John N. Gitua

Mechanistic Comparison of the Nickel(0)‐Catalyzed Homo‐Oligomerization and Co‐Oligomerization of Alkynes and Nitriles

A comparative mechanistic study of the nickel(0)-catalyzed homo-oligomerization and co-oligomerization of alkynes and of nitriles has been undertaken, with diphenylacetylene and benzonitrile, towards an array of nickel(0) reagents, such as finely divided nickel, (COD)2Ni, (Bpy)(COD)Ni, (Et3P)4Ni, (Bpy)(PhC≡CPh)Ni and (COD)2Ni−MeAlCl2 combinations in donor (THF) and nondonor (PhMe or neat substrate) solvents. Special attention has been given to the detailed molecular structures of the initial 1:1 adducts, (Bpy)(PhC≡CPh)Ni, (Ph3P)3(PhC≡CPh)Ni and [(Ph3P)(PhC≡N)Ni]4 by a consideration of XRD and IR data. Data from the single crystal XRD analysis of (Bpy)(PhC≡CPh)Ni, reported here for the first time, are shown to be in excellent accord with the presence of a 2,3-diphenylnickelacyclopropene ring for the (PhC≡CPh)Ni moiety with almost coplanar chelating coordination of the bipyridyl ligand, rather than with the presence of simple “side-on” coordination of the alkyne with the metal center. A parallel analysis of XRD and IR data for the two benzonitrile-nickel(0) complexes, which were drawn from previous publications, has concluded that the nickel in (Ph3P)3(PhC≡N)Ni is coordinated in an “end-on” fashion and the nickel centers in [(Ph3P)(PhC≡N)Ni]4 are coordinated as bridges between nitrile units in both an “end-on” and “side-on” manner. The stereochemistry of the acid hydrolysis of the nickelacyclopropene complex to (E)- or (Z)-alkene was shown to depend on the structure of the cleaving acid; parallel hydrolysis of nitrile-nickel complexes has shown that “end-on” complexes regenerate the nitrile, while “side-on” complexes lead to the aldehyde. In homo-oligomerization of diphenylacetylene or other alkyne the clean cyclotrimerization to the benzene derivative was shown to proceed by way of a nickelacyclopentadiene intermediate, as was evident by chemical trapping. The homo-oligomerization of benzonitrile by nickel(0) was found not to lead to 2,4,6-triphenyl-1,3,5-triazine, as claimed in the literature, but rather solely to benzyl phenyl ketone, the dimeric hydrolysis product. The attempted co-oligomerization of diphenylacetylene and benzonitrile with ordinary nickel(0) complexes led only to the homocyclotrimer of the alkyne. Only when the alkyne was prebonded to the nickel, as in (Bpy)(PhC≡N)Ni, could significant amounts of a codimerization product with the nitrile be observed. The origin of the triazine, claimed in a previous report to form from benzonitrile and Raney nickel, has been traced to the presence of adventitious moisture and air. Other unexpected products formed from nickel(0) complexes and benzonitrile have been shown to arise from oxidative addition reactions of nickel(0) with various σ C−E bonds.

Expanding the scope of medical mission volunteer groups to include a research component

BackgroundServing on volunteer groups undertaking medical mission trips is a common activity for health care professionals and students. Although volunteers hope such work will assist underserved populations, medical mission groups have been criticized for not providing sustainable health services that focus on underlying health problems. As members of a volunteer medical mission group, we performed a bed net indicator study in rural Mali. We undertook this project to demonstrate that volunteers are capable of undertaking small-scale research, the results of which offer locally relevant results useful for disease prevention programs. The results of such projects are potentially sustainable beyond the duration of a mission trip.MethodsVolunteers with Medicine for Mali interviewed 108 households in Nana Kenieba, Mali during a routine two-week medical mission trip. Interviewees were asked structured questions about family demographics, use of insecticide treated bed nets the previous evening, as well as about benefits of net use and knowledge of malaria. Survey results were analyzed using logistic regression.ResultsWe found that 43.7% of households had any family member sleep under a bed net the previous evening. Eighty seven percent of households owned at least one ITN and the average household owned 1.95 nets. The regression model showed that paying for a net was significantly correlated with its use, while low perceived mosquito density, obtaining the net from the public sector and more than four years of education in the male head of the household were negatively correlated with net use. These results differ from national Malian data and peer-reviewed studies of bed net use.ConclusionsWe completed a bed net study that provided results that were specific to our service area. Since these results were dissimilar to peer-reviewed literature and Malian national level data on bed net use, the results will be useful to develop locally specific teaching materials on malaria prevention. This preventive focus is potentially more sustainable than clinical services for malaria treatment. Although we were not able to demonstrate that our work is sustainable, our study shows that volunteer groups are capable of undertaking research that is relevant to their service area.

