IL98742A - Methyl-2-(substituted methyl)-alpha-(dimethoxymethyl)-benzeneacetate - Google Patents

Description

This is a divisional application of Application 8512Z filed on It relates to derivatives of propanoic acid useful as intermediates in the preparation of Application 85122 describes compounds having the formula and stereoisomers wherein is a heteroaryl moiety which is optionally substituted by one or more alky hydroxy cycloalkyl alkyl heteroaryl phenyl 1n which the alkyl moiety is optionally substituted with heteroaryl heteroaryl phenyl heteroaryl or or substituents on the heteroaryl moiety of R when they are in adjacent may join to form a thianthrenyl or phenoxathi fused phenyl or heteroaryl moieties comprised in any of the foregoing substituents are substituted by one or more alkynyl heteroaryl alkyl in which the alkyl moiety is optionally substituted phenyl heteroaryl phenox wherein phenyl or heteroaryl moieties comprised in any of these substituents are optionally substituted by one or more cycloalkyl or and are independently phenyl or phenyl the phenyl or phenyl groups being optionally substituted alkyl or the heteroaryl moieties or or Y 1s sulphur or NR 3 and which may be the same or are alkyl or X is Cj nitro or n 1s 0 or an of 1 to is sodium or This invention as chemicals for the preparation of the compounds of formula a compound of formula 1 9 wherein R Y and n have the meanings defined In one aspect the invention provides a compound of formula wherein Y is In another aspect the invention provides a compound of the formula as defined above in which X 1s The compounds of formula contain at least one double and are sometimes obtained in the form of mixtures of geometric these mixtures can be separated into and Application describes such and mixtures thereof in all proportions including those which consist substantially of the and those which consist of the The individual isomers which result from the substituted double bond of the propenoate group are identified by the commonly used terms and These terms are defined according to the system which is fully described in the literature for J Organic 3rd page 109 et Usually one isomer is more active fungicidally than the the more active isomer usually being the one wherein the groups and are on opposite sides of the olefinic bond of the propenoate group Substltuents which may be present on the optionally substituted heteroaryl moiety include one or more of the methyl and alkenyl alkoxy alkenyloxy and and alkylthio alkyl phenethyl and phenyl in which the moiety is optionally substituted heteroaryl or heteroaryl or phenyl or or or which and are g cycloalkyl phenyl or phenyl substlutents which may be present the phenyl and heteroaryl moieties include one or more of those heteroaryl substltuents described Immediately and the heteroaryl moieties are as defined When any 7 1 4 of the substituents R R and X are alkyl or the alkyl moiety can be 1n the form of straight or branched that the moiety may be or or or Other references herein to alkyl and alkoxy carry the same 9 When any of the R R R and X are these groups can be 1n the form of straight or branched chains where may have either the or the Examples of such groups are and and Other references herein to carry the same It is preferred that R 2 and R3 are both hydrogen and that is hydrogen or When n is 2 or the substltuents X may be the same or It is generally that n is 0 or In another aspect the provides compounds of the formula in which B is N or Y has the meaning given p 1s 0 or an integer of 1 to 3 when B is or 0 or an integer of 1 to 4 when B 1s and A halo fluoro or alkyl methyl or particularly or alkoxy or Compounds are preferred 1n which the basicity of the nitrogen of the heterocyclic ring Accordingly it preferred that Y Is attached to a position ortho to a ring nitrogen or a substltuent A Is attached to a position ortho to a ring nitrogen or When p 1s 2 or preferred that the which may be the same or are methoxycarbonyl or Examples of combinations of the substltuents A when p 2 or more are and when is and The compounds listed 1n Table I which follows are of the compounds of formula which may be prepared from the compounds of the COMPOUND X R2 R3 Isomer 1 H H H E 2 H H H E H H 3 4 H H H E 5 Pyrimid 1 H H H E 6 H H H E 7 P H H H E 8 H H H E 9 H E H H H E H H H E 12 ethoxy H H H E H H H E H H H E 15 H H H E TABLE I C X R2 16 H H H E 17 H H H E 13 3 f luorcmethy pyr H H H E 19 H H H E 20 5 thy lpyr