Vergleich 1‐ und 2‐substituierter 5‐(Diazomethyl)tetrazole

Abstract

Bedingt durch Resonanz-und elektrostatische Feldeffekte, geht vom 1-substituierten 5-Tetrazolyl-System (I) ein starkerer Elektronenzug aus als vom 2-substituierten (11)'). Hiervon zeugt in anschaulicher Weise die relative Reaktivitat zahlreicher I-und 11-verknupfter funktioneller Grupped). Nach eigenen Erfahrungen solcherart mit isomeren Tetra~olcarbaldehyden~) und -carbonitrilen4), ferner bestimmten Tetrazolylnitr~nen~) und Pyridinium-(tetrazolylmethyliden)6) sowie mit (Chlorrnethyl)tetrazolen"), interessierten uns als weitere Demonstrationsobjekte die bisher nicht beschriebenen Diazoverbindungen 1 und 2 das Verhalten der auf Anderungen der Bindungsnachbarschaft empfindlich reagierenden Funktion -C H N p sollte den verschiedenen EinfluD der beiden Heterocyclen besonders klar hervortreten lassen. Von entsprechenden Beobachtungen') handelt der folgende Bericht. R I II SyntheseWie zu erwarten, wird die unterschiedliche Aktivierung seitens der Tetrazolringe 1 und I1 bereits bei der Herstellung der gewunschten Verbindungen sichtbar:Wendet man auf die z.T. bekannten') Salze 7 und 8 das Verfahren der Amin-Diazotierung an und extrahiert die Ansatze sofort mit Dichlormethan, so findet man von den starker elektronegativ substituierten Diazoverbindungen 1 stets grooere Mengen als von den Isomeren 2. Im ersten Fall betragt der Quotient Diazoalkanbildung : Desaminierung etwa 1.7-2.5, irn zweiten schwankt er zwischen den Extremwerten ca. 0.3 (R = Me) und 1.3 (R = 4-02NC6H4). Der praparative Nutzen der Methode erstreckt sich damit The hitherto unknown title compounds 1 and 2 -readily obtained by m i n e diazotation (1) and Bamford-Stevens reaction (1, 2), respectively -show expected differences in both spectroscopic (UV/VIS, IR) and reactive behaviour towards (a) acids and electrophiles, (b) cycloaddition partners, (c) nucleophiles as well as (d) under thermolytic conditions leading to carbenes. Due to the more pronounced electron-withdrawal of the tetrazolyl system I, the isomers 1 react more slowly than 2 in cases (a) and (b), while with (c) and (d) the order is reverse. -The compounds 1 exhibit a certain sensitivity towards aqueous alkali (loss of the CHNl function).vornehmlich auf die Isomerenreihe 1. Fiihrt man hier die Reaktion im Essigsaure-Acetat-Puffer ohne organisches Solvens durch (Schema 1, Tab. 5), entfallen Trennungen, da die Desaminierungsprodukte (hauptsachlich 11, etwas 13 und vereinzelt wenig 3 -ihr Anteil steigt von R = Aryl nach R = Alkyl) weitgehend in Losung bleiben. Die weniger saurefesten Verbindungen 2 (vgl. Tab. l), allerdings auch der wasserlosliche Vertreter 1 a, sind nach dieser bequemen Variante jedoch nicht erhaltlich das Ergebnis entsprechender Versuche waren im wesentlichen l l a , 12 und 13a, 14.Anders als beim voranstehenden Verfahren hatte man durchgehend Erfolg mit der Bamford-Stevens-Reaktion") (Schema 1, Tab. 5). Fur die Titelverbindungen 1 genugt bereits die Einwirkung von Natriumcarbonat auf die betreffende Vorstufe 17, und zwar auf deren (E)-Isomeres (s.u.). In der Reihe der Tetrazole ...

Homologation Reaction of Ketones with Diazo Compounds

“…1- and 2-substituted 5-(diazomethyl)­tetrazoles were reported to undergo nucleophilic addition to isatins followed by ring expansion in the presence of either sodium hydroxide solution or HCl. The corresponding 3-hydroxyquinolinones 61 containing a tetrazole moiety were obtained in reasonable yields (54–63%). , …”

The chemistry of isatins: a review from 1975 to 1999

“…Diazoalkanes, such as diazomethane 458 and diazoarylalkanes 459,460 add to isatin at the C-3 position, leading to a carbinol that suffers a ring expansion to give the corresponding quinolone 461 (Scheme 114).…”

On the Preparation of 5-(α-DiazoethyI)tetrazoles

“…While detailed knowl edge is available for preparing a wide variety of diazoalkanes [2], experience in making tetrazolylsubstituted types is limited. Known routes starting from tetrazoles as substrates include (/) diazo transfer [3] and -for (diazower/zyOtetrazolesfunctional group transform ation such as (ii) amine diazotization in weakly acidic media [4], (Hi) the Bamford-Stevens reaction [1,4] and (iv) alkaline cleavage of N-alkyl-N-nitrosourethanes [4,5]. A p plication of m ethod i requires either an additional activating substituent (usually an acyl group) or an enamine function, m ethod ii should be ineffectual with 5 and 9, and m ethod iv requires an elaborate educt synthesis.…”

“…This route was given preference over a literature m ethod that starts from the carboxylic ester (17: C 0 2Et in place of CN) [8], because in that case * Reprint requests to Prof. Dr. D. Moderhack. the educt (likewise made via ring methylation) was later shown to consist of an inseparable 1:1 mix ture of 1-and 2-methyl isomers [7,9] and, hence, has been used impure [8], For the ketone 10, an expedient synthesis (akin to that shown for 6) has lately been published [10].When the tosylhydrazone 3 was treated in the m anner described for the analogous aldehyde de rivative [4], only traces of the desired diazo com pound 1 (if any) were formed, although for this reaction the more favourable (£')-isomer of 3 was employed [11], In the case of 11, the variant that earlier proved effective with the ring-unsubsti tuted aldehyde congener [1] was tried [i.e., brief heating (< 5 min) with DBN ( 1,5-diazabicyclo-[4.3.0]non-5-ene) in DMSO as solvent], but here too our efforts remained unrewarded. Since under these conditions also both 3 and 7 [the latter avail able in (Z)-form only] turned out to be unsuitable candidates, we converted the above ketones into the hydrazones 4, 8 and 12 [12], When these deriv atives were treated with silver(I) oxide in the pres ence of sodium hydroxide, a smooth reaction oc curred to produce the expected m aterials 1, 5 and 9 in reasonable yield.…”

“…When the tosylhydrazone 3 was treated in the m anner described for the analogous aldehyde de rivative [4], only traces of the desired diazo com pound 1 (if any) were formed, although for this reaction the more favourable (£')-isomer of 3 was employed [11], In the case of 11, the variant that earlier proved effective with the ring-unsubsti tuted aldehyde congener [1] was tried [i.e., brief heating (< 5 min) with DBN ( 1,5-diazabicyclo-[4.3.0]non-5-ene) in DMSO as solvent], but here too our efforts remained unrewarded. Since under these conditions also both 3 and 7 [the latter avail able in (Z)-form only] turned out to be unsuitable candidates, we converted the above ketones into the hydrazones 4, 8 and 12 [12], When these deriv atives were treated with silver(I) oxide in the pres ence of sodium hydroxide, a smooth reaction oc curred to produce the expected m aterials 1, 5 and 9 in reasonable yield.…”