2,4‐Dioxa‐, 2,4,9‐Trioxa‐, 2,4‐Dioxa‐9‐aza‐, 2‐Oxa‐4,9‐diaza‐und 2,4,9‐Triazaadamantane

Abstract

Die Umsetzung der Trihalogenide 7a, b mit Natriumcyanid in Dimethylformamid ergab das Cyclopropandicarbonitril9 anstelle des Trinitrils 7c, das als Vorstufe von 2,4,9-Triazaadamantanen dienen sollte. Die Photolyse und Thermolyse des bemerkenswert stabilen Triazids 13c verliefen unubersichtlich durch Bildung nicht identifizierbarer Produkte, unter denen das Triazaadamantan 6a oder Hydrolyseprodukte des Triimins 14 nicht aufzufinden waren. Das leicht cyclisierende Triketon 31 wurde aus dem Trisaurechlorid 3 k mit iiberschussigem Lithiumdimethylcuprat nach schonender Aufarbeitung erhalten und erwies sich als Schlusselverbindung fur neue Heteraadamantane: Methanolat bewirkte intramolekulare Aldoladdition und Cyclisierung von 31 zum 2,4-Dioxaadamantan 15. Uberschussiges flussiges Ammoniak uberfuhrte 31 fast quantitativ in das 2,4-Dioxa-9-azaadamantan 16a. Das gleiche Ringsystem (16b) wurde aus 31 und 12 mol Hydrazinhydrat gebildet. Dagegen erhielt man aus 31 mit einem sehr hohen UberschuR Hydrazinhydrat das 2-0xa-4,9-diazaadamantan 16c. Wasserfreies Hydrazin in trockenem Ethanol und 31 ergaben schlieRlich das 2,4,9-Triazaadamantan 16d. Die Strukturen der neuen Verbindungen wurden IR-und NMR-spektroskopisch gesichert. Laut LAOCOON-111-Analyse kommen die komplexen 'H-NMR-Multipletts der Methylenprotonen von 15 und 16a -c nur durch W-Kopplungen von 2 -3 Hz und geminale Kopplungen zustande.2,4-Dioxa-, 2,4,9-Trioxa-, 2,4-Dioxa-9-aza-, 2-0xa-4,9-diaza-, and 2,4,9-Triazaadamantanes l)The reaction of the trihalides 7a, b with sodium cyanide in dimethylformamide afforded the cyclopropanedicarbonitrile 9 instead of the tricarbonitrile 7c which had been designed as a precursor to 2,4,9-triazaadamantanes. Both the photolysis and thermolysis of the remarkably stable triazide 13c proceeded in an ill-defined way, producing unidentifiable products among which neither the triazaadarnantane 6a nor hydrolysis products of the triimine 14 could be detected. The readily cyclizing triketone 31 was obtained from the reaction of the tricarbonyl chloride 3k with an excess of lithium dimethylcuprate followed by careful work-up. It proved to be the key to several novel heteraadamantanes: Thus, methoxide brought about an intramolecular aldol addition and cyclization of 31 to the 2,4-dioxaadamantane 15. An excess of liquid ammonia converted 31 into the 2,4-dioxa-9-azaadamantane 16a almost quantitatively. The same ring system (16b) was formed in the reaction of 31 with 12 mol of hydrazine hydrate. In contrast, the reaction of 31 with a very large excess of hydrazine hydrate afforded the 2-oxa-4,9-diazaadamantane 16c. Finally, 31 reacted with dry hydrazine in ethanol to yield the 2,4,9-triazaadamantane 16d. The structures of the new compounds were established by IR and NMR spectroscopy. Analysis of the complex 'H NMR multiplets of the methylene protons of 15 and 16a -c by LAOCOON 111 shows that they arise exclusively from W-couplings of 2 -3 Hz and geminal couplings.

2,4,9‐Triazaadamantanes with “Clickable” Groups: Synthesis, Structure and Applications as Tripodal Platforms

“…Selective synthesis of 2,4,9‐triazaadamantanes is challenging and only two reports have dealt with this problem. The first 2,4,9‐triazaadamantane derivative (TRIAD 2a ) was obtained by Quast and Berneth [ 25a ] in 1983 by treatment of tris‐ketone 1a with ca. 60 equiv.…”

“…Due to an irreversible intramolecular cyclization of the tris‐ketone and the intermediate mono‐ and bis‐hydrazones, the yield of the desired triazaadamantane 2a was only 26 %. Recently, Luo and co‐workers [ 25b ] reported the synthesis of tris‐benzyl TRIAD 2b via trial 1b . The later was generated by Stetter's method, [ 26 ] which involves ozonolysis of triallylcarbinol 3b followed by hydrogenolysis of ozonide over Pd/BaSO 4 at r.t. (Scheme 2, chart b).…”

“…Unlike the procedures of Stetter [ 26 ] and Luo, [ 25b ] in which ozonide was cleaved by catalytic hydrogenation at room temperature, we used reduction with Me 2 S to generate tris‐carbonyl compounds 1b – e at –78 °C. Furthermore, N ‐nucleophile was added together with the Me 2 S to ensure maximum conversion of the tris‐carbonyl compound into the corresponding tris‐imine (Scheme 3).…”

“…Furthermore, N ‐nucleophile was added together with the Me 2 S to ensure maximum conversion of the tris‐carbonyl compound into the corresponding tris‐imine (Scheme 3). These modifications resulted in much better yields of triazaadamantanes 2 compared to the previous procedures by Quast [ 25a ] and Luo [ 25b ] (vide infra). In all cases, an excess of the N ‐nucleophile was needed, as it also reacted with formaldehyde, which was formed as a by‐product of the alkene ozonolysis.…”

“…Unsubstituted 2,4,9‐triazaadamantane is unknown, [ 18b ] and to date, only six of its derivatives have been reported in the scientific and patent literature. [ 25 ] In this work, we attempted to develop a convenient method for the synthesis of 2,4,9‐triazaadamantanes bearing “clickable“ groups on nitrogen atoms as potential platforms for the construction of functional molecules. We also performed preliminarily studies on the structure, stability, and transformations of this novel class of heterocage compounds.…”