Aminoalkohole, 4. Mitt.: Ein Trennverfahren zur Herstellung von enantiomerenreinem Midodrin (original) (raw)
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Chemische Berichte, 1980
Die stickstoff-und sauerstoff-substituierten chiralen Diole 1 werden aus Weinsaure oder Apfelsaure hergestellt. Zur Einfuhrung der Aminogruppen werden von der Weinsaure abgeleitete Elektrophile rnit ansteigender Reaktivitat verwendet: der Diester (-+ 3), das Ditosylat 4 (+ S), das Diepoxid 6 (+ l a , e, g, h) und das Saurechlorid 7a. Die aus Apfelsaure erhaltlichen Alkylierungsmittel 9a und 1Oc dienen zur Synthese von l i . -Die Diole 1 werden rnit Lithiumalanat zu cyclisch formulierten chiralen Komplexen 2 umgesetzt, welche Ketone rnit prochiralem Carbonyl-C-Atom zu optisch aktiven Alkoholen reduzieren (Tab. 1 und 2). Aufgrund der Substituentenabhangigkeit und des Chiralitatssinnes der Produkte dieser asymmetrischen Synthese werden verschiedene Modelle 11 -16 fur den Mechanismus diskutiert.
Angewandte Chemie, 1996
106 pm', Z = 2, pber. = 2.78 g~m-~, T = 188 K, R = 0.083 fur 4533 unahhangige Reflexe (F > 4.Ou(F)).-Kristalldaten von 2: Pi, a =1282.0(4). b = 1380.3(4), c = 1531.515) pm, a = 83.46(2), j ! 3 = 77.37(2), y = 68.92(2)", V = 2466(3) x 10, pm3, Z = I , pber = 3.32 gcm-', T = 294 K, R = 0.067 fur 6614 unabhangige Reflexe (F > 4.0u(F)). Weitere Informationen zu den Kristallstrukturuntersuchungen konnen beim Fachinformationszentrum Karlsruhe, D-76344 Eggenstein-Leopoldshafen, unter Angabe der Hinterlegungsnummer CSD-59227 angefordert werden. Das Clusteranion 2 a konnte auch als Ammoniumsalz
Helvetica Chimica Acta, 1990
Glycolaldehyde phosphate aldomerizes in aqueous NaOH solution to a product mixture containing the racemates of the two diastereoisomeric tetrose 2,4-diphosphates and eight hexose 2,4,6-triphosphates. At room temperature in the absence of air and after 7 days, a solution 0 . 0 8~ in glycolaldehyde phosphate (= formylmethyl dihydrogenphosphate) and 2M in NaOH gives products, in up to 80% yield, with a tetrose/hexose derivative ratio of ca. 1 : 10 and with rue-allose 2,4,6-triphosphate comprising up to 50% of the mixture of sugar phosphates. When the reaction is run under the same conditions but in the presence of 0.5 mol-equiv. of formaldehyde, sugar phosphates are formed in up to 45% yield, with pentose 2,4-diphosphates now predominating over hexose triphosphates by a ratio of 3:1. rue-Ribose 2,4-diphosphate is found to be the major component, the ratios among ribose, arabinose, lyxose, and xylose 2,4-diphosphates being 52:14: 23: 11 in a representative experiment. The pentose diphosphates are constitutionally stable under the reaction conditions (observed for 23 weeks), but the diastereoisomeric ratios slowly change with time (to 22:34:30:14 after 23 weeks), showing that ribose 2,4-diphosphate is not the thermodynamically favored diastereoisomer. The observed product distributions in both the pentose and the hexose series (after 1 week) reveal an aldolization mode that is preferentially erythro in the product-determining step (the reaction of glycolaldehyde phosphate as its enolate with glycerinaldehyde 2-phosphate and tetrose 2,4-diphosphdte, respectively). An attempt is made to rationalize both this fact and the kinetic predominance of ribose 2,4-diphosphate in the pentose series and allose 2,4,6-triphosphate in the hexose series. Their configuration along the C-chain can be interpreted as corresponding to a minimum number of 1-5 repulsions in the packing of phosphate and OH substituents and minimal steric interaction between substituents at the reaction centers in the transition state of the product-determining step. The aldomerization of glycolaldehyde phosphate in the presence of formaldehyde is a variant of the formose reaction. It avoids the formation of complex formose product mixtures, largely as a consequence of the fact that aldoses which are phosphorylated at the C(2) 4. Mitteilung uber die Chemie von a -Aminonitrilen. 3. Mitteilung: [I].
