ACTION OF SODIUM AMAI,CIARI ON hIETHYLENE ETHERS. 2413CCXLVII. - Action of Sodium Amalyam on Meth ylerieEtlzei-s.By ARTHUR HENRY SALWAY.IN the course of the author’s previous investigations, which ledt o the synthesis of cotarnine (Trans., 1909, 95, 1204; this vol.,1208), the reduction of 3-methoxy-4 : 5-methylenedioxycinnamicacid (I) was described. In this reaction it was observed that thonormal reductdon product, namely, P-3-methoxy-4 : 5-methylene-dioxyphenylpropionic acid (11), was invariahly accompanied by aconsiderable proportion of a by-product. This substance, of whic2414 SALWAY: ACTION OF SODIUMno account was given in the previous communications, has now beenisolated in sufficient quantity to render its complete examinationpossible.The purified compound was found to possess the propertlies of aphenol and of a carboxylic acid, and gave analyses correspondingwith the empirical formula C,,H,204.It is evident that the p r eduction of such a compound from 3-methoxy-4 : 5-methylenedioxy-cinnamic acid (I) can only be explained by the simultaneousreduction of the aliphatic side-chain and the substitution of ahydroxyl group for the methylenedioxy-complex. The constitutionof the resulting compound would therefore appear to be representedby one of the two formulz A and B :OM0(1.)/\CH~-CH,-CO,Hor HO\/ I IOMe(B.)I n order to decide between these formulq the substance wasconverted by means of methyl sulphate into a dimethoxyphenyl-propionic acid, which melted at 61-62O. The dimethoxy-acidcorresponding with B, namely, P-3 : 4-dimethoxyphenylpropionicacid, melts, according to Tiemann and Nagai (Ber., 1878, 11, 653),at 97O, whilst the 3 : 5-dimethoxy-acid corresponding with A doesnot appear to have been hitherto described.Formula B is thusshown to be inadmissible, and consequently A most probably repre-sents the constitution of the substance under examination. Positiveevidence in support of this conclusion wits obtained by convertingthe dimethoxypropionic acid into the corresponding dimethoxy-benzoic acid by oxidation with alkaline permanganate solution.The product of oxidation melted at 180-181°, and was found tobe identical with 3 : 5-dimethoxybenzoic acid. It is thus shownthat in the reduction of 3-methoxy-4 : 5-methylenedioxycinnamicacid (I), the normal reaction is accompanied by a secondary changeinvolving the disruption of the methylenedioxy-complex and theformation of P-5-hydroxy-3-methoxyphenylpropionic acid (111),according to the scheme on p.2415.It was next deemed of interest to ascertain whether othermethylene ethers are capable of undergoing a similar change, andaccordingly piperonylacrylic acid (IV) was subjected to the actionof sodium amalgam. In this case, also, it was found that reductioAMALGAM ON METIIYLENE ETHERS. 2415takes place with partial conversion of the methylenedioxy-complexinto a hydroxyl group, the products of the reaction being a qixture(11.)HO/\CH,*CH,~CO,Hand 0 OMe(111.)of p-3 : 4-methylenedioxyphenylpropionic acid (V) and P-3-hydroxy-phenylpropionic acid (VI) :A similar react-Jn has been observed by Ciamician and Silber(Ber., 1890, 23, 11621, who have shown that kosafrole (VII), whenreduced by sodium and alcohol, is converted into a mixture of3 : 4-methylenedioxypropylbenzene (VIII) and m-propylphenol(IX), whilst Thorns ( B e y ., 1903, 36, 3449) records the fact thatisomyristicin (X), under similar conditions, yields both 5-methoxy-3 : 4-methylenedioxypropylbenzene (XI) and 5-methoxy-3-propyl-phenol (XII) :O/\CH:CHM~ --3 CH2< I O/\CH,*CH,Me I(VIII. )O\/CH,< I IO\/(VII.)and HO()CH,*CH,M~o/’\cH,~cH,M~O\/I OACH:CHM~ --3 CH,< 1 CH,< I IO\/OMe OMe(XI. 1HO()CH2*CH2Me\/ andOMe(XII.2416 SALWAY: ACTION OF SODIUMIt is worthy of note that in each of the above examples of thedisplacement of a methylenedioxy-complex by a hydroxyl group,the latter appears in the meta-position with regard to the side-chain.Moreover, the position of the unsaturated linking in theside-chain is of importance in determining the course of the reaction,since only those compounds which contain the unsaturated linkingin the aP-position with regard to the benzene nucleus appear tobe capable of undergoing the above-described transformation. Thus,for example, the methylenedioxy-group of isomyristicin (X) is readilydecomposed by means of sodiam and alcohol, whilst myristicin, inwhich the unsaturated linking is in the By-position, does not sufferthis change.EXPERIMENTAL.Reduction of 3-Met7hoxy-4 : 5-m~ethylened~oxycinlzamic ,4 cid(I, p.2415).A solution of one part of 3-methoxy-4 : 5-methylenedioxycinnamicacid in 20 parts of 1 per cent. aqueous sodium hydroxide wasreduced by the gradual addition, with constant stirring, of 16 partsof sodium amalgam (4 per cent.). After the amalgam had beencompletely decomposed, the mixture was acidified, the precipitatedoil extracteg with ether, and the ethereal solution washed, dried,snd the solvent removed. I n this manner the product of reductionwas obtained as a light brown oil, which gradually became crys-talline. A preliminary examination of the product indicated thepresence of a considerable proportion of a