First Examples of Reactions of AzoleN-Oxides with Thioketones: A Novel Type of Sulfur-Transfer Reaction

Abstract

The reactions of 1,4,5‐trisubstituted imidazole 3‐oxides 1a – k with cyclobutanethiones 5a,b in CHCl3 at room temperature give imidazole‐2(3H)‐thiones 9a – k in high yield. The second product formed in this reaction is 2,2,4,4‐tetramethylcyclobutane‐1,3‐dione (6a; Scheme 2). Similar reactions occur with 1 and adamantanethione (5c) as thiocarbonyl compound, as well as with 1,2,4‐triazole‐4‐oxide derivative 10 and 5a (Scheme 3). A reaction mechanism by a two‐step formation of the formal cycloadduct of type 7 via zwitterion 16 is proposed in Scheme 5. Spontaneous decomposition of 7 yields the products of this novel sulfur‐transfer reaction. The starting imidazole 3‐oxides are conveniently prepared by heating a mixture of 1,3,5‐trisubstituted hexahydro‐1,3,5‐triazines 3 and α‐(hydroxyimino) ketones 2 in EtOH (cf. Scheme 1). As demonstrated in the case of 9d, a `one‐pot' procedure allows the preparation of 9 without isolation of the imidazole 3‐oxides 1. The reaction of 1c with thioketene 12 leads to a mixture of four products (Scheme 4). The minor products, 9c and the ketene 15, result from an analogous sulfur‐transfer reaction (Path a in Scheme 5), whereas the parent imidazole 14 and thiiranone 13 are the products of an oxygen‐transfer reaction (Path b in Scheme 5).

Reactions of 2-Unsubstituted 1H-Imidazole 3-Oxides with 2,2-Bis(trifluoromethyl)ethene-1,1-dicarbonitrile: A Stepwise 1,3-Dipolar Cycloaddition

“…1b-f have already been described [7][11] [33]. Compounds 1g-i, which have not been described so far, were prepared by heating 1.2 mmol of the corresponding 1,3,5-hexahydrotriazine 9 with 1.0 mmol of 3-(hydroxyimino)-3-phenylpropan-2-one (8, R 1 = Me) and α-benzil monoxime (8, R 1 = Ph), respectively, in boiling EtOH.…”

“…Convenient syntheses of 2-unsubstituted imidazole N-oxides are condensations of α-(hydroxyimino)ketones with in situ generated methylidenamines [7], of α-aminooximes with orthoformates [8], and of diimines with formaldoxime [9]. Generally, imidazole N-oxides are not available by direct oxidation of the parent compound.…”

“…However, a recent paper describes the preparation of 1-methylimidazole N 3 -oxide by treatment of 1-methylimidazole in THF with H 2 O 2 at room temperature [10]. Starting with imidazole Noxides, preparations of imidazole-2-thiones [7], 2-cyanoimidazoles [11], as well as parent imidazoles via deoxygenation with PCl 3 [12] were reported. Furthermore the isomerization to…”

“…In fact, they react with dipolarophiles, such as dimethyl acetylenedicarboxylate [2] [12], isocyanates and isothiocyanates [2], as well as with thioketones and thioketenes [7] to give ultimate products, which result from subsequent conversions of the initially formed [2+3]-cycloadducts. Of special mechanistic interest is the reaction of 1a with thioketene 2, in which the formation of two sets of products, i.e.…”

“…is an indication for the stepwise reaction pathway [7] (Scheme1). The addition of the dipole 1 to the heterocumulene 2 leads to the zwitterionic intermediate A, in which the formation of the five-membered unstable cycloadducts (route a) competes with the cyclization to yield thiirane 4 (route b).…”