IL96571A - Alkyl 2-(substituted phenyl) acrylates - Google Patents

Description

ALKYL ACRYLATES is a divisional application of Application 82127 filed on 7 April It relates to which may be used in the preparation of acrylic acid derivatives useful in and to processes for preparing Application 82127 describes having the formula and stereoisomers vherein V is a substituted pyridinyl or a substituted pyrimidinyl group linked to A by any of ring carbon V is by halogen or pyrimidinyl or tetrazolyl ring optionally linked to V through an oxygen or vherein is 1 or Y and the or are hydrogen or halogen 6 7 or p is 1 or and R vhich same or are and vhich are same or are hydrogen or phenyl or any of the foregoing alkyl moieties may be optionally substituted with C phenyl or any of the foregoing alkenyl moieties may be optionally subsituted by any of the foregoing pynmidinyl or tetrazolyl ring moieties may be optionally substituted with one or more of C C C or and are independently C C CM C34 phenyl or benzyl the phenyl and benzyl being optionally substituted with CM alkyl or CM A is either an oxygen atom or wherein n is 1 or R8 is hydrogen or a metal provided that when W is a monosubstituted pyridinyl group wherein the substituent is trifluoromethyl A is X is and and R2 are both Y and Z are not both Y is not C benzoyloxy or amino optionally substituted by phenyl or C if Z is and Y and Z together are not or This invention as intermediate chemicals for the preparation of the compounds of formula wherein is compounds of and stereoisomers wherein M is the residue of an inorganic A is either an oxygen atom or wherein n is 1 or Y and which the same or are hydrogen halogen or or p is and R2 independendy and which are the same or are hydrogen or C34 any of the foregoing alkyl moieties may be optionally substituted with phenoxy or carboxyl any of the foregoing alkenyl moieties may be optionally substituted by any of the foregoing phenyl moieties may be optionally substituted with one or more of CM CM CM or and are independently C C phenyl or the phenyl and benzyl being optionally subsituted with C alkyl or CM The compounds of the invention contain at least one double and are sometimes obtained in the form of mixtures of geometric these mixtures can be separated into individual and this invention embraces such isomers and mixtures thereof in all proportions including those which consist substantially of the and those which consist substantially of the The individual isomers which result from the unsymmetrically substituted double bond of the 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 wherever present as a group or moiety and can be in the form of straight or branched and contain 1 to preferably 1 to carbon examples are or and butyl or and which are are preferably particularly It is particularly preferred that and R2 are both Halogen wherever referred to are particularly chlorine or bromine atoms and especially fluorine or chlorine Cycloalkyl for and for Alkenyl and alkynyl groups contain 2 to preferably 2 to carbon atoms in the form of straight or branched Examples are allyl and is preferably phenylethyl or phenyl and includes Substituents which may be present in any substituted phenyl moiety include one or more of the alkyl methyl and C alkoxy alkylthio C pehnylethyl and phenyl alkoxy in which and independently C C phenyl or the phenyl and benzyl groups being optionally substituted with CM alkyl or C and groups include particularly trihalomethyi and especially trifluoromethyl where otherwise In one aspect the present invention provides a compound of formula wherein and A are as defined and Y and which are the same or are chlorine or bromine or CM C benzyloxy or wherein the alkyl moieties of any of the foregoing are optionally subsduted with one or more C alkoxy chlorine or bromine hydroxy or carboxyl and wherein the phenyl moieties of any of the foregoing are optionally substituted with one more chlorine or bromine CM C hydroxy or carboxyl and and which the same or are C alkyl both In another aspect the present invention provides a compound of formula wherein A is It is preferred that A is Y and Z all hydrogen and that and R2 are both methyl It is preferred that M is an alkali atom A preferred compound of formula is the potassium salt of having the The compounds listed in Tables II and III vhich follow are illustrative of the compounds of formula vhich can be prepared from the compounds of the TABLE I Melting O Point H H H H H H H H H H H H H H H H H H H H H H H H H H H gum TABLE I ound Melting W X Y Z Point H H H H H H li H H H H H H H H H H H H H H H H H H H H H H H H gum 20 H H H H H H H H H H H H TABLE I Ccrnpound Melting Ole w X Y Z Point H H H 25 2 H H H 24 H H H H H H H H H H H H H H H H H H H H H H H H H H H 35 H H H 6 H H H I Ccrpound Melting w X Y Z Point 27 6 H H H 38 6 H H H 6 H H H Oil Mo H H H 2 H H H 2 H H H H i 2 H H H 2 H H H 2 H H H 