Study of geometric and electronic effects on sulfoxide electrophilic sulfenylation (SES)

Intramolecular Sulfoxide Electrophilic Sulfenylation (SES) has been extensively employed to synthesize fused N,S-bridged heterocycles. Typical conditions are either thermal or electrophilic agent activation.; The sulfoxide, 4-chloro-6-methylsulfinyl-5-(1-pyrrolyl)pyrimidine ( 1), was synthesized in good yield. Reaction under typical SES reaction conditions, which employs trifluoroacetic anhydride (TFAA) in dimethylformamide (DMF) at 0° to room temperature, unexpectedly gave pyrrolinone 2 as the major product in addition to the normal SES product. This is the first time that a pyrrolinone was found in a SES reaction, in which a pyrrole ring is oxidized by a sulfoxide group. It has been proven that the key step of pyrrolinone formation is the protonation of pyrrole ring. Steric crowding around the pyrrole ring promotes the deviation of the reaction pathway from SES to oxidation. Results presented in this thesis work indicated that the bulky substituents of spacers between the sulfoxide and the pyrrole ring cause distortion of the molecules. The pyrrole ring was forced out of the molecular plane to minimize potential energy. This increased the basicity of the pyrrole by eliminating interannular conjugation, thereby increasing the ease of protonation of the pyrrole, which led to the formation of the pyrrolinones. Departure of pyrrole from the molecular plane aids in the pyrrolinone formation by limiting the competitive SES reaction due to the large distance from the sulfur atom to the C-2 atom of the pyrrole. Electronic factors of pyrimidine ring also enhance oxidation.; Six more target sulfoxides were successfully prepared for investigation. Three sterically crowded sulfoxides, 2,4-dimethyl-5-methylsulfinyl-6-(1-pyrrolyl)pyrimidine (4), 4-methyl-2-methylsulfinyl-3-(1-pyrrolyl)pyridine ( 6), N-(2-chloro-6-methylsufinylphenyl)pyrrole (8) and a non-sterically crowded pyrimidine-containing sulfoxide, 4-methylsulfinyl-3-(1-pyrrolyl)pyrimidine (5), also gave the novel pyrrolinones under the same reaction conditions, as well as the normal SES products (fused N,S-heterocycles). The formation of pyrrolinones under SES conditions has potential to be a novel method of pyrrole functionalization. Two non-sterically crowded sulfoxides, 2-methylsulfinyl-3-(1-pyrrolyl)pyridine (7) and N-(2-methylsulfinylphenyl)pyrrole (9), produced only the normal SES products in excellent yields.; Three different calculation methods of molecular modeling using HyperChem (5.1) were applied in this thesis work. The results presented provide the good support for the experimental data. The fact that sterically crowded sulfoxides have larger torsion angle and longer C-S distance supports the production ratio of oxidation vs. SES. The atomic charges calculated prove that pyrimidine derivatives are faster in oxidation and slower in SES.