Zur Aminolyse von Bis-Imidoylchloriden der Oxals�ure II. Umsetzung mit Diaminen und Aminoalkoholen
Journal für Praktische …, 2004
On the Aminolysis of Bis-Imidoylchlorides of Oxalic Acid. II. Reaction with Aliphatic Diamines and AminoalcoholsThe aminolysis of bis-imidoylchloride 1 derived from oxalic acid with several diamines and aminoalcohols was investigated. At room temperature diamines 2 as well as aminoalcohols 7 give mainly the cyclic amidines 3 and mixed amidine-imidates 8 in moderately up to good yields. While cis-1,2-diaminocyclohexane yields at room temperature the bicyclic amidine 3a, the trans isomer reacts to 3b only when heated for several hours. Depending on the conditions, the racemic 1,2-diaminopropane 2h gives derivatives of pyrazine 3h or the open-chain amidine 5 resulting from an oxidative aromatization and subsequent hydrolysis. Histamine 2i and 1,8-diamino-3,6-dioxaoctane 2p react selectively with 1 to seven- respectively twelve-membered heterocycles 3i and 3p. The mixed aliphatic and aromatic diamines 2n, o show an anomalous behaviour leading to 2,2′-bis-chinazolines 3n, o.In comparison with acyclic oxalic amidines the new cyclic derivatives show less molecular dynamic in their nmr spectra. In some cases, a s-trans-arrangement of the amidine substructure was observed.
Xylidin, Isomere (2,3-Xylidin, 2,5-Xylidin, 3,4-Xylidin, 3,5-Xylidin). MAK-Begründung, Nachtrag
2020
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated the xylidine isomers 2,3-, 2,5-, 3,4-and 3,5xylidine [87-59-2, 95-78-3, 95-64-7, 108-69-0] considering all toxicological end points. The critical effects are methaemoglobinaemia, anaemia and effects on the spleen, liver and kidneys. A carcinogenicity study was performed with only 2,5-xylidine. Although the study is of limited validity, the angiosarcomas observed in male mice and fibromas and fibrosarcomas in rats are tumours typical for aromatic amines. Therefore, a carcinogenic potential is assumed and 2,3-, 2,5-, 3,4-and 3,5-xylidine are classified in Carcinogen Category 3 B for suspected carcinogens. All four isomers are genotoxic both in vitro with metabolic activation and in somatic cells in vivo. However, these findings are not quite consistent, this is typical for aromatic amines. Therefore, 2,3-, 2,5-, 3,4-and 3,5-xylidine are classified in Category 3 B for germ cell mutagenicity. A maximum concentration at the workplace (MAK value) is not derived because of the suspected mutagenicity. There are only limited data for percutaneous absorption, but as the systemic toxicity of these four isomers is high and they are suspected mutagens and carcinogens, the designation with "H" is retained. Studies of the sensitization potential are not available.
