Michael-Additionen mit N-Acylaminosäureestern, 4. Mitt. Einstufensynthese von 1-Aryl-pyrrolizidin-3,5,7-trionen

Michael Additions with Esters of Acylamino Acids, IV: One-Step-Syntheses of 1-Arylpyrrolizidine-3,5,7-triones Michael additions between N-acylglycine ester and α,β-disubstituted ethyl acrylates yield stereoselectively, 1,8H-trans-1-arylpyrrolizidine-3,5,7-triones in a one-step reaction.     

Michael-Additionen mit Acylaminosäureestern, 7. Mitt. Trans-3-Aryl-2-hydroxymethyl-pyrrolidone-5 als Synthone für azaanaloge Pharmaka

Michael Additions with Acylamino Acid Esters, VII: Trans-3-Aryl-2-(hydroxymethyl)-5-pyrrolidones as Synthons for Aza-Analogous Drugs Cyclizing Michael addition of aryl acrylates to N-acetylamino acid esters yields stereoselectively new trans-3-aryl-5-oxopyrrolidine-2-carboxylic acids 4 . Esters of 4 are reduced with NaBH₄ to yield the trans-3-aryl-2-(hydroxymethyl)-5-pyrrolidones 6.     

Michael-Additionen mit Acylaminosäureestern, 6. Mitt. Substituenteneinfluß bei der Synthese von Pyrrolidon-5- bzw. Pyrrolidon-4-derivaten

Michael Additions with Acylamino Acid Esters, VI: The Influence of Substituents on the Synthesis of 4- and 5-Pyrrolidones Acylamino acid esters react with substituted ethyl acrylates to yield pyrrolidones. Depending on the nature of the substituents α-pyrrolidones 3 or β-pyrrolidones 4 are formed. The influence of the substituents on the course of these Michael additions has been studied.     

Michael-Additionen mit Acylaminosäureestern Die stereoselektive Synthese von 2-cis-Alkyl-2-trans-äthoxycarbonyl-3-pyridyl-(3) (r)-pyrrolidonen-5

Michael Additions with Acylamino Acid Esters In aprotic solvents the sodium salts of simple N-acylamino acid ethyl esters react with ethyl-3-pyridyl-(3)-acrylate in a stereoselective Michael reaction by formation of C-C-bond to give 2-cis-alkyl-2-trans-ethoxycarbonyl-3-pyridyl-(3) (r)-pyrrolidones-5 (5) . Only with N-ethoxycarbonylglycine ethyl ester derivatives of pyrrolidones-4, 3 are obtained by the expected C-N-addition described by Kuhn²⁾.     

Michael-Additionen mit Acylaminosäureestern, 2. Mitt. Darstellung von 3-Aryl-2,4-bis(äthoxycarbonyl)-2-methyl-pyrrolidonen-(5)

Michael Addition with Acylamino Acid Esters II. – Preparation of 3-Aryl-2,4-bis(ethoxycarbonyl)-2-methyl-5-pyrrolidones Michael addition of DL-acetylalanineethyl ester with diethyl arylidenemalonate yields a mixture of the 3-aryl-2,4-bis(ethoxycarbonyl)-2-methyl-5-pyrrolidones 3 and 4 . In contrast to analogous reactions this synthesis is not stereoselective.     

Dihydroisochinolinumlagerung, 37. Mitt. Synthese von Isochinoliniumsalzen mit sperrigen C-1-Substituenten als Vorstufen für 1,2-Dihydroisochinoline

Rearrangement of Dihydroisoquinolines, XXXVII: Syntheses of Isoquinolinium Salts with Bulky C-1-Substituents as Precursors of 1,2-Dihydroisoquinolines The Reissert compound 1 is alkylated to give the compounds 2a-2d . From these by saponification the isoquinolines 3a-3d are obtained which are reacted with methyl iodide to yield the iminium iodides 4a-4d.     

Dansylchlorid als Reagens für Sympathicomimetika, 2. Mitt. Fluorimetrische Gehaltsbestimmung von Ephedrinhydrochlorid als Dansylderivat in Tabletten

Dansyl Chloride as a Reagent for Sympathomimetic Amines, II: Fluorimetric Determination of Ephedrine Hydrochloride as its Dansyl Derivative in Tablets A fluorimetric method has been developed for the determination of ephedrine hydrochloride as its dansyl derivative in ephedrine tablets. After “dansylation” the dansyl derivative is separated by thin-layer chromatography and eluted from the plate with ethanol. The dansyl derivative content of these solutions is determined. Ephedrine hydrochloride was determined from tablets and from tablet powder. The precision and recovery studies show the method to be very reliable with low values for the relative standard deviation.     

