, which comprises reacting the compound of formula I with a chlorinating agent. 38. A process according to claim 37, which comprises using chlorine as the chlorinating agent. 31 39. Fungicidal compositions containing, as active ingrediant, 0.1-95 %of 3-IN-(methoxyacetyl)-N-(2,6-dimethylphenyl) ]-amino-2,5-dihydro-2-furanone of formula IIla, claim 30, together with a suitable carrier. A method of controlling phytopathogenic microorganisms, which comprises applying to the plant or to the locus thereof a microbicidally effective amount of 3-IN-(methoxyacetyl)-N-(2,6-dimethylphenyl)1-amino- 2,5-dihydro-2-furanone of formula IlIa, claim 41, A process for the preparation of a (aS,l'R)-3-EN-(acyl)-N-(3-chlorophenyl)]-amino-tetrahydro-2-furanone substantially as herein described with reference to Example P8. 42, A process for the preparation of a diastereolsomeric mixture of (aR,l'R) and (aSXlR) 3-EN-(methoxyacetyl)-N-(3-chloro-2,6-dimethyl- f phe nyl -ami no-te trahydro-2-f uranone s ubs tant iall Iy a s here in de scr ibed 'dith reference to Example P7 or P9, DATED this SIXTEENTH day of JUNE 1989 Ciba-Geigy AG Patent Attorneys for the Applicant SPRUSON FERGUSON