Synthese von Dendrimeren durch Hydroaminomethylierung und ihre Anwendung
2004
Ende des 17. und Anfang des 18. Jahrhunderts fand die Aufspaltung, der bis dahin vo n " Universalgelehrten" betriebenen Forschung , in die eigenständigen Bereiche Mathematik, Physik, Biologie (Medizin) und Chemie, statt. Nach nunmehr zwei Jahrhunderten Spezialisierung in den einzelnen Fächern, werden in neuerer Zeit die Forschungsaktivitäte n der verschiedenen Wissenschaftsgebiete durch interdisziplinäres Zusammenwirken geprägt. In immer zahlreicheren Beispielen zeigt sich, wie sehr die einzelnen Wissenschaften miteinander verwoben sind und ähnliche Phänomene bearbeiten. Dies gilt in besonderem Maße für das Gebiet der dendritischen Systeme. In der Mathematik findet man sie als fraktale Mengen, in Medizin und Biologie z.B. in Form von Dendriten (cytoplasmatische Fortsätze an Nervenzellenoberflächen), Desmosomen (interzelluläre Vernetzungen) und Farne n. In der Physik spricht man von fraktalen Dimensionen, aufgrund von Untersuchungen an Partikeloberflächen 1 und in der Chemie sind sie neben theoretischen Abhandlungen 2 auch als hochverzweigte perfekte Strukturen unter dem Namen Dendrimere bekannt. 3-6 Einleitung und Problemstellung 2 1.2 Dendrimere in der Chemie Vor etwa Jahren legte Flory mit der Einführung der Theorie von unendlichen Netzwerken den Grundstein für den Aufbau von "Dendrimeren". i,7-11 Weitere theoretische Abhandlungen wurden im Jahre 1975 veröffentlicht. 12-14 Die erste Synthese einer, wie in den Theorien beschriebenen, regelmäßig verzweigten Struktur gelang hingegen erst 1978 durch die Arbeitsgruppe von Vögtle.
Helv Chim Acta, 1990
Glycolaldehyde phosphate aldomerizes in aqueous NaOH solution to a product mixture containing the racemates of the two diastereoisomeric tetrose 2,4-diphosphates and eight hexose 2,4,6-triphosphates. At room temperature in the absence of air and after 7 days, a solution 0 . 0 8~ in glycolaldehyde phosphate (= formylmethyl dihydrogenphosphate) and 2M in NaOH gives products, in up to 80% yield, with a tetrose/hexose derivative ratio of ca. 1 : 10 and with rue-allose 2,4,6-triphosphate comprising up to 50% of the mixture of sugar phosphates. When the reaction is run under the same conditions but in the presence of 0.5 mol-equiv. of formaldehyde, sugar phosphates are formed in up to 45% yield, with pentose 2,4-diphosphates now predominating over hexose triphosphates by a ratio of 3:1. rue-Ribose 2,4-diphosphate is found to be the major component, the ratios among ribose, arabinose, lyxose, and xylose 2,4-diphosphates being 52:14: 23: 11 in a representative experiment. The pentose diphosphates are constitutionally stable under the reaction conditions (observed for 23 weeks), but the diastereoisomeric ratios slowly change with time (to 22:34:30:14 after 23 weeks), showing that ribose 2,4-diphosphate is not the thermodynamically favored diastereoisomer. The observed product distributions in both the pentose and the hexose series (after 1 week) reveal an aldolization mode that is preferentially erythro in the product-determining step (the reaction of glycolaldehyde phosphate as its enolate with glycerinaldehyde 2-phosphate and tetrose 2,4-diphosphdte, respectively). An attempt is made to rationalize both this fact and the kinetic predominance of ribose 2,4-diphosphate in the pentose series and allose 2,4,6-triphosphate in the hexose series. Their configuration along the C-chain can be interpreted as corresponding to a minimum number of 1-5 repulsions in the packing of phosphate and OH substituents and minimal steric interaction between substituents at the reaction centers in the transition state of the product-determining step. The aldomerization of glycolaldehyde phosphate in the presence of formaldehyde is a variant of the formose reaction. It avoids the formation of complex formose product mixtures, largely as a consequence of the fact that aldoses which are phosphorylated at the C(2) 4. Mitteilung uber die Chemie von a -Aminonitrilen. 3. Mitteilung: [I].