Quality and stability of artemether-lumefantrine stored under ambient conditions in rural Mali.

BackgroundThe quality and stability of anti-malarial drugs in the Global South has long been of significant concern. Drug quality can be affected by poor or fraudulent manufacturing processes, while drug stability is affected by temperature and humidity. Knowledge of drug quality and stability is often the unique contribution of pharmacists volunteering on short-term medical mission trips.ObjectiveTo determine the quality and stability of artemether-lumefantrine 20/120 mg under ambient storage conditions in rural Mali.MethodsOne unopened blister pack of artemether-lumefantrine 20/120 mg (IPCA Laboratories, Mumbai) was stored under ambient conditions in a warehouse in a Malian village for one year. A second pack from the same lot number was stored under temperature and humidity controlled conditions in a university laboratory. The active ingredients of tablets from both packages were analysed using thin layer chromatography, nuclear magnetic resonance and infrared spectroscopy. The IPCA samples were referenced for drug identity and content to an identical American made product (Coartem ®, Novartis Pharmaceuticals).ResultsThin layer chromatographs, nuclear magnetic resonance and infrared spectroscopy results were identical for both IPCA samples and the reference product.ConclusionsThe IPCA products contained the same drugs in the same amount as on their package label and were identical to the reference product. It is concluded that they were of good quality. Spectroscopy results demonstrate the sample stored in Mali was stable for one year. Pharmacists volunteering on medical mission trips may dispense this product with confidence. At the end of a mission trip, pharmacists may store left over artemether-lumefantrine under ambient conditions for up to one year without concern for significant degradation of the active ingredients.

ErratumErratum to “Carbon–carbon bond formation via oxidative-addition processes of titanium(II) reagents with π-bonded organic substrates. Reactivity modifications by Lewis acids and Lewis bases. Part 22. Organic chemistry of subvalent transition metal complexes: [Journal of Organometallic Chemistry 624 (2001) 229–238]

Abstract A series of titanium(II) derivatives, TiE 2 , was prepared by alkylative reduction of TiE 4 by two equivalents of n -butyllithium in THF at −78 to 25°C (E=Cl, F, OBu n , OPr i and 0.5 NPh–CH 2 –CH 2 –NPh). The LiE by-product could usually be removed by THF evaporation and dissolution of the TiE 2 into toluene. All such TiE 2 derivatives were shown to effect the epimetallation and oligomerization of olefins, acetylenes and carbonyl derivatives in varying degrees. Particularly pertinent were the isolation and chemical reactions of titanium(II) isoproxide, the postulated intermediate in the Kulinkovich synthesis of cyclopropanols from ethyl Grignard reagents and organic esters, as well as an intermediate in many allied reactions developed by the Sato group. The findings of the present study corroborate completely the foregoing hypothesis that titanium(II) isopropoxide is the key intermediate in such novel reactions in organic synthesis. Furthermore, Ti(OPr i ) 2 can be prepared readily in a relatively pure state and has been found to react with 1-alkenes, alkynes and ketones by epimetallation at 25°C to form three-membered titanacycles, which can be utilized in organic synthesis. Finally, the ease with which such TiE 2 derivatives epimetallate unsaturated organic substrates has been shown to be decreased by the steric demands of E and by the coordination of Lewis bases or donor solvent to the titanium(II) center. Lewis acids, on the other hand, greatly increase the rate of epimetallation by TiE 2 . A dramatic illustration of this effect is in the action of TiCl 2 ·Me 2 AlCl on unsaturated hydrocarbons, wherein the polymerization of ethylene and of 1-alkene and the cyclotrimerization of alkynes are found to occur at room temperature.