Norbert Itzhak

Selective Functionalization of a Single Methylene Bridge of a Calix[6]arene

The monohydroxycalix[6]arene derivative 4a was prepared via photochemical bromination of hexamethoxycalix[6]arene 3a in aq THF. Monohydroxycalix[6]arene 4a and its chloro derivative 5 are useful synthetic intermediates for the preparation of structurally diverse calix[6]arenes functionalized at a single methylene bridge.

Calix[6]arenes incorporating functionalised substituents at the methylene bridges

The hexabromocalix[6]arene 5 reacts with p-tert-Bu-phenol, thymol and propargyl alcohol to afford the corresponding hexasubstituted methylene-functionalised calixarenes. The substituents at the bridges were further functionalised via acetylation or click chemistry. Reaction of the hexahydroxy derivative 10 with DAST afforded 11, a first example of a calixarene with all bridges monofluorinated.

Calixradialenes: calixarene derivatives with exocyclic double bonds.

Reaction of dioxocalix[4]arene 7 with MeLi followed by 2-fold elimination of water yielded calixarene 8 possessing exocyclic double bonds at two adjacent bridges. Calixarene 8 exists in tetrachloroethane-d2 solution at rt, as a 2.3:1 mixture of the 1,3-alternate and partial cone conformers. Keto[n]calixarenes (n = 5, 6) were prepared via hydrolysis of the bromocalixarenes 11 and 12, followed by CrO3 oxidation of the respective hydroxymethylene derivatives. Addition of MeLi to the ketocalix[n]arenes (n = 4, 5 and 6) followed by elimination of water yielded the corresponding calix[n]radialenes. Calix[5]- and calix[6]radialenes adopt in the crystal irregular alternate (i.e., noncone) conformations.

Reaction of mesoionic thiazol-4-ones with azodicarbonyl dipolarophiles. Cleavage modes of the bi- and tri-cyclic adducts

The thiazolium-4-olates (1a–e) were treated with dimethyl and diethyl azodicarboxylate and gave, through 1,3-dipolar cycloaddition, the 3,6-sulphur bridged hexahydro-1,2,4-triazin-5-ones (2). When heated in benzene these rearranged to the blue thioxohydrazides (3), whilst when heated in methanol or ethanol they reacted with the solvent to give 2-alkoxy-5-hydrazinothiazol-4-ones (4). Reaction of the mesoionic compounds (1) with 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) gave the cycloadducts (11) which reacted very readily with water or alcohols to give the thiazol-4-ones (5), analogous to (4). The structures and stereochemistry of (2), (3), and (5) were established by X-ray analyses. The mechanisms of the ring openings of (2) to (3) and (4), and of (11) to (5) are discussed.

Reaction of carbanions with N-tosyloxyphthalimide. Formation of 3,3-disubstituted quinoline-2,4-diones

The reaction of a series of carbanions, including both aromatic anions and enolate anions, with N-tosyloxyphthalimide gave 3,3-disubstituted quinoline-2,4-diones. A multi-step mechanism which involves attack of the carbanion on a carbonyl group, ring opening, Lossen-like rearrangement, intermolecular proton transfer, and ring closure is suggested.

Cycloaddition of nitroso dipolarophiles to thiazolium-4-olates. Part 1. Nitrosobenzene and 1-chloro-1-nitrosocyclohexane

Thiazolium-4-olates 1 and nitrosobenzene participated in regiospecific cycloadditions which gave 3-oxa-2,5-diaza-7-thiatrinorbornan-6-ones 5. On storage, compounds 5 rearranged to the azeto-benzothiazine S-oxides 7, fragmented to the benzil diimides 8, and a lost sulfur atom to give the iminoimides 9. The cycloadditions of mesoionic compounds 1 with 1-chloro-1-nitrosocyclohexane exhibited a reversed regiochemistry and formed the trinorbornanes 6, which were subsequently attacked by nucleophiles at the bridgehead to produce the thiazolones 14. The mechanisms of formation of all the products are discussed. Structures 7a and 14d were confirmed by single-crystal X-ray analyses.

Desulphuration of sulphur bridged hexahydrotriazines: ring contraction to imidazolidines

Raney nickel desulphuration of 6-aryl-2,3-bis(methoxycarbonyl)-1,4-diphenyl-7-thia-2,3,6-triazanorbornane-5-ones (1a,b) yielded mainly 3-aryl-1-benzoyl-5-(methoxycarbonylamino)-5-phenylimidazolidine-2,4-diones (3a,b). A mechanism which involves six alternating ring-opening and ringclosure steps is suggested. Evidence in favour of this unusual pathway include the following: (a) structure of the minor products (4). (b) Desulphuration of the 6-benzyl derivative (1c), which allowed isolation of the intermediate (11c). (c) Desulphuration of the analogous sulphur bridged pyridone (15), which gave the dihydropyridone (17). Structures (3b), (11c), and (17) were confirmed by X-ray analyses.

Reactions of Mesoionic Thiazolones with Nitroso-Dipolarophiles

Abstract Reactions of a series of thiazolium-4-olates with nitrosobenzene, with 1-chloro-1-nitrosocyclohexane and with acylnitroso derivatives, gave initially strained bicyclic cycloadducts. These, upon heating, underwent some unusual rearrangements and fragmentations.