Efficiency of alkoxyl radical product formation from 5-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones

Tertiary alkoxyl radicals from 3-alkoxythiazole-2(3H)-thiones

“…The thiohydroxamic acid we chose in this study, 3-hydroxy-5-(4-methoxyphenyl)-4-methylthiazole-2(3H)-thione (MAnTTOH; 2), has a remarkable affinitity for substitution at oxygen instead of sulfur, if treated with an appropriate carbon electrophile. 17 To develop a synthetic method (1a, 1b; Section 2.1), investigate thermal stability (1d; Section 2.2), perform intramolecular reactions (1c, 1f; Section 2.3 And 2.4), and explore intermolecular alkoxyl radical additions (1a, 1dee; Section 2.5), we selected tert-alcohols 3aef as substrates to in situ generate carbon electrophiles.…”

“…We now report that slow addition of 5.5 equiv of the alkylation reagent to a CH 2 Cl 2 -solution of thiohydroxamic acid at 24 C furnishes O-tert-butyl ester 1a in 58e64% yield, besides S-tert-butyl derivative 4a (25%). 17,19,32 A change in solvent to DMF, fewer O-tert-butyl isourea equivalents, or lower reaction temperature ( 0 C) reduces the yield of tert-butyl ester 1a. Higher rates of O-tert-butyl isourea addition lead to formation of 1,2-bis-[5-(4-methoxyphenyl)-4-methylthiaz-3-yl]-disulfane (5) 33 as additional product in up to 13% yield, whereas the yield of product 1a decreases.…”

“…For both modes of activation C 6 H 6 or C 6 H 5 CF 3 are useful solvents, and BrCCl 3 the preferred mediator for conducting synthetic and mechanistic investigations. 17 Photolysis of 3-(2-methyl-5-phenylpent-2-oxy)-thiazolethione 1c and BrCCl 3 (c 0 ¼1.70 M) in a solution of C 6 D 6 furnishes alcohol 3c (36%), d-bromohydrin 9 (41%), tetrahydrofuran 10 (22%), disulfide 5 (20%), and 5-(4-methoxyphenyl)-4-methyl-2-trichloromethylsulfanyl thiazole (11) (10%). Acetone (12) is obtained in 3e5% yield.…”

“…14e16 In an earlier study, we had shown that 3-alkoxy-5-(4-methoxyphenyl)-4-methylthiazole-2(3H)-thiones (e.g., 1) almost quantitatively liberate alkoxyl radicals, if thermally or photochemically activated in the presence of a mediator. 17 Primary and secondary 3-alkoxy-5-(4-methoxyphenyl)-4-methylthiazole-2 (3H)-thiones are synthetically available in yields between 70 and 90%. 17 Fig.…”

“…17 Primary and secondary 3-alkoxy-5-(4-methoxyphenyl)-4-methylthiazole-2 (3H)-thiones are synthetically available in yields between 70 and 90%. 17 Fig. 1; R¼alkyl or phenyl (vide infra); nomenclature: A¼associative step, S¼substitution, D¼dissociative step, R¼radical-based transformation].…”