Thiiranes, nucleophilic substitution

Intramolecular nucleophilic substitution to form thiiranes was studied by means of ab initio MO computations based on the 6-31G basis set <1997JCC1773>. Systems studied included the anions SCH2CH2F and CH2C(=S)CH2F which would afford thiirane and 2-methylenethiirane, respectively (Equations Z and 3). It was important to include electron correlation which was done with the frozen-core approximation at the second-order Moller-Plesset perturbation level. Optimized structures were confirmed by means of vibrational frequency calculations. The main conclusions were that electron correlation is important in lowering AG and AG°, that the displacements are enthalpy controlled, and that reaction energies are strongly dependent on reactant stabilities. 

A very attractive synthesis of fused-ring thiiranes based on nucleophilic substitution-elimination was demonstrated by Yadav and Kapoor <2002S2344>. The procedure involves treatment of 2-chloro- or 2-bromocyclohexanone with (EtO)2P(S)SH and NaBH4-alumina (Scheme 67). Upon microwave irradiation of this solvent-free mixture, the nucleophilic replacement and subsequent reductive cyclization gave rise to thiiranes in good yield. 

The mechanism of the Ramberg-Backlund reaction is rather straightforward. When a-halosulfone 1 is treated with a strong base, deprotonation rapidly takes place to give a-anion 3, which undergoes a backside displacement (intramolecular nucleophilic substitution, SNi) to provide thiirane dioxide 4 (also known as episulfone) as the key intermediate.10 The Swi reaction with loss of halide is the rate-limiting step. Finally, the unstable 4 releases sulfur dioxide and the ring strain to deliver alkene 2. 

The acid-catalyzed additions of bromide and chloride ion to thiiranes occurs readily, with halide preferentially but not exclusively attacking the most substituted carbon atom of the thiirane. The reaction of 1-substituted thiiranes with acetyl chloride shows a slight preference for halide attack at the less substituted carbon atom (80MI50601). For further discussion of electrophilic catalysis of halide ion attack see Section 5.06.3.3.2. The reaction of halogens with thiiranes involves electrophilic attack on sulfur (Section 5.06.3.3.6) followed by nucleophilic attack of halide ion on carbon. 

Similarly, the reaction of the parent thiirane dioxide, the 2-chloro- and 2,3-cis-dimethylthiirane dioxides with either Grignard or alkyl lithium reagents, has been studied extensively. The fair-to-good yields of the sulfinates (62) obtained (48-82%), accompanied by ethylene (or the corresponding alkenes for substituted thiirane dioxide), have been interpreted in terms of initial nucleophilic attack of the base on the sulfur atom as depicted in equation 17116. 

Sulfur atom as internal nucleophile. In this area, it has been shown that the reaction of 8-bromo-l,3-dimethyl-7-(2,3-epithiopropyl)xanthine 147 with a range of aliphatic and aromatic amines generates efficiently 2-amino-substituted 2,3-dihydro-thiazolo[2,3-/]xanthine derivatives 148. The process involves a sequential amine-induced thiirane ring opening followed by thiolate z/MYi-substitution of chlorine atom (Equation 66) <1994PCJ647>. 

The effect of different heteroatoms on the ring opening of substituted three-membered rings was investigated at the B3LYP/TZV+P level of theory.115 Two specific water molecules were included in the calculations and the COSMO method was used to include the bulk solvent. With the methyl thiolate nucleophile, thiirane was... 

Nucleophilic attack at sulfur of thiirane, thiirane-l-oxide, and thiirane-l,Tdioxide is to be expected, as such attacks (substitutions) relieve ring strain if attack is concerted with ring opening. 

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