3 H H H 3 H H H 3 H H H 3 H H H TABLE I TABLE I Compound Melting W X Y Z Point 2 H H H 2 luoromethyl H H H 2 H H H 5 H H H 5 H H H 5 H H H 5 H H H 5 luoromethyl H H H 5 H H H 6 H H H 6 H H H H H H 6 H H H 6 luoromethyl H H H H H H 2 H H H TABUS I TABLE I Compound Melting w X Y Z Point 5 H H H H H H 3 H H H H H H 3 H H H H H H H H H H H H 3 5 H H H H H H H H H H H H H H H TABLE I Compound Melting W X Y Z Point 5 H H H H H H H H H H H H 5 H H H 3 H H H H H H 5 H H H 5 H H H 5 H H H 3 H H H 5 H H H 5 H H H gum I Compound Melting X Y Z Point H H H gum H H H H H H H H H H H H H H H gum H H H 2 H H H H H H 5 H H H Oil TABLE I TABLE I Compound Melting W X Y Z Point 5 H H 5 H 5 H 5 H H 5 H H 5 H H 5 H H 5 H H H H Oil H H H 2 H H H Oil TABLE I Compound Melting W X Y Z Point 5 H H H 2 4 5 H H H 4 5 H H H 5 H H H 4 6 H H H 4 H H H 5 6 H H H 4 H H H H H 5 H H H It9 5 H H H 6 H H H I TABLE I Chemical shift of singlet from olefinic proton on group Solvent Geometry of TABLE II Melting Compound Y Z Point X 1 H H H 2 H H H 3 H H H 4 3 H H H 5 3 H H H 6 H H H 7 H H H 8 H H H 9 H H H 10 H H H II TABLE II TABLE II Compound Melting W X Y Z 43 l H H H 44 H H H 45 H H H 46 H H H 47 H H H 48 H H H 49 H H H 50 H H H 51 2 H H 52 H H H 53 H H H 54 3 H H H 55 H H H 56 3 H H H 57 3 H H H 58 3 H H H TABLE II Compound Melting W Y Z 59 3 H H H 60 H H H 61 H H H 62 H H H 63 H H H 64 H H H 65 H H H 66 5 H H H 67 5 H H H 68 5 H H H 69 H H H 70 H H H 71 5 H H H 72 2 H H H 73 H H H 74 2 H H H TABLE II Compound Melting W X Y Z Point 75 H H H 76 2 H H 77 H H H 78 5 H H H 79 H H 80 5 H H H 81 H H H 82 5 H H H 83 5 H H H 84 H H H 85 H 86 H H H 87 H H H 88 H H H 89 H H H 90 H H H TABLE II Compound Melting W X Y Z Point 91 H H H 92 H H H 93 2 H H H 94 2 H H H 95 H H H 96 H H H 97 H H H 98 H M H 99 H H 100 H H H 101 H H H 102 5 H H 103 5 l H H H Oil 104 5 H H TABLE II Chemical shift of singlet from olefinic proton on grou Solvent otherwise Geometry of TABLE III Chemical shift of singlet from olefinic proton on gro Solvent otherwise Geometry of The compounds of the invention having the general formula the compounds having the general formulae and may be used to prepare the acrylic acid derivatives as outlined in Scheme Throughout Scheme II the terms Y and Z are as defined L is a halogen atom or another leaving group which can sometimes be a nitro is hydrogen or a metal atom as a sodium and M is a protecting group for a phenol or thiophenol Compounds of general formula exist as geometric which may be separated by fractional crystallisation or Compounds of general formula can be prepared by reaction of compounds of general formula with compounds of general formula in the presence of a base as potassium if a transition metal or transition metal salt catalyst in a convenient solvent as of Scheme Compounds of general formula can be prepared from protected phenol or thiophenol derivatives of general formula by etandard deprotection procedures as set out the chemical literature of Scheme For phenols of general formula A is can prepared from benzyl ethers of general formula A is M is by in the presence of a suitable catalyst as palladium supported on Compounds of general formula in which the group M is a standard phenol or thiophenol protecting group at can be prepared by treatment of j phenylacetatea of formula with a base as sodium hydride or sodium and a formic ester methyl in a suitable solvent such as and at a suitable temperature of Scheme If a species of formula wherein L is at defined then added to the reaction compounds of formula may be obtained of Scheme If a acid is added to the reaction compounds of formula wherein R8 is hydrogen are the species of formula wherein R8 is a metal atom an alkali metal atom such as a sodium may themselves be isolated from the reaction Compounds of formula wherein R8 a metal atom can be converted into compounds of formula by treatment with a species of formula in a suitable Compounds of formula wherein R8 is hydrogen can converted into compounds of formula by successive treatment with a base as potassium and a species of formul Compounds of general formula can be prepared from esters of general formula by standard methods described in the chemical Esters of general formula can be prepared by esterification of compounds of general formula by standard methods described in the chemical Compounds of general formula can be prepared by standard methods described in the chemical U and and P D Clark and 0 M Mc Che 243 and references step The acrylic derivatives of formula prepared from the compounds of the invention are active as Application 8 The following Examples do not form part of this invention bu are included to illustrate a process by which compounds of the invention can be prepared by Throughout these the term refers to diethyl chromatography was carried out using eilica gel as the solid magnesium sulphate was used to dry and reactions involving or