Slotta, K. H. published the artcile¦Â-Phenylethylamines. I. Mescaline and mescaline-like substances, Name: (E)-3-(2,4-Dimethoxyphenyl)acrylic acid, the publication is Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen (1930), 3029-44, database is CAplus.
In addition to the sympathomimetic action which is a general property of ¦Â-aryl-ethylamines and -ethanolamines, mescaline, 3,4,5-(MeO)3C6H2CH2CH2NH2 (I), possesses a peculiar narcotic action. For a pharmacol. and clinical investigation of I and a study of its relationships to other sympathomimetic drugs it was necessary to find a way by which it would be possible to prepare several hundred g. of I. The only method by which it had hitherto been synthesized (RCHO (+ MeNO2) ¡ú RCH:CHNO2 (+ H2) ¡ú RCH2CH:NOH (+ H2) ¡ú RCH2CH2NH2) serves to establish its structure rather than to prepare the compound The new method should also make it possible to prepare more easily the isomers of I, as well as mono- and dimethoxyphenylethylamines, in order to determine the influence of the position and number of the MeO groups on the physiol. action of the alkoxyphenylethylamines. An examination of 4 other possible methods of preparation indicated that the only feasible one was that based on the scheme RCHO (+ CH2(CO2H)2) ¡ú RCH:CHCO2H (+ H2) ¡ú RCH2CH2CO2H (+ SOCl2) ¡ú RCH2CH2COCl (+ NH3) ¡ú RCH2CH2CONH2 (+ KOBr) ¡ú RCH2CH2NH2. The m- and p-mono- and the 2,3-, 3,4-and 3,5-di-MeO compounds have already been prepared by this method but in all attempts to prepare I it had hitherto been impossible to carry out the last step. S. and H. have now found, however, that under certain conditions not only I but also its isomers can readily be obtained in very satisfactory yield by using concentrated NaOBr for the Hofmann degradation. The condensation of the aldehydes with CH2(CO2H)2 was effected in 2-3 parts C5H5N (distilled over KOH) and 1-5 cc. piperidine per mol. of aldehyde; com. CH2(CO2H)2 can be used directly and a 20% excess. is quite sufficient. The splitting off of CO2 from the primary di-CO2H acid is almost quant. on the H2O bath and only in a few cases was it necessary to boil the C5H5N solution a short while. The yield of RCH:CHCO2H was in general above 80%. The reduction of the unsaturated acid was in all cases easily carried out with an excess of Na-Hg, usually on the H2O bath; a higher temperature was required only where the unsaturated acid was difficultly soluble in NaOH, and a toning down of the alkalinity with AcOH was necessary only with 3,4,5-(MeO)3C6H2CH:CHCO2H. The chlorides RCH2CH2COCl were obtained by heating the acids in CHCl3 4-5 hrs. on the H2O bath with twice the calculated amount of SOCl2; they were not isolated but the reaction mixtures were concentrated to about 0.5 volume in vacuo and added, with cooling, to concentrated NH4OH containing about 10% NaOH (only 2,4-(MeO)2C6H3CH2CH2CONH2 could not be obtained in this way). For the successful degradation of the amides to the amines, it is necessary to have a very pure amide. The statement in the literature that NaOCl gives better yields than NaOBr was confirmed for only some of the amides (the best results were obtained with a solution prepared by passing 5.5 g. Cl into 10 g. NaOH in 100 cc. H2O). The behavior of the amides in the Hofmann degradation depends greatly on the position and nature of the nucleus substituents. The products are best worked up by distillation in vacuo. The physiol. action of the amines prepared will be described later by Hesse and Lange. o-MeOC6H4CH:CHCO2H, m. 183¡ã (80% from