Liposomen als Wirkstoffträger für Chinaalkaloide und Modell für Wechselwirkungen von Chinaalkaloiden mit Erythrocyten

Liposomes as Drug Carrier for Cinchona Alkaloids and as a Model for the Interaction of Cinchona Alkaloids with the Red Blood Cell Encapsulation studies in negatively charged liposomes reveal high membrane binding rates for the cinchona alcaloids. The binding is based on electrostatic interactions between the negatively charged lipid headgroups and the cinchona alcaloid molecules, which have cationic character. Neutral and positively charged membranes composed of unsaturated lipids virtually appear to be no barriers for the diffusion of these substances. Binding studies of quinine to Red Blood Cells (RBC) reveal, that the asymmetric structural principle of the RBC-membrane plays an important role for the uptake of the blood schizontoidal drugs into their domains.     

Thion- und Dithioester, 41. Mitt. Zur Reaktion von Dithionmalonsäureestern mit Elektrophilen

Thiono and Dithio Esters, 41. - Reaction of Dithiono Malonic Esters with Electrophiles Dithiono malonic esters 1 react with alkali alkoxides to form the stable alkali salts 2 . According to an X-ray analysis for the N,N,N′,N′-tetramethylformamidinium salt 18 their anions adopt a trans,s-trans configuration in the crystalline state. By NOE experiments the same configuration is confirmed for solutions ([D₆]DMSO or D₂O). Alkylation of 2 , however, gives rise to the Z-configurated thiono acrylic esters 4 , By oxidation of 1a with tert.-butyl hypochlorite or iodine the 1,2-dithiolium salts 5 and 7 were obtained. The reaction of 1a with N,N-dimethylformamide diethylacetal ( 8 ) in ethanol leads to the formation of the dimethylaminomethylene compound 12 , in ether the formamidinium salt 18 precipitates. The latter decomposes to N,N-dimethyl thioformamide 20 and the thiono acrylic ester 21 .     

Zur Synthese von Diaza-bicyclo-nonan-dicarbonsäureestern

Synthesis of Diaza-bicyclo-nonane-dicarboxylates A three-step synthesis and a one-step synthesis of 3 are described and compared, starting with acetonedicarboxylates. In the three-step synthesis 2 can be transformed directly into 3 without prior cleavage of the ring. The yield of the one-step synthesis depends very strongly on the nature of the ester group of the acetonedicarboxylate.     

Zur Synthese des Phaeantharins, 1. Mitt. Syntheseplan für Phaeantharin und Synthese des Bausteines A: 4′,5-Dibrommethyl-2-methoxydiphenylether

On the Synthesis of Phaeantharine, I: Plan of the Synthesis of Phaeantharine and Synthesis of the Unit A: 4′,5-Bis(bromomethyl)-2-methoxydiphenyl Ether A plan for the synthesis of phaeantharine is proposed. The 4′,5-bis(bromomethyl)-2-methoxydiphenyl ether (5) , required for this approach, was prepared in three steps from 4-bromobenzaldehyde (1) and 3-hydroxy-4-methoxybenzaldehyde (2) via the diformyldiphenyl ether 3 and the diol 4 with a total yield of 46%.     

LDA-Katalysierte Diastereoselektive Michael-Additionen Mit Glycinderivaten: Synthese von 4-Substituierten 3-Aryl-2-N(Diphenyl-Methylen)-glutaminsäureestern und Ihre Umwandlung in 4-Substituierte 3-Aryl-2-Ethoxycarbonyl-5-Oxo-Pyrrolidine

LDA-catalyzed Diastereoselectlve Michael -Additions with Glycine Derivatives: Synthesis of 4-Substituted 3-Aryl-N(diphenylmethylene)glutamates Followed by Cyclization to 4-Substituted 3-Aryl-2-ethoxycarbonyl-5-oxo-pyrrolidines Synthesis and stereochemistry of 4-substituted diethyl 3-aryl-N(diphenylme-thylene)glutamate 3 by LDA-catalyzed Michael addition of ethyl-N(diphe-nylmethylene)glycinate with diethylbenzylidene-malonate or ethyl-2-cyano-cinnamates, respectively, are reported. Deprotection yields diethyl-3-aryl-glutamates 4 which are easily cyclized to 4-substituted 3-aryl-2-ethoxycarbnyl-5-oxo-pyrrolidines 5.     

