Reactions of Bis(oxy)enamines with Transition Metal Halides
Synthesis of halooximes has attracted much attention given their importance as precursors to proline derivatives1, unnatural amino acids2 and a host of alkaloids3. Halooximes have numerous industrial and biological applications 4, for example oxime ethers increases specific channel opening activities, acting as potential targets in drug treatment for various diseases 5, most adrenergic β-receptor blocking compounds also conform to the structure of oxime ethers 6. They also have vitro antifungal activities against certain plants7. A known method for the synthesis of 3 using Me3SiX as a Lewis acid, via intermediate enamines with acyclic/ cyclic bis(oxy)enamines, gives yields between 21-68%. Low yield stems from lack of reaction specificity2. In this work, we investigate coupling nitrogen-oxides with CoBr2 to synthesise halooximes in high yield. Initial cyclic/ acyclic bis(oxy)enamines were prepared by reacting 1 equiv. nitro compound with 2.4 equiv. in excess of dichloromethane under argon atmosphere at a temperature of 0ºC. 2.2 equiv. of TMS-Br was further added and left to stir till thermal equilibrium with room conditions. The cyclic/ acyclic bis(oxy)enamine was isolated upon aqueous work-up, filtration and evaporation. Synthesis of halooximes was carried out by reacting 8mL to 1mmol equiv. of THF and 2 equiv. of CoBr2 under argon atmosphere and left to stir till CoBr2 dissolves. 2mL to 1mmol equiv. of CH2Cl2 was added to 1 equiv. of bis(oxy)enamines. The reaction mixture was left to stir at room temperature for 2 hours, after which aqueous work-up, filtration and evaporation were carried out. Our results are summarized in Table 1. We also obtained relatively high percentage yields for the direct synthesis of bromooximes from cyclic nitronates via a one-pot procedure: Low yield stems from lack of reaction specificity2. In this work, we investigate coupling nitrogen-oxides with CoBr2 to synthesise halooximes in high yield. Initial cyclic/ acyclic bis(oxy)enamines were prepared by reacting 1 equiv. nitro compound with 2.4 equiv. in excess of dichloromethane under argon atmosphere at a temperature of 0ºC. 2.2 equiv. of TMS-Br was further added and left to stir till thermal equilibrium with room conditions. The cyclic/ acyclic bis(oxy)enamine was isolated upon aqueous work-up, filtration and evaporation. Synthesis of halooximes was carried out by reacting 8mL to 1mmol equiv. of THF and 2 equiv. of CoBr2 under argon atmosphere and left to stir till CoBr2 dissolves. 2mL to 1mmol equiv. of CH2Cl2 was added to 1 equiv. of bis(oxy)enamines. The reaction mixture was left to stir at room temperature for 2 hours, after which aqueous work-up, filtration and evaporation were carried out. Our results are summarized in Table 1. We also obtained relatively high percentage yields for the direct synthesis of bromooximes from cyclic nitronates via a one-pot procedure:
Ancient Medicine- Modern Approach
The apricot kernel is believed to have a great medicinal value in many cultures. However, literature and research indicates that this belief still remains extremely controversial and conclusions regarding the medicinal value are ambiguous due to the presence of cyanide in the kernel. The focus of this research was to evaluate two objectives through the use of several integrated technologies and modified methods: (a) To successfully remove the cyanide from the apricot kernel using an adapted method; (b) To determine the effects of the cyanide free apricot kernel extracts on Helicobacter pylori and Streptococcus pyogenes bacteria. Procedures The apricot kernels were removed from the pits and then ground using a food processor. The kernels were then tested for cyanide using a cyanide test kit and Cyantesmo test tape. These tests indicated that cyanide was present. A novel approach was devised to remove the cyanide and when retested, the kernels tested negative for cyanide. This result was confirmed with Infrared Spectroscopy. The cyanide free kernels were then extracted using a Soxhlet Extractor with methanol for 24 hours. In addition to the methanol extraction, three other techniques were used to obtain kernel extracts: (a) Celite filtration, (b) Infusion Method A, (c) Infusion Method B. The Kirby Bauer method was modified for the microbiology aspect of this project. The Helicobacter pylori and Streptococcus pyogenes bacteria were plated using a 0.5 McFarland Standard. Paper filter discs containing 20µL of each extract were placed onto the inoculated plates in replicates of nine. After 48 hours of incubation, the zones of inhibition were read for each plate. Data The results were extremely encouraging and therefore to ensure the accuracy and preciseness of the data collected, four statistical analyses were completed. These include Confidence Intervals (CI), Standard Deviation (STDEV), T-Tests, and Chi Tests. The methanol extract was significantly different from the control in all trials. The Chi test also yielded a Chi Square value of 223, which was significantly greater than the critical value of 15.507, indicating that the results observed were not due to coincidence. Conclusion Literature evidence has indicated that the apricot kernel has been and is still used for medicinal purposes. Studies have shown that the presence of cyanide and the risks associated with this compound outweigh any benefits gained from the kernel. It has also been suggested that previous bacterial testing resulting in positive inhibition may have been due to the presence of cyanide. However, in this study, I was able to remove the cyanide through an innovative method to prove that the biological activity observed was highly unlikely to be due to cyanide. This indicates that there are other compound(s) in the apricot kernel that have specific antibacterial properties. The potential to improve the quality of life through the application of the apricot kernel appears to be supported, and further studies justified at this time.