Studien über Morphin

Abstract

203sch6n krystallisirende Cldorid CJf&lS. COCl iiberfuhrt, letzteres unter sdiwacher Erhitzong in eiuem Iicihleiidioxydstrum vom phaspliorouyrlilorid niiigliclist befreit, tlns Clilorid dann mit Anilin mischt wid erwdrmt, ~i l Y d U f die su gebildete erkaltete feste Masse zerreibl, erst rnit SnlzsBure , tiierauf mil Sodaliisiing wksclit, daitn nus Alkoliol unil darnuf ails Benzol urnltrystallisirt. Dies Anilid is1 unliislich in Wasser, Iijslich in Alkohol, Eiscssig u i i d Benzol. Aus t3enAol krystallisirt es in sehr schiinan grorsen, mcist ( W a s bri4unlichen hismen, die bei 2400 c. schmelxen. 0,2264 g dcs liifttrockHutln hni!ids gaben 11,s cbcm N h i 20' c. und 740 nun U. Bcrechnct Crcftmdnn N 5,3 5,s. Stridieii uber Rrlorphin : v m 0. Hesse. (Einl;elaufen den 5. October 1883.) Bekanntlich wtolltc in neucrer Zcit P o 1 s t o r f f "j gefunden haben, dds das hlorphin bei Bellandlung mil Benzoylchloriir Tritienzo3-linoryhin bililt: untl soniit drei H)-droxyle enthalte. Indefs wiesm W r i g h t und H e 11 n i e ++*I bald darauf nach, defs das als Tril~enzoyltnor.~,ttiit anges;)rochent! ,I;lorpliindcrivai vdlig iibt!rt~iiistiiiimr niit den1 frijhcr von B e c k t: t t und W r i g h t 4*3.:) dmch Einwirkunp ron 1Rt?iizo~saurcanhycIrid auf Blorpltin erhaIt~~ttt:it DibelleoyIrnclrptiin, sodds hiernach das Alkaloid nur zwci I lydi*oxyle t!l>tl\itltc~l wiirde. __ .--* ) Rcr. d. deutsch. cliern. Gos. IS, 98. *') Joiim. of the Chom. SOC. 121 32, GOO. ljaselbst [z] lS, 23.zb4 H e~s e , StudienObwohl iiiin heute die beziigliche Frnge als gel& zu betrachten ist, nuchdem v. G e r i c 11 t e n *) das dritte im Morphin enthaltene At.orri Sauerstoff als ,,BruckensauerstoP erkannte, so war eben dies, als ich vor drei Jahren nicine Untcrsuchung dber Mnrpliin heyann, nocli nic'lrt dcr Ftdl ; jedoch hoIRe ich dieses Ziel dadurch zii crrcichen, dafs ich das Morphin fort und fort in neiier Form mil Saurrurihydriden in Reaction treten lassen wiirdc.Xu tliescin Zwcck habe icti zirnlchst auf Morpliin Essigsaiirtxrihydrid wid vcrgleichshaibw rroyions8ar~Hnhydrid einwirken bssen urid alsdann diese Procedur init Methylderiveten desselben vorgenonirnen, die in irgend h e r unkn ndier bezeichneteri Weise dargestellt worden waren und aiicli unten niher bescbrieben werdcii. M'ahrend ich inicd rnit dieser Untersuchurig bescliaftigte , sind ZIWP diese nielhylirten Morphine zum Tlieil voii C, r i m t~ u x **) beschrieben worden; allein der Vollstiindiglieit dieser Mittheilung lialher werdt: iclr auf meine Itctreffciiden Vwsuclie zuriickkominen iriussen, ganz alrgesrhcti ditvon, tlafs dieselben wolil ziiin Tlicil friiher ausgefuhrt sirid als jciie G r i ma ti x' urid inir in tlieser Beziehung ein gewisses Vorrecht zukoinmen wurdr.Revor ich i n d c t suf diese Mittheiliing iibergehe, mitchte icli drrselben einige Worte uirer die Hezeiclirtung der in den Bereicli dieser Mittheilung gehiirigen StcfTc voraiisschicken.Bekannllich wird uriter Acctylniorphin Morphin verslariden, in welclletii IIydroxylwrtsserstoff tliirch Acctyl siihslil.uirt ist. Je n a...

Heteroatom Analogues of Hydrocodone: Synthesis and Biological Activity

“…10 Of particular interest was the application of Hofmann’s elimination procedure to codeine by von Gerichten 11 and Knorr, 12 with subsequent refinements by Hesse 13 in the 1880s. We envisioned transforming hydrocodone to a key aldehyde intermediate by Hofmann elimination and subsequent Polonovksi reaction 14 of an N -oxide derived from an N,N -dimethyl amine, such as 19 , Scheme 1.…”

“…The synthesis of compounds of type 15 and 16 was envisaged to originate from a common intermediate made available by methods employed in the well-known degradation studies that led to the final structure elucidation of morphine after nearly 120 years of effort . Of particular interest was the application of Hofmann’s elimination procedure to codeine by von Gerichten and Knorr, with subsequent refinements by Hesse in the 1880s. We envisioned transforming hydrocodone to a key aldehyde intermediate ( 21 or 26 ) by Hofmann elimination, with a subsequent Polonovksi reaction of the N -oxide derived from the resulting N , N -dimethyl amine 19 , or its protected form 24 , Scheme .…”

“…The following abbreviations were used to explain multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad, dd = doublet of doublets, dt = doublet of triplets, ddt = doublet of doublet of triplets. 13 C NMR spectra were recorded at 75 MHz or at 151 MHz and are reported in terms of chemical shift. All chemical shifts were calibrated using residual nondeuterated solvent as an internal reference and are reported in parts per million relative to trimethylsilane.…”

“…They prepared and tested both axial and equatorial derivatives of sulforphanol (13) and sulfallorphan (14), finding that the sulfonium analogues retained potency. Furthermore, the agonist versus antagonist activity associated with these compounds was found to depend on the conformation of the S-substituent in agreement with Snyder's proposal (equatorial allyl group confers antagonist activity, axial methyl confers agonist activity).…”

DARK Classics in Chemical Neuroscience: Opium, a Historical Perspective

“…The structure elucidations of morphine and codeine are intertwined because codeine is just the methyl ether of morphine. Two researchers, Grimaux and Hesse, both independently figured out that they could produce codeine from morphine with methyl iodide under basic conditions in 1881 and 1884, respectively. − Grimaux was also able to draw comparisons between phenol and its methyl ether with morphine and codeine.…”