imid i 1 H H H E 21 H H E 22 H H H E 23 f luorcmethy 1 pyr H H H 2 4 H H E 25 H H H E 26 3 f luorcmethy 1 H H H E 27 H H E 28 6 H H H E 2ff H E 30 luoropyr H H H E 31 f H H H E TABLE I TABLE I X R2 R3 Is 48 H 49 1 H H H 50 f luoropyr H H H 51 richloramethy 1 H 52 1 H H H 53 H H 5 55 H H 56 H H H H H H H 59 H H H H H 61 H H H 62 5 H H H TABLE I TABLE I TABLE I X R2 71 H H E 72 H H H E i 73 H E 74 H H H E H H H E 75 TAELE I Isane E E TAELE I TAELE I TABLE I of singlet olefinic proton on group Solvent CDCI3 unless otherwise Geometry of Also Illustrative of compounda which may be prepared from the compounds of the invention are the compounds of the in which and x have the same combinations 5 of meanings each of the linked compounds in Table I when Y of compound of Table IX corresponds to 10 Compound 1 of Table I respect to their meanings of R3 and TABLE Chemical shift of singlet from olefinic proton on methoxypropenoategtoup from Solvent unless otherwise Geometry of Further tlluatrative of compounds which may be prepared from the compounds of the invention are the compounds of the in which R3 and X have the same combinations of meanings as each of the corresponding compounds in Table I where Y of Compound and R4 is hydrogen and TABLE TABLE SELECTED PROTON NMR DATA Table HI shows selected proton NMR data for certain compounds described in Tables I and Unless otherwise compounds are from Table Chemical shifts are measured in ppm from and was used as solvent The following are used br broad t triplet ppm parts per s singlet q quartet million d doublet m TABLE COMPOUND 07 COMPOUND 1 of Table The compounds of formula may be pcepared by the steps shown in Scheme Throughout Scheme the terms Y and n are as defined Each of the described in Schemes and II at a suitable temperature and though not in a suitable As shown in Scheme the compounds of formula can be from acetals of formula the compounds of the by elimination of methanol under either acidic or basic Examples of reagents or reagent mixtures which can be used for this transformat on ate lithium potassium hydrogen sulphate T and H chemical Communica and references and often the presence of Lewis acid such as titanium tetrachlo for and L chemical Communlca The acetals of formula the compounds of the can be prepared by treatment of methyl silyl ketene acetals of formula wherein is an with or in the presence of a Lewi3 acid such as ticanium for K M Csaki and T Chemistry Methyl ketene acetals of formula can be pcepared from phenylacetates of formula by treatment with a base and a halide of formula R3sicl or such as or a base as and a ialkylsilyl trlflate of formula for C F Chen and Y J Chemistry It is not always necessary to isolate the intermediates and under appropriate compounds of formula may be prepared from phenylacetates of formula in by 2k the successive addition of suitable reagents listed Reference is made to which discloses the compound and other methyl It also describes their method of preparation from the corresponding acetals and the preparation of the acetals Scheme Scheme II shows approaches by which phenylacetates of formula may be prepared from of formula Thus of isochromanones of formula with species of formula wherein and Y are as defined above and is a metal as sodium or gives phenylacetic acids of formula The phenylacetic acids may be converted into phenylacetates by standard methods described in the isochromanones of formula may be converted into phenylacetates formula wherein Z is a halogen atom ae using HZ in This transformation may also be accomplished in 2 steps if the isochromanone is treated with HZ in a and the resulting phenylacetic acid is then esterified using standard procedures for I and J 79 138 Che and G M F Y G Perron and R D Disc 128526 Phenylacetates of formula may be converted into phenylacetates of formula bv treatment with species wherein Y and M are as defined Phenylacetates of formula and the cor esponding phenylacetic acids of formula may also be prepared by numerous other methods described in the chemical For several useful methods are described by D C K E B J P saville and M R 1353 and D C K E P C M R stillings and many of the methods described for the preparation of esters and acids by A Cousse and G are also applicable to the preparation of phenylacetates of formula and phenylacetic acids of formula using appropriate precursors wherein the substituents and X are already Scheme II may be prepared by methods described in