Pyrolysis of α- and β-Heteroatoms Substituted Ethyl Phenyl Sulfoxides

Abstract

A study on the mechanism of the thermal decomposition of α-and β-heteroatoms substituted ethyl phenyl sulfoxides was carried out using 1-chloroethyl phenyl sulfoxide (1); two diastereomeric 1-acetoxyethyl (substituted phenyl) sulfoxides (2a) and (2b); and 2-chloroethyl phenyl, 2-bromoethyl phenyl, and 2-methoxyethyl phenyl sulfoxides (3, 4, 5). The rate of pyrolysis of 1 was 4.8 times faster at 160 • C than that of ethyl phenyl sulfoxide used as a reference, while those of 2a and 2b were 107 and 155 times faster, respectively. The results indicate that the lone pair of electrons on the α-heteroatoms has a larger rate acceleration effect than the electronegativity of them. The substituent effects of the phenyl group of 2a and 2b gave positive Hammett ρ-values (ρ a = 0.76 and ρ b = 0.80 vs. σ ). Activation parameters for 2a and 2b are as follows: 2a, H ‡ = 112 kJmol −1 , S ‡ = −20 JK −1 mol −1 ; 2b, H ‡ = 107 kJmol −1 , S ‡ = −29 JK-1mol −1 .Large deuterium kinetic isotope effects for 1-acetoxyethyl-2,2,2-d 3 phenyl sulfoxides (2ad and 2bd) were observed (k H /k D = 3.5 ∼ 4.1). These results suggest that the pyrolysis of α-heteroatom substituted ethyl phenyl sulfoxides proceeds via a five-membered transition state deviated to E1-like in character. On the other hand, from the results of kinetics for the pyrolysis of 3, 4, and 5, no effect by the β-halogen atoms or some deceleration effect by the β-methoxy group was observed. Thus the reaction seems to proceed via an E1-like mechanism.

Rapid Photoracemization of Chiral Alkyl Aryl Sulfoxides

“…In addition to methyl phenyl sulfoxide ( 1b ), − aromatic moieties containing various functional groups were tolerated ( 1c , − 1d , 1e , ,, 1f , , 1g , 1h , 1i , 1j ,). Additionally, alkyl groups attached to the sulfur atom ( 1k , , 1l ) and functionalized alkyl ( 1m , 1n , 1o , 1p , 1q , 1r ,), tolyl ( 1s ), and vinyl ( 1t ) groups were also rapidly racemized. Investigation of the reaction scope revealed that various substitution patterns were tolerated and every racemization reaction proceeded extremely fast ( k 2 = 1.77 × 10 4 –6.08 × 10 1 M –1 s –1 , t 1/2 = 0.4–114 s).…”

Synthesis and drug development of small molecule inhibitors of PTP1B

“…An overview of final wave of benzodioxane based upon compound 30a, is summarised in Scheme 33 132,145,148,153,[161][162][163][164][165] where the key aim of this compound library was with improving potency and selectivity towards PTP1B.…”

“…Adapted from a known procedure. 162 A solution of compound 30a (2.01 g, 8.5 mmol, 1.0 equiv.) in anhydrous diethyl ether (20 mL) was added dropwise to a stirred suspension of LiAlH4 (759 mg, 20.0 mmol, 2.0 equiv.)…”

“…s, H6β), 3.6 (2H, s, H5), 3.7 (1H, s, H9), 4.2 (2H, q, J 7.0 Hz, H12β), 4.3 (2H, app t, J 6.2 Hz, H12α), 6.7 (1H, s, NH), 7.27 (1H, m, H1), 7.32 (4H, app d, H2 & H3). 13 C NMR (CDCl3); δ 14.18 (C13α), 14.23 (C13β), 31.7 (C7x), 36.9 (C7y), 49.5 (C6x), 50.2 (C6y), 58.1 (C10), 61.2 (C12α), 61.3 (C12β), 62.7 (C5), 68.2 (C8), 127.4 (C1), 128.4 (C2), 129.2 (C3), 137.3 (C4), 139.4 (C9), 162.2 (C11α), 168.4 (C11β). Rf 0.176 (30% EtOAc/hexanes).…”