intermediates were performed under nitrogen and in dried here infrared and data are no attempt is made to list every Unless otherwise spectra were recorded using deuterochloroform The following abbreviations are used throughout ι g delta chemical shift ml s singlet Millimetres pressure d doublet of mercury maxima Melting point parts per million Nuclear magnetic resonance The word when used in the following Examples is a Trade or Service EXAMPLE This Example illustrates the preparation of 133 of Table acetic acid was added to a solution of hydrogen chloride in methanol from acetyl chloride and methanol The solution was stirred at room temperature for three hours and then allowed to stand overnight The resulting mixture was concentrated under reduced and the residue was taken up in ether and washed with an aqueous solution of sodium bicarbonate until effervescence The ethereal solution was dried and then concentrated under reduced pressure and the resulting solid was recrystallized from to afford methyl as powdery infrared 1715 nmr delta Methyl was dissolved in DMF and potassium carbonate was added in one Benzyl bromide in DMF was added dropwise to this with at room After eighteen hours the mixture was poured into water and extracted with ether x The extracts were washed with water x and brine dried and filtered through silica gel Merck then concentrated under reduced pressure to afford a yellow Distillation at 160eC and mmHg afforded methyl as a colourless oil infrared 1730 nmr delta A mixture of methyl and methyl formate in dry DMF was added dropwise to a stirred suspension of sodium hydride in in DMF at After stirring at 0eC for two hours the mixture was poured into water and washed with ether x The aqueous layer was acidified to pH4 with 6M hydrochloric acid then extracted with ether x The extracts and potassium carbonate mm were stirred together in DMF at room temperature under an atmosphere of After 18 the reaction mixture was poured into water and then extracted twice with The combined ether layers were washed twice with water and and then The resultant solution was filtered through a plug of silica gel and then concentrated to afford a pink afforded as a yellow gum which crystallised on AS Table EXAMPLE This Example illustrates the preparation of 61 of Table and potassium carbonate were stirred together in DMF at room After 2 hours the reaction mixture was poured into water and extracted twice with The combined ether layers were washed with water and brine and then Filtration and evaporation of the solvent under reduced pressure afforded a clear Chromatography gave as an oil which crystallised on trituration with NMR delta 3 60 afford crude methyl acrylate as a yellow infrared 1660 The crude methyl acrylate was dissolved in dry DMF and potassium carbonate was added in one Dimethyl sulphate in dry DMF was then added dropwise with After ninety water was added and the solution was extracted with ether x After washing with water x and the extracts were dried and concentrated under reduced and the resulting yellow oil solidified on trituration with Recrystallization from dry methanol afforded as a crystalline solid yield from methyl infrared 1640 nrar delta was dissolved in ethyl acetate and palladium on carbon was The stirred mixture was hydrogenated at three atmospheres with until no more hydrogen was taken then filtered through celite and silica gel Merck Concentration of the filtrate under reduced pressure afforded as a white crystalline solid infrared 1670 NMR delta insufficientOCRQuality

Claims (1)

1. A compound of the formula and stereoisomers wherein M is the residue of an inorganic A is either an oxygen atom or wherein n is 1 or Y and which are the same or are hydrogen or halogen or alkyl phenyl are hydrogen or g phenyl any of the foregoing alkyl moieties may be optionally substituted with phenoxy or carboxyl any ofthe foregoing alkenyl moieties may be optionally substituted by any of the foregoing phenyl moieties may be optionally substituted with one or more of or and and are independently phenyl or the phenyl and benzyl being optionally subsituted with alkyl or A according to claim vherein Y and vhich are same or are chlorine or bronine or C2 or or vherein the alkyl of any of the foregoing are optionally subs vith one or more alkoxy chlorine or bronine hydroxy or carboxyl and vherein the phenyl soieties of any of the foregoing are optionally substituted vith or more chlorine or bronine hydroxy or carboxyl and R and vhich are the sace or are A compound according claim 2 wherein A is an oxygen A compound according to one of claims 2 or 3 wherein and R2 are both A compound according to wherein A is an oxygen z are all and and R2 are both A compound according to any one of claims 2 to 5 wherein is an alkali metal 44 A compound according to 6 wherein is potassium salt of methoxyacrylate the AGENT FOR THE APPLICANT insufficientOCRQuality