Some heterocyclic systems as ambident electrophiles.
thesisposted on 19.11.2015, 08:47 by John. Suschitzky
Some heterocyclic systems were investigated for ambident electrophilic behaviour. Of the cases reported in the literature, the majority involve nucleophilic attack, most frequently by cyanide on a halomethyl aromatic system to give as the major product, the expected cyanomethyl compound ('normal' product) accompanied by the compound derived from SNl' or SN2' attack of cyanide ('abnormal' product). In the present work, the halomethyl derivatives of the following systems were investigated: benzothiophene, thiophene, benzofuran, furan, and pyrazine. Triphenyl- methylchloride was also investigated for comparison. The ability of these systems to display ambident electrophilic behaviour is correlated with their structure. Solvent effects are also investigated. 2-Furfuryl was taken as a model system because of its great tendency to give abnormal products. The system was made to rearrange under conditions in which the temperature and the nature of the nucleophile and leaving group were varied. The competition between 'normal' and 'abnormal' product formation appears to be kinetically controlled. The interesting transformation of 2-bromomethyl-5-methylthiophene to 3-bromo-2, 5-dimethylthiophene has been reported to occur. A detailed examination of this reaction was undertaken and the mechanism is discussed. At the end of the Thesis, a report of the work completed in industry* as part of the CAPS scheme is given. The objective of this work was to examine synthetic procedures for obtaining the enantiomers of 4(5)-(2-aminopropyl) imidazole (? -methylhistamine) and 4(5)-(2-amino-l-methylethyl)imidazole (B -methylhist-amine) in order to provide new compounds for biological testing. A new synthesis of ? -methylhistamine from L-histidinol has been devised; the optical purity of the product is unknown. B -Methylhistamine has been obtained in quantity and has been partially resolved with D-camphor-10-sulphonic acid. An unsuccessful attempt to prepare 4 (5) - (2-amino- 1-methylethyl)-2-methylimidazole by a method which has been used for 4(5)-(2-aminoethyl)-2-methylimidazole (2-methylhistamine) is also described.