A new generation of alkoxyl radical precursors - Preparation and properties of N-(alkoxy)-4-arylthiazole-2(3H)-thiones

N-(Hydroxy)thiazole-2(3H)-thiones 6-10 have been prepared in a short and ef ficient synthesis from p-substituted acetophenones. Alkylation of heterocyc les 6-10 in the form of their potassium or tetraalkylammonium salts 11-15 a ffords N-alkoxy-4-arylthiazole-2(3H)-thiones 16-20 in good to satisfactory yields. The hitherto unknown thiones 16-20 have been subjected to a detaile d structural investigation (NMR spectroscopy and X-ray crystallography) and furthermore to a mechanistic study in order to explore their utility as so urces of oxygen-centered radicals in solution, From the results of these st udies, the following conclusions can be drawn: (i) X-ray analyses of the p- chlorophenyl-substituted acid 9, of the O-alkyl derivatives 19c, 19f, and o f the O-mixed anhydride 19k indicate short C-S bonds [C2-S2 = 1.637(5)-1.68 4(2) Angstrom] and long N-O connectivities [N3-O1 = 1.369(3)-1.379(2) Angst rom] in the thiohydroxamate functionalities. Furthermore, O-alkyl- or O-acy l substituents at O1 are twisted out of the thiazolethione plane by ca, 90 degrees, which points to lone-pair repulsion between nitrogen and oxygen at om as the underlying structural motif of the cyclic thiohydroxamate derivat ives. (ii) Alkylation of ambidentate thiohydroxamate anions (salts 11-15; o xygen and sulfur nucleophiles) affords almost exclusively O-esters 16-20 (a lkylation at the oxygen atom). (iii) Based on the results of X-ray diffract ion studies and on the H-1- and C-13-NMR spectra, guidelines for the charac terization of N-(alkoxy)thiazolethiones 16-20 and 2(alkylsulfanyl)thiazole N-oxides 21-25, i.e. the products of S-alkylation of thiohydroxamate salts 11-15, could be derived. (iv) Photolyses of substituted N- (4-pentenoxy)-4- arylthiazolethiones 16-20 in general and in particular of p-chloro derivati ves 19 were carried out in the presence of the hydrogen donor Bu3SnH, and a fforded substituted tetrahydrofurans 31 or tetrahydropyrans 32 as major pro ducts in good yields. The observed stereo- and regioselectivities of ethers 31 and 32 point to alkoxyl radicals 30 as reactive intermediates, which ad d intramolecularly by selective 5-exo-trig or 6-endo-trig pathways to the o lefinic double bonds. In terms of synthetic access and ease of handling of the radical precursors, the p-chlorophenyl-substituted thiazolethiones 9 an d 19 exhibit significant advantages over all the other thiones used in this study and are considered as excellent substitute's for the pyridinethiones as efficient sources of free alkoxyl radicals. Consequently, the present c ompounds may be of use in both mechanistic and synthetic studies.