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

Abstract

5-(a-Diazoethyl)tetrazoles, Methyl Tetrazol-5-yl Ketone Hydrazones, Silver(I) Oxide, D ehydrogenationHydrazone dehydrogenation with silver(I) ox ide in the presence of sodium hydroxide was found an efficient approach to the title com pounds, whereas application of the Bamford-Stevens reaction proved unsatisfactory.In connection with rearrangem ent studies in the 1,2,3-triazole series [1] we needed authentic sam ples of certain 5-(a-diazoethyl)tetrazoles, viz. 1 and 5 and the anion of 9. 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. We therefore attem pted the short approach iii.The requisite ketones 2, 6 and 10 (precursors to the tosylhydrazones 3, 7 and 11) are readily avail able. As for 2 (a still unknown tetrazole), the straightforward sequence 13 -* 14 -» • 15 -* 2 based on standard procedures [6] was used. The isomer 6 could easily be made from the nitrile 17 (obtain able as m ajor product by methylation of 16 [7]). 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. We found that for a success ful transform ation 12 -* 9 the sodium salt of 12 is required (rather than...

Rearrangement of substituted azido-1,2,3-triazolides to (α-diazoalkyl)tetrazolides

“…)-Me 2 SO or (CD 3 ) 2 SO; rt or 32 ЊC was added to the above solution to give a mixture that showed the tetrazoles 7b and 8b as main components (see Table 1; the NMR shift values quoted agreed with those of authentic specimens 13 ). A similar methylation reaction was also performed with 6c-g; in these cases purity of 7/8 was accordingly higher (assignments of peaks in Table 1 were based on the assumption that, as with 8a 3,14 and 8b, 13 the methyl protons of the 2H-isomer 8 resonate at lower field).…”

A Click Chemistry Approach to Tetrazoles by Huisgen 1,3-Dipolar Cycloaddition: Synthesis of 5-Acyltetrazoles from Azides and Acyl Cyanides We thank the National Institute of General Medical Sciences, National Institutes of Health (GM-28384), the National Science Foundation (CHE-9985553), the Skaggs Institute for Chemical Biology for a Predoctoral Fellowship (Z.D.), and the W. M. Keck Foundation for financial support.

“…As dozens of acyl cyanides are commercially available, and countless more are available in one step from acyl halides, great diversity can be rapidly accessed with this cycloaddition. In addition, further important synthetic transformations are immediately available through the active aryl‐ketone moiety, oxime, and hydrazone derivatives, for example 15…”