N‐(Hydroxy)thiazole‐2(3H)‐thiones 6–10 have been prepared in a short and efficient synthesis from p‐substituted acetophenones. Alkylation of heterocycles 6–10 in the form of their potassium or tetraalkylammonium salts 11–15 affords 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 detailed structural investigation (NMR spectroscopy and X‐ray crystallography) and furthermore to a mechanistic study in order to explore their utility as sources of oxygen‐centered radicals in solution. From the results of these studies, 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 of the O‐mixed anhydride 19k indicate short C–S bonds [C2–S2 = 1.637(5)–1.684(2) Å] and long N–O connectivities [N3–O1 = 1.369(3)–1.379(2) Å] in the thiohydroxamate functionalities. Furthermore, O‐alkyl‐ or O‐acyl substituents at O1 are twisted out of the thiazolethione plane by ca. 90°, which points to lone‐pair repulsion between nitrogen and oxygen atom as the underlying structural motif of the cyclic thiohydroxamate derivatives. (ii) Alkylation of ambidentate thiohydroxamate anions (salts 11–15; oxygen and sulfur nucleophiles) affords almost exclusively O‐esters 16–20 (alkylation at the oxygen atom). (iii) Based on the results of X‐ray diffraction studies and on the 1H‐ and 13C‐NMR spectra, guidelines for the characterization 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 derivatives 19 were carried out in the presence of the hydrogen donor Bu3SnH, and afforded substituted tetrahydrofurans 31 or tetrahydropyrans 32 as major products in good yields. The observed stereo‐ and regioselectivities of ethers 31 and 32 point to alkoxyl radicals 30 as reactive intermediates, which add intramolecularly by selective 5‐exo‐trig or 6‐endo‐trig pathways to the olefinic double bonds. In terms of synthetic access and ease of handling of the radical precursors, the p‐chlorophenyl‐substituted thiazolethiones 9 and 19 exhibit significant advantages over all the other thiones used in this study and are considered as excellent substitutes for the pyridinethiones as efficient sources of free alkoxyl radicals. Consequently, the present compounds may be of use in both mechanistic and synthetic studies.

O‐Alkylation of cyclic thiohydroxamic acids 1 and 3–5 has been studied with a view to developing an efficient method for the synthesis of N‐(alkoxy)pyridine‐2(1H)‐thiones and N‐(alkoxy)thiazole‐2(3H)‐thiones. Four issues have been addressed and the following conclusions can be drawn: (i) Thiones 1 and 5 exist as O–H acids in the solid state. (ii) According to NMR investigations (1H, 13C), the thione structures should be largely retained in CDCl3, [D6]DMSO, and CD3OD solutions of acids 1, 3–5, as is also the case for pyridinethione salts 2a–h. (iii) O‐Alkylation of pyridinethione salts occurs in competition with S‐alkylation. Selective O‐alkylation is however possible, if thiohydroxamate salts with large countercations, such as M = NBu4, are treated with hard alkylating reagents in polar aprotic media. (iv) As tetrabutylammonium thiohydroxamates, such as 2f, are highly useful in the synthesis of cyclic thiohydroxamic acid O‐esters, we have developed an efficient protocol for the preparation of N‐(alkoxy)pyridine‐2(1H)‐thiones directly from acid 1 using phase‐transfer conditions (alkyl halide or sulfonic acid ester, CH3CN, K2CO3, Bu4NHSO4). This method has proved particularly successful for the synthesis of N‐(alkoxy)thiazole‐2(3H)‐thiones 11, 20–28, which were obtained in yields of up to 87%.

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Although Barton's radical precursors, the 0-acyl derivatives of 1-hydroxypyridine-2( 1H)-thione 2, have been studied in detail for more than a decade, to date nothing has been reported on the solid state or the solution geometries of these molecules or the analogous 0x0 derivatives, the pyridones 7, 8. In view of this, selected 0-alkyl and 0-acyl derivatives of pyridinethiones and of 2-( 1H)pyridones have been prepared and investigated by X-ray diffraction and NMR (COSY, NOE) experiments. The X-ray data indicate alternating bond lengths in the carbon framework of the heterocycles 2d, 3b, 7b, and 8 and long N -0 bonds [1.384(4)-1.398(2) A], In all the compounds studied, the 0-alkyl and the 0-acyl groups are twisted out of the plane of the heterocycles, which is in accord with the VSEPR concept. Further, the thermal stabilities of thiohydroxamic acid derivatives 2, 3 and of substituted pyridones 7, 8 were studied by differential scanning calorimetry (DSC).Alkyl esters 2[l,*] of 1 -hydroxypyridine-2( 1H)-thione (l)I3I, or the mixed anhydrides 3[41, serve as useful and versatile precursors of heteroatom and of carbon centered radicals 4 and 5I5l. The convenience of the use of the heterocyclic compounds 3 in synthetic radical chemistry originates from the fact that several procedures for the eficient in situ preparation of 3 have been elaborated which do not require isolation and purification of the often thermally labile and light sensitive anhydrides 3L61. Once prepared, the radical precursors 3 can be smoothly cleaved to give their product radicals, simply by heating ( T = SOOC) or by photolyzing in inert solvents with an incandescent light bulb, in the presence of suitable radical traps.For the application of N-alkoxypyridinethiones 2 as sources of alkoxyl radicals, an additional isolation step has been necessary in order to remove sideproducts from the synthesis of 2 which would otherwise interfere with the subsequent radical rea~tion[~,'*~1. In the course of our studies on alkoxyl radicals as intermediates in the stereoselective synthesis of tetrahydrofurans, we prepared several esters 2 and were interested in a detailed analysis of the structural and spectroscopic properties of our radical precursors, especially from X-ray crystallography and NMR [NOE and (C,H) COSY experiments]. Furthermore, differential scanning calorimetry (DSC) experiments were carried out to get some appraisal of the thermal stability of the esters 2, which have hitherto simply been described as thermally We were surprised to notice that the well-known O-acylpyridinethiones 3 -the Barton anhydrides['] -as well as the corresponding oxygen derivatives, the pyridones 7 and ti[''], had not to our knowledge, been subjected to such studies previously.Results and Discussion N-Alkoxypyridine-2( 1 H)-thiones (2) were prepared from 1 -hydroxypyridine-2( 1 fQ-thione (1) via its tetraethylammonium salt[s] and the appropriate alkyl halides" 'I. The reaction of cis-4-tert-butylcyclohexyl bromide[l21 and 2-mercaptopyridine N-oxide tetraethylammonium sal...