Photobromination of (+)-camphene and efficient synthesis of novel camphene based compounds through suitable reactions

(1S,4R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane (2) is an isomer of naturally occurring mono-terpene called camphene 1 which has high therapeutic and medicinal values as potential lipid lowering agent. It is a potential candidate for cardiovascular diseases as well as their derivatives showing significant bioactive properties like anti-viral, anti-tuberculosis, anti-oxidant, anti-bacterial and anti-fungal activities. The bicyclic skeleton of (+)-camphene (2) is used to form rearrangement products via bromination reactions which are toxic, though non-rearrangement derivatives of (+)-camphene 2 are biologically active. In this thesis, the ring regulation tendency of bicyclic structure of (+)-camphene (2) was inhibited by suitable method, besides, high yield of non-rearrangement mono-brominated compounds were produced by the repair of bicyclic skeleton via repeated Wagner-Meerwein rearrangement and synthesized considerable amounts of non-rearrangement optically active chiral compounds from mono-brominated (+)-camphene 277. Additionally, rearrangement mono-brominated compound 279, di-brominated compound 276 and tri-brominated compounds 280-284 were synthesized from rearrangement compounds with different reaction conditions. In this study, the high temperature bromination of (+)-camphene (2) was carried out in presence of different light intensity and the mixture of non-rearrangement compounds 274 and 275 was obtained at 650 watt of light in presence of molecular bromine and CCl4 as a solvent. Compounds 274 and 275 were completely transformed into rearrangement compound 276 via Wagner-Meerwein rearrangement in presence of SiO2 in the purification process. Compound 276 was treated with t-BuOK in presence of THF at reflux temperature and mono-bromo bornene 279 was obtained which was treated with molecular bromine at low (0°C) and high (77°C) temperature and compounds 280 and 281-284 were synthesized respectively. Additionally, compound 279 was treated again with t-BuOK in presence of sodium metal and compound 286 was obtained. Compound 276 was treated with aniline for the reconstruction of the structure of (+)-camphene (2) at reflux temperature and high yield (86%) mono-brominated compound 277 was synthesized with small amount (14%) of compound 278. Compound 277 was treated with molecular bromine at very low temperature (-15°C) and rearrangement compound 285 was obtained. Furthermore, Suzuki-Miyaura coupling reaction of compound (1S,4R,E)-3-(bromomethylene)-2,2-dimethylbicyclo-[2.2.1]heptane (277) was carried out with five different boronic acid compounds in presence of [Pd(PPh3)]4 and non-rearrangement compounds 288, 290, 292, 294 and 296 were synthesized. Nucleophilic substitution reaction of compound 277 was performed and non-rearrangement compounds 297 and 298 were synthesized in presence of NaOCH3 and CuCN respectively. The structure of all synthesized compounds was determined by the 1H NMR, 13C NMR, FTIR and a few of them were characterized also by 19F NMR, COSY NMR, X Ray crystallography for addressing the exact structural skeleton. The polarimetry analysis of all the synthesized compounds was performed with polarimeter for their optical activity to distinguish the isomers. The coupling constant, shielding and de-shielding effects were discussed for addressing the connection of the substituent groups to the structural skeleton.