the literature for V V and M 7h The following Example illustrates the preparation of an intermediate for use in the Throughout the the term refers to diethyl magnesium sulphate was used to dry and solutions were concentrated under reduced Reactions involving sensitive intermediates were performed under an atmosphere of nitrogen and solvents were dried before where Infrared and data are no attempt is made to list every absorption in all NMR spectra were recorded using The following abbreviations are used NMR nuclear magnetic resonance s singlet infrared m EXAMPLE 1 This Example illust preparation of methyl an intermediate for the preparation of phenyl was added to a solution of potassium hydroxide in a little and the resulting mixture was stirred for an hour at room temperature and 15 minutes at was added to the reaction mixture and it was heated in an flask at for 5 Λ further of ophenol was then an was fitted to the and heating at 150eC was continued for a further 6 After the reaction a viscous brown was dissolved in a mixture of ethyl acetate and dilute hydrochloric The organic and aqueous layers were separated the latter wa6 extracted with further ethyl The combined ethyl acetate layers were washed with water dried and concentrated to give a viscous brown oil This oil was dissolved in methanol a drops of concentrated hydrochloric acid were and the solution was heated under reflux for 6 After the mixture was poured into water and extracted with The extracts were washed successively with aqueous sodium hydroxide and then dried and concentrated to give methyl Jphenylacetate as an 1733 delta EXAMPLE 2 This Example illustrates the preparation of methyl an intermediate for the preparation of hoxy was added to a solution of potassium hydroxide in a little and the resulting mixture was stirred for an hour at room temperature and 15 minutes at was added to the reaction mixture and it was heated in an flask at for 5 A further of was then an air condenser was fitted to the and heating at was continued for a further 6 After the reaction a viscous brown was dissolved in a mixture of ethyl acetate and dilute hydrochloric The organic and aqueous layers were separated and the latter was extracted with further ethyl The combined ethyl acetate layers were washed with water dried and concentrated a viscous brown oil This oil was dissolved in methanol a few drops of concentrated hydrochloric acid were and the solution was heated under reflux for 6 After the mixture was poured into water and extracted with The extracts were washed successively with aqueous sodium hydroxide and then dried and concentrated to give methyl chlorophenoxymethyl Jphenylacetate as an IR 1733 NMR delta insufficientOCRQuality

Claims (1)

1. 31 A compound of the wherein s a heteroaryl moiety which optionally substituted by one or more which the alkyl moiety is optionally substituted with heteroaryl phenyl phenyl heteroaryl phenox or or on the heteroaryl moiety of when they are adjacent may join to form a thianthrenyl or phenoxathiinyl fused phenyl or heteroaryl moieties comprised any of the foregoing substltuents are optionally substituted by one or more cycloalkyl which the alkyl moiety Is optionally substituted with heteroaryl heteroaryl or wherein phenyl or heteroaryl moieties comprised any of these substituents are optionally substituted by one or more oft C2 4 cycloalkyl or and are independently cycloalkyl phenyl or the phenyl or phenyl groups being optionally substituted with alkyl or the heteroaryl moieties or quinoxalinyl or Y 1s sulphur or and which may be the same or are nitro or n is 0 or an of 1 to A compound according to claim 11n which Y A compound according to claim 1 or 2 in which heteroaryl optionally substituted by one or more cycloalkyl phenyl in which the alkyl moiety is optionally substituted heteroaryl phenyl heteroaryl or 1n which and are C3 cycloalkyl phenyl or the phenyl or heteroaryl of any of the 33 foregoing substltuents being optionally substituted 1n the same way as and heteroaryl or isoquinol qu1noxal1ny1 or A compound according to claim 1 1n which X Is Λ compound of the formula in which B is N or Y has the meaning given claim p 1s 0 or an integer of 1 to 3 when B is or 0 or an integer of 1 to 4 when B is and A 1s alkoxycarbonyl or A compound according to claim 5 which Y attached to a position ortho to a ring nitrogen or a A 1s attached to a ortho to a nitrogen or HOROWITZ ε AGENT FOR THE APPLICANT insufficientOCRQuality