Kurzfassung

Abstract:
Bond angles at thiohydroxamate oxygen in crystal structures of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones gradually increased with the size of the 3-alkoxy substituent. This effect was attributed to strain on the basis of (i) a linear free energy relationship (Taft-Dubois correlation) and (ii) signal coalescence from resonances of diastereotopic CH3 groups in solution (O-cumyl substituent; DNMR). Substitution at oxygen along the sequence OR (R = prim, sec, and...Abstract:
Bond angles at thiohydroxamate oxygen in crystal structures of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones gradually increased with the size of the 3-alkoxy substituent. This effect was attributed to strain on the basis of (i) a linear free energy relationship (Taft-Dubois correlation) and (ii) signal coalescence from resonances of diastereotopic CH3 groups in solution (O-cumyl substituent; DNMR). Substitution at oxygen along the sequence OR (R = prim, sec, and tert-alkyl), OH, and OLi was reflected in a gradual decrease of N,O distances and lengthening of associated C,S bonds. The responsivity for these changes was more pronounced in the thiazole-2(3H)-thione- than in the pyridine-2(1H)-thione series.

Conclusions:
The pursuit of structural chemistry in the series of N-alkoxy-5-(p-methoxyphenyl)-4-methylthiazolethiones, the underlying thiohydroxamic acid, the derived lithium salt, and its pyridinethione congeners provided three distinctive results.
(i) Bond angles at thiohydroxamate oxygen gradually increased along the series of substituents CH3 via primary alkyl, secondary alkyl to tertiary alkyl. The magnitude of angle widening correlated with Taft-Dubois parameter of associated ester substituents thus pointing to strain as major effect.
(ii) In a set of N-hydroxy-, N-alkoxy- and N-benzoyloxy-substituted compounds and lithium salt, N,O and C,S bond lengths were inversely correlated. The stronger gradient of underlying N,O/C,S-relationships upon substitution at exocyclic oxygen pointed to a stronger of N-oxy-substituted thiazole-2(3H)-thiones upon substitution at oxygen than in the pyridine-2(1H)-thione series. This aspect is considered to facilitate O-alkylation with sterically demanding, e.g., tertiary substitutents in thiazole-2(3H)-derived thiohydroxamates.
(iii) Exocyclic C,S-bonds in lithium salts of a N-hydroxythiazole-2(3H)-thione and N-hydroxypyridine-2(1H)-thione differed notably length, being in favor for a thione group in the former and a sulfanyl entity in the latter case. If interpreted in terms of charge distribution, this picture correlated with the unusual O-selectivity in alkylations of thiazolethione-derived thiohydroxamate salts.
The results outlined in the present study are expected to guide reagent selection, particularly for the synthesis of tertiary thiohydroxamic acid O-esters, to serve as valuable sources of derived oxyl radicals for stimulating further developments in this area of research.

Leading References:
[1] Tertiary Alkoxyl Radicals from 3-Alkoxythiazole-2(3H)-thiones. C. Schur, N. Schneiders, U. Bergsträßer, T. Gottwald, J. Hartung, Tetrahedron 2011, DOI:10.10.16/j.tet.2010.12.071.
[2] Lessons of 3-Alkoxy-4-(p-chlorophenyl)thiazole-2(3H)-thione Learned from Structural Investigations. J. Hartung, K. Daniel, U. Bergsträsser, N. Schneiders, S. Danner, P. Schmidt, I. Svoboda, H. Fuess, Eur. J. Org. Chem. 2009, 4135–4142. DOI: 10.1002/ejoc.200900069.
[3] Aspects of Structural Thiohydroxamate Chemistry – On a Systematic in the 5-(p-Methoxyphenyl)-4-methylthiazole-2(3H)-thione Series. J. Hartung, U. Bergsträsser, K. Daniel, N. Schneiders, I. Svoboda, H. Fuess, Tetrahedron 2009, 65, 2567–2573.
[4] Hindered Rotation in N-(Acyloxy)-4-methylthiazole-2(3H)-thiones. J. Hartung S. Altermann, U. Bergsträßer, T. Gottwald, I. Kempter, C. Schur, M. Heubes, Tetrahedron, 2009, 65, 7527–7532. DOI: 10.1016/j.tet.2009.06.124.
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