phenolic carboxylic acidin addition to the normal reduction product, B-3-methoxy-4 : 5-methylenedioxyphenylpropionic acid.I n order to effect aseparation of these compounds, the mixtnre was dissolved in alcoholand esterified by means of dry hydrogen chloride, after which theexcess of alcohol was removed and the esters extracted with ether.The ethereal solution was first washed with aqueous sodiumcarbonate to remove any unesterified acid, and then shaken withdilute sodium hydroxide. The sodium hydroxide extract, whichcontained the phenolic ester, was warmed for a short time tocomplete the hydrolysis of the latter, then acidified and extractedwith ether. This ethereal extract yielded a colourless solid, whichwas recryst.allised from hot water, when it separated in fiat,hexagonal plates, melting at 1 2 7 O :0.1103 gave 0.2482 CO, and 0.0635 H,O.0.2800 required for neutralisation 14.35 C.C.N / 10-KOH.C = 61.4 ; H = 6.4.M.W. = 195.C,,HI2O4 requires C = 61.2 ; H = 6.1 per cent. M.W. = 196AMALGAM ON METHYLENE ETHERS. 2417As already explained in the introduction, this substance was foundto be B-5-hydroxy-3-methoxyphenylpropionic acid.(3-5-Hydroxy-3-methoxypl~enylpro~onic acid (111, p. 2415) isreadily soluble in ether, alcohol, or hot water, and crystallises fromthe latter in colourless, hexagonal plates, which gradually becomepink on exposure to air. It is insoluble in benzene or lightpetroleum. Its amide, MeO*G,H,(OH)*C'H,*CHz*CO*NH2, crys-tallises from water in prismatic needles, melting at 126O.I n order to prepare the methyl derivative of the above compound,10 grams of the phenolic acid were dissolved in methyl alcohol and5 C.C.of methyl sulphate, and 10 C.C. of a 50 per cent. solution ofpotassium hydroxide added. After the vigorous reaction hadsubsided, the same quantities of methyl sulphate and alkali wereagain added, and the mixture heated for a short time on the water-bath. The alkaline liquid was then acidified and extracted withether, when the ethereal extract yielded an oil which graduallysolidified. This product was purified by crystallisation from amixture of benzene and light petroleum, from which it separatedin clusters of colourless, silky needles, melting at 61-62O :0.1076 gave 0-2490 CO, and 0.0649 H,O.0.4465 required for neutralisation 21.25 c.c: A'/ 10-NaOH.C=63*1; H=6.7.M.W.=210,C,,H,,04 requires C = 62.9 ; H = 6.7 per cent. M.W. = 210.p-3 ; 5-Dim e t hoxy ph en ylpro pionic acid,C,H,(MeO),*CH2*CHz-C0,H,is readily soluble in the usual organic solvents, excepting lightpetroleum. It yields an amide, which crystallises from a mixtureof benzene and petroleum in colourless needles, melting at 80-81O.The position of the methoxy-groups in the above compound wasascertained by oxidising it quantity of the substance with a, hotalkaline solution of potassium permanganate. A t the end of theoxidation, the liquid was cooled, an excess of sulphur dioxide added,and the precipitated oxidation product collected. It was re-crystallised from hot water, when it separated in thin needles,melting at 180-181O.(0.2045 required for neutralisation 11.25C.C. N/10-NaOH. M.W. = 182. Calc., M.W. = 182.)This substance possessed all the properties of 3: 5-dimethoxy-benzoic acid (Bulow and Riess, Ber., 1902, 35, 3901), and wasevidently identical with that compound.Reduction of Piperonylacrylic Acid.The reduction of piperonylacrylic acid by means of sodiumamalgam was first described by Lorenz (Ber., 1880, 13, 758), whoisoIated piperanylpropionic acid from the product of the reaction2418 CAMPBELL AND THORPE : AN IKSTANCE ILLUSTRATINGbut did not record the formation of a phenolic compound. Inview, however, of the results obtained in the above reduction of3-methoxy-4 : 5-met5h-ylenedioxycinnamic acid, it seemed probablethat some P-5-hydroxyphenylpropionic acid would be formed in thoreduction of piperonylacrylic acid.I n order to ascertain if thiswere the case, 20 grams of piperonylacrylic acid were reduced withsodium amalgam in the manner described in connexion with thereduction of 3-methouy-4 : 5-methylenedioxycinnamic acid. Theproduct was then esterified, and, by means of dilute sodiumhydroxide, separated into a non-phenolic and a phenolic ester. Theformer amounted to 18 to 19 grams, and yielded on hydrolysispiperonylpropionic acid, melting at 8 5 O , whilst the latter, whenhydrolysed, yielded a brown oil (2 grams), which gradually solidifiedon agitation with benzene. This substance was purified by re-crystallisation from a mixture of ether and benzene, and was thusobtained in colourless needles, melting at 1 1 0 O . (0.1922 required11.8 C.C. X/lO-NaOH for neutralisation. M.W. = 163. Calc.,M.W. = 166.)This compound possessed all the properties of 3-hydroxyphenyl-propionic acid, and was evidently identical with it (Braunstein,Ber., 1882, 15, 2050).The action of sodium amalgam on piperonylacrylic acid istherefore analogous to that which takes place when 3-methoxy-4 : 5-methylenedioxycinnamic acid is reduced. The yield of phenolicacid in the latter case is, however, much greater than in the former.THE WELLCOME CHEMICAL RESEARCH LABORATOKIES,LONDON, E.C