A general methodology for the synthesis of pyrrolizidine alkaloids has been developed. The two key steps in the sequence were the synthesis of the dienic azide system 1 and its regioisomer 2 by utilizing the vinylogous Reformatsky reaction, and the intramolecular additions of the azide moiety across the activated dienes with subsequent pyrolyses to provide the pyrrolizidines of type 3. This study broadened the scope of the vinylogous Reformatsky reaction to include the preparation of alkaloid synthons and introduced the heteroatom equivalent of the carbenoid [4+1] annulation as a method or alkaloid synthesis. [See docment for associated image] / M.S.

Sodium borohydride reduces alkyl halides and their related tosylate derivatives in the order primary > secondary > tertiary, while the relative order of leaving-group ability is Ts⁻ ≥ I⁻ > Br⁻ > > Cl⁻. The yields obtained ranged from 90-100% for most simple, primary and secondary iodides, bromides, and tosylates, to 1-2% for the tertiary compounds. As in the case of the more reactive lithium aluminum hydride, the. reduction is believed to occur by an S_N2 displacement on carbon. The reduction of a series of para-substituted benzyl chlorides revealed that the electronic effects of groups ranging from p-methoxy to p