Zwitterions as Intermediates in 1,3‐Dipolar Cycloadditions of Electrophilic Azides to 2‐Alkylidenetetrahydroimidazoles and 2‐Alkylidenedihydrobenzimidazoles

Abstract

Cyclic ketene N,N-acetals derived from imidazolidine (4a, c) and 2,3-dihydrobenzimidazole (6a-c) add methanesulphony1 azide (2a) or picryl azide (2f) to afford the zwitterions 5 and 7, respectively. The structure of 7d is elucidated by X-ray crystallography. Reversibility of formation and thermal stability of the N-sulphonyl zwitterions depend on the substitution pattern at the carbon atom to which the triazenide moiety is attached: In the case of a pair of geminal methyl groups (5a, ?a) formation is irreversible and decomposition by cyclisation and subsequent reactions occurs above -2O"C, while in presence of a single alkyl group (7c, d) these processes require heating to 80°C and are accompanied by partial reversion to 2a and ketene N,N-acetals (6b, c). into N-sulphonylimine 13 and diazo compound 14 or extrude molecular nitrogen to furnish ring-expanded 2-(sulphonylimino)piperazine derivatives (9, 11).According to experimental criteria, the vast majority of 1,3-dipolar cycloaddition reactions proceed by a concerted Ten years ago, the first limiting case of a nonconcerted 1,3-dipolar cycloaddition has been realised by Huisgen and coworkers when they treated (strongly nucleophilic) thiocarbonyl ylides with strongly electrophilic dipolarophiles. The resulting zwitterions were demonstrated to be true intermediates in [3 + 21 cycloaddition reactions"]. More recently, we have disclosed first examples of the second case, which limits the scale of orbital interactions at the opposite side, when electrophilic dipoles, viz. sulphonyl azides 2a-c and nitroaryl azides 2d-f, were allowed to react with strongly nucleophilic dipolarophiles, i.e. alkylidenedihydrotetrazoles (1). Zwitterions 3 arose as primary products, and their thermal stability varied over a wide range[4-61. Conclusive evidence has been adduced for the role of the zwitterions 3a and c as intermediates in twostep 1,3-dipolar cycloaddition~ [~]. We now report that other cyclic ketene NN-acetals, namely alkylidenetetrahydroimidazoles 4 and alkylidenedihydrobenzimidazoles 6, also react with electrophilic azides (2a, f) to afford zwitterions 5, 7 which closely resemble those obtained from alkylidenedihydrotetrazoles 1.Cyclic ketene NN-acetals whose nitrogen atoms are connected by a bridge, like alkylidenedihydvotetrazoles 1, -imidazole~[~I, and -benzimidazoles 6 as well as alkylidenetetrahydroimidazoles 4, possess extremely electron-rich nucleophilic terminal carbon atoms which may be regarded as anionic part of ylidic systems. This property is reflected

Ring Expansion vs. Cleavage of the Exocyclic Double Bond of 2-Cycloalkylidenedihydrobenzothiazoles and -benzimidazoles by Methanesulfonyl Azide

“…Ring expansion to the spirocyclic tetrahydroquinoxalines 13f-h occurred to the same or greater extent as cleavage to the N-methylsulfonylimine 14, rendering this sequence as a useful ring expansion method ( Table 1). The occurrence of benzimidazolium ions, which would indicate reversibility of the zwitterion formation, [2] was not observed when the thermolysis of 12f-h was monitored by proton spectroscopy. This is a further difference between these zwitterions and the cyclopropyl zwitterion 12e.…”

“…of type 2a-d and 11b-d, readily add electrophilic azides such as methanesulfonyl azide (3, Schemes 1 and 2). While 2-alkylidenedihydrobenzimidazoles 11b-d yield zwitterions 12 (Scheme 2), which can be isolated in most cases, [2] the adducts of the benzothiazole derivatives 2a-d (and other heterocycles) with 3 immediately loose molecular nitrogen and undergo ring expansion, or are cleaved into N-sulfonylimine 5 and a diazo compound 6. The zwitterions 12b-d behave likewise, but in general only at higher temperatures.…”

“…The zwitterions 12b-d behave likewise, but in general only at higher temperatures. Previous studies have uncovered structural features that favour the useful ring expansion reaction over the undesired diazoalkane cleavage: [3,4] Soft heteroatoms like sulfur and selenium, whose tendency to form bridged cations is wellknown, [5] and one alkyl group or, better, two methyl groups at the exocyclic carbon atom of the heterocyclic N,X-acetals as in 2b-d and 11b-d favour ring expansion. We have now used two representative 2-alkylidene heterocycles, whose exocyclic carbon atom is a member of a cycloalkane ring, to study the effect of the size of that ring.…”

Ketene-N,N-acetals as Key Intermediates in the Formation of Tetraazapentafulvadienes

“…[1Ϫ9] These compounds are suspected to possess a large charge density at the β-carbon, as observed experimentally by their photoelectron spectra [9] and the well-documented 13 C NMR upfield shift of the β-carbon. [6Ϫ8] These derivatives possess dipolarophilic qualities, [10] are strong neutral bases [6,7] and reactive nucleophiles, [6Ϫ9] and have been employed as dienophiles in inverse electron demand DielsϪAlder reactions. [6,7] In spite of these interesting electronic properties, synthetically useful oxidation reactions [11Ϫ13] involving ketene-N,N-acetals are practically unknown.…”

Ring Expansion of 2-Alkylidenedihydroquinolines to 2-Iminodihydro-1-benzazepines by Phenyl, Methanesulphonyl, and Trifluoromethanesulphonyl Azide[1]

“…[7] With the view of defining the parameters that determine the course of the reactions between alkylidenedihydroquinolines 2 and azides, and optimising the conditions for iminodihydro-1-benzazepine formation, we investigated the reactions of phenyl (9), methanesulphonyl (18a), and trifluoromethanesulphonyl azide (18b) with 2-alkylidenedihydroquinolines whose substitution pattern differ from those employed by Sato et al [5] The electron-deficient azides allowed us to trap 2, which were generated from N-methylquinolinium salts 1 by deprotonation with sodium or potassium hydride. Last but not least, these experiments were stimulated by the prospect of an efficient synthesis of 5-aryl-2-iminodihydro-1-benzazepines, [8] which are related to SternbachЈs 5-aryl-1,4-benzodiazepines, whose pharmacological importance cannot be overestimated.…”