Patent GB-882401-A (GB)
Title: Process for the manufacture of diphenyl ether derivatives
IPC: C07D263/42
Filed: 1958-08-21
Abstract: Compounds of the general formulae <FORM:0882401/IV (b)/1> <FORM:0882401/IV (b)/2> (wherein R12 and R3 each represent a hydrogen atom or a methyl group and R2 represents a hydrogen or iodine atom or a methyl group) are manufactured by heating an oxazolone derivative of the general formula <FORM:0882401/IV (b)/3> (wherein R4 represents a methyl or phenyl group) with a mixture of strong acetic acid and concentrated hydrohalic acid to form a pyruvic acid derivative of the general formula <FORM:0882401/IV (b)/4> decomposing this with hydrogen peroxide in alkaline solution to form an acetic acid derivative of the general formula <FORM:0882401/IV (b)/5> reducing the nitro group, and exchanging the amino group for an iodine atom via the diazonium compound to form the compound of formula (I), and, if desired, treating this with a mixture of strong acetic and hydrogen iodide to form a compound of formula (II) in which R2 represents a hydrogen atom or a methyl group, and further, if desired, when R2 is hydrogen, introducing a further iodine atom in the 31-position by the action of an aqueous alkaline solution of potassium iodide and iodine.  Alternatively the compound of formula (III) is converted by the action of sodium methoxide in the presence of methanol into a cinnamic ester derivative of the general formula <FORM:0882401/IV (b)/6> and this is isolated and heated with a mixture of strong acetic acid and hydrohalic acid to form the compound of formula (IV) which is further treated as above.  The compounds of formula (II) are also made by preparing the compound of formula (V) as above, treating it with a mixture of concentrated hydriodic acid, strong acetic acid and red phosphorus to form a compound of the general formula <FORM:0882401/IV (b)/7> diazotizing this and exchanging the diazonium group for iodine by the action of iodine and potassium iodide to obtain the compound of formula (II) in which R2 represents a hydrogen atom or a methyl group, and, if desired, introducing a third iodine atom as before; or by converting a cinnamic ester derivative of the general formula <FORM:0882401/IV (b)/8> by acid or alkaline hydrolysis into a pyruvic acid derivativ of the general formula <FORM:0882401/IV (b)/9> and treating this with hydrogen peroxide in an alkaline solution to form the compound of formula (I), which is further subjected to the steps set out as optional above.  The products and their salts are useful as medicaments (see Group VI).  211 - Methyl - 411 - [4 - (41 - methoxy - 31 - methyl- and - 31, 51 - dimethyl - phenoxy - 3 - iodo-5-nitrobenzylidene]-oxazolone-(511) are prepared by reacting 4-(41-methoxy-31-methyl- or 31,51 - dimethyl - phenoxy) - 3 - iodo, 5 - nitro benzaldehyde with aceturic acid, anhydrous sodium acetate and acetic anhydride.  4 - (41 - Methoxyphenoxy) - 31, 5 - di-iodo - a  - benzoylaminocinnamic acid methyl ester is prepared from the corresponding 3-iodo-5-nitro compound by reducing the nitro group and replacing the resulting amino group by iodine via the diazonium compound.ALSO:As medicaments, e.g. as hypocholesterolaemic agents in geriatrics, may be employed compounds of the general formulae <FORM:0882401/VI/1> or their salts, wherein R12 and R3 each represent a hydrogen atom or a methyl group and R2 represents a hydrogen or iodine atom or a methyl group.  They may be presented in the form of tablets, dragees, capsules, suppositories or ampoules.