o-MeOC6H4CHO), gave 99% MeOC6H4CH2CO2H, m. 92¡ã (literature, 85-6¡ã); the amide, m. 111¡ã (86.3% yield), gave with NaOCl 35.2% o-MeOC6H4CH2CH2NH2, b. 115-20¡ã in the vacuum of a H2O pump (HCl salt, m. 143¡ã; sulfate, m. 230¡ã). m-HOC6H4CHO, m. 106¡ã (69% by diazotization of m-H2NC6H4CHO, prepared from the NO2 compound with FeSO4), yielded 80% of the MeOC6H4CHO which gave 69% MeOC6H4CH: CHCO2H, m. 177¡ã; the saturated acid, m. 50¡ã (80% yield) gave 27.5% of the amide, b12 222-5¡ã, m. 56¡ã, which yielded with NaOBr 61% (with NaOCl 19%) of m-MeOC6H4CH2CH2NH2, b12 128¡ã. p-MeOC6H4CH2CH2NH2. HCl, m. 210¡ã, was obtained in 43% yield with NaOCl from the amide which itself was obtained in 75% yield through the MeOC6H4CH:CHCO2H (92.5%) and the saturated acid (81%). p-iso-PrC6H4CH:CHCO2H, m. 165¡ã (64%); saturated acid, m. 73¡ã (98%); amide, m. 142¡ã (81.5%), boils explosively with NaOCl at 80¡ã and at 65¡ã gives only a little a ¦Â-(p-isopropylphenyl)ethylamine, b. 150¡ã in the vacuum of a H2O pump (HCl salt, m. 270¡ã). Vanillin Et ether, m. 63¡ã (85% from vanillin and alk. Et2SO4), gave 89% 3-methoxy-4-ethoxycinnamic acid, m. 205¡ã; propionic acid, m. 130¡ã (79%); amide, m. 124¡ã (33.9%), gave with NaOCl the ethylamine, b15-8 165¡ã (HCl salt, m. 120¡ã). m-C6H4(OMe)2, b12: 117-8¡ã (90% from m-C6H4(OH)2 with alk. Me2SO4), gave in Et2O with HCN, HCl and ZnCl2: 76% of 2,4-(MeO)2C6H3CHO; 2,4-(MeO)2C6H3CH:CHCO2H, m. 138¡ã (99%); propionic acid, m. 105¡ã (94%); attempts to prepare the amide through the chloride gave a red-brown oil which decomposed on distillation, in vacuo. 3,4-CH2O2C6H3CH:CHCO2H, m. 232¡ã (94%); propionic acid (92%); amide (83.5%), gave with NaOCl 37% of the ethylamine-HCl, m. 206¡ã, 1,2,3-C6H3(OMe)3, b12 140¡ã (65% with alk. Me2SO4), gives with HCN and AlCl3 in C6H6 53% 2,3,4-(MeO)3C6H2CHO, b12 170¡ã. 2,3,4-Trimethoxycinnamic acid, m. 172¡ã (94%); propionic acid, m. 76¡ã (65%); amide, m. 171¡ã (63.5%), gives with NaOBr 71.5% ¦Â-(2,3,4-trimethoxyphenyl)ethylamine, b12 167¡ã, quickly forms the carbonate in the air. 3,4,5-(MeO)3C6H2CO2H (86% from (HO)3C6H2CO2H with alk. Me2SO4); chloride (86% with PCl5) in boiling xylene (distilled from Na) with Pd-BaSO4 and H gave in 30 hrs. 80% 3,4,5-(MeO)3C6H2-CHO, m. 74¡ã; cinnamic acid, m. 124¡ã (80%); ¦Â-(3,4,5-trimethoxyphenyl) propionic acid, m. 98¡ã (88% yield); amide, m. 106¡ã (60%), gave with NaOBr (52g. Br and 150g. NaOH in 375 cc. H2O) 66% I, b12, 180¡ã (HCl salt, m. 181¡ã). p-BrC6H4OMe, b12 120¡ã (82.9% from PhOMe in AcOH with Br vapors) gave in Et2O with Mg (activated with I) and ethylene oxide and subsequent decomposition with HCl 31.1% of p-MeOC6H4CH2-CH2OH, b. 145-60¡ã in the vacuum of the H2O pump, and this with boiling 47.5% HBr yielded 45% of the bromide, b12.6 140-50¡ã, from which, when refluxed with a mixture of C6H4(CO)2NH and 0.5 mol. K2CO3 until no liquid condensed in the condenser tube, then treated in alc. with N2H4.H2O and finally with HCl gas, was obtained 11.8% p-MeOC6H4CH2CH2NH2.HCl, m. 211¡ã. 4-Bromoveratrole, p-BrC6H4OH, p-BrC6-H4OAc, o- and p-BrC6H4NO2 and o-C6H4Cl2 could not be made to react with Mg in either Et2O, (iso-Am)2O or otherwise.
Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen published new progress about 16909-09-4. 16909-09-4 belongs to catalysis-chemistry, auxiliary class Alkenyl,Carboxylic acid,Benzene,Ether, name is (E)-3-(2,4-Dimethoxyphenyl)acrylic acid, and the molecular formula is C7H13NO2, Name: (E)-3-(2,4-Dimethoxyphenyl)acrylic acid.
Referemce:
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Catalysis – Wikipedia