94210-44-3Relevant academic research and scientific papers
Lessons of 3-alkoxy-4-(p-chlorophenyl)4,3-thiazole-2(3H)-thione chemistry learned from structural investigations
Hartung, Jens,Daniel, Kristina,Bergstraesser, Uwe,Kempter, Irina,Schneiders, Nina,Danner, Steffen,Schmidt, Philipp,Svoboda, Ingrid,Fuess, Hartmut
, p. 4135 - 4142 (2009)
Synthetic, spectroscopic, and structural investigations provided evidence that distinguished neat 3-alkoxy-4-(p-chlorophenyl)-l,3-thiazole-2(3H)-thiones (CPTTORs), once developed to serve as alkoxyl radical precursors for storage and use on demand, showed
N-hydroxy-4-(4-chlorophenyl)thiazole-2(3H)-thione as a photochemical hydroxyl-radical source: Photochemistry and oxidative damage of DNA (strand breaks) and 2′-deoxyguanosine (8-oxodG formation)
Adam, Waldemar,Hartung, Jens,Okamoto, Hideki,Saha-Moeller, Chantu R.,Spehar, Kristina
, p. 619 - 624 (2007/10/03)
On irradiation of N-hydroxythiazole-2(3H)-thione 3 at 300 nm, the photoproducts disulfide 4, bisthiazole 5 and thiazole 6 are formed. During this photolysis, hydroxyl radicals are released, which have been detected by spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), coupled with electron paramagnetic resonance spectroscopy. In the presence of supercoiled pBR322 DNA, irradiation of thiazolethione 3 induces strand breaks through the photogenerated hydroxyl-radicals, as confirmed by control experiment with the hydroxyl-radical scavenger isopropanol. Singlet oxygen appears not to be involved, as attested by the lack of a D2O isotope effect. During the photoreaction of thiazolethione 3 in the presence of 2′-deoxyguanosine (dG), the latter is photooxidized (ca 10% conversion after 2 h of irradiation) to the 7,8-dihydro-8-oxo-2′-deoxyguanosine as the main oxidation product. The dG conversion levels off after complete consumption of thiazolethione 3 and is suppressed by the addition of the hydroxyl-radical scavenger 2,6-di-tert-butylcresol or DMPO. Since the photoproducts 4-6 are ineffective as sensitizers for the photooxidation of dG and DNA, the hydroxyl radicals released in the photolysis of thiazolethione 3 are the oxidizing species of DNA and dG. These results suggest that the thiazolethione 3 may serve as a novel and effective photochemical hydroxyl-radical source for photobiological studies.
A new generation of alkoxyl radical precursors - Preparation and properties of N-(alkoxy)-4-arylthiazole-2(3H)-thiones
Hartung, Jens,Schwarz, Michaela,Svoboda, Ingrid,Fuess, Hartmut,Duarte, Maria Teresa
, p. 1275 - 1290 (2007/10/03)
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) A] and long N-O connectivities [N3-O1 = 1.369(3)-1.379(2) A] 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 10 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.