Eine neue Synthese für Arborin und strukturanaloge 4(1H)-Chinazolinone, 2. Mitt

A New Synthesis for Arborine and 4(1H)-Quinazolinones with Analogous Structures, 2. Acylaminals like 2,3-dihydro-1-methyl-4(1H)-quinazolinones, substituted in 2-position, were dehydrogenated to the title compounds with mercuric EDTA.     

Thion- und Dithioester, 40. Mitt. Zur Reaktion von Dithionmalonsäureestern mit nucleophilen Stickstoffbasen

Thiono and Dithio Esters, 40. - Reactions of Dithionomalonic Esters with Nucleophilic Nitrogen Bases Dithionomalonic esters 1 , obtained from malonitrile via malonodiimidium salts 5 by thiolysis, react with amines under elimination of H₂S to form the 3-amino-thioacrylic O-esters 11 . The alkali salts of 1 condense with amines to give the malonodithiomides 12 by loss of 2 molecules of alcohol. Oxidative cyclization of 11 leads to the isothiazoles 16–18 . Reation of 1 with hydrazines gives rise to the pyrazoles 20–22 ; with amidines the pyrimidines 23 and 24 were obtained.     

Synthese von Phosphorsäurephenylesterdiamiden, 1. Mitt.

Synthesis of Phenyl Phosphorodiamidates, I Two procedures are described for the synthesis of phenyl phosphorodiamidates in high yields. These compounds can be represented by the general formula 6 and are used for cyclisation reactions leading to phosphabarbituric acids.     

Synthesen mit Nitrilen, 71. Mitt. Zur Synthese von 4-Hydroxynicotinsäure aus Butadiendicarbonitrilen

Syntheses with Nitriles LXXI: Synthesis of 4-Hydroxynicotinic Acid from Butadienedicarbonitriles Condensation of 1,1-dicyano-2-ethoxy-1-propene (1) with dimethylformamide dimethylacetal leads to butadienedicarbonitriles 2 . Ring closure of 2 with hydrogen halides or ammonia yields 4-alkoxy-2-halo-(or 2-amino)pyridine-3-carbonitriles 3 or 5 . Catalytic reduction of 3 yields 4-alkoxypyridine-3-carbonitriles, which can be converted to 4-hydroxynicotinic acid (9) by treatment with conc. hydrochloric acid.     

Untersuchungen an 1, 4-Naphthochinonen, 17. Mitt.: Untersuchungen zur Synthese von 3-Hydroxyjuglonderivaten

1, 4-Naphthoquinones, XVII: Studies on the Synthesis of 3-Hydroxyjuglone Derivatives Contrary to 3-chlorojuglone ( 1 ) the isomeric 2-chloro derivative 2 is a suitable compound for the synthesis of 2-methoxy- [ 6 ] and 2-hydroxyjuglone in CH₃OH/OH. In DMSO-CH₃O^? the results are inverse but the yield (50%) of 3-methoxyjuglone ( 5 ) is only moderate. The best method for the preparation of this key compound is acid catalyzed addition of CH₃OH to juglone followed by Fe (III)-oxidation.     

Heterocyclische Dicarbonsäureester, 4. Mitt. Zur Reaktion von 4,5-Dihydro-2,3-furandicarbonsäure-dimethylester mit Harnstoff. - Synthese von 5-(2-Oxo-tetrahydro-3-furanyliden)-hydantoinen

Heterocyclic Dicarboxylic Acid Esters, IV: Reaction of Dimethyl 4,5-Dihydro-2,3-furandicarboxylates with Urea. - Synthesis of 5-(2-Oxotetrahydro-3-furanylidene)hydantoins In the presence of sodium ethanolate the dihydrofurandicarboxylate 2 reacts with urea to form the hydantoin 7a . The structure is confirmed by spectroscopic data, catalytic hydrogenation and independent synthesis of 7a and the hydantoins 7b – g starting from α-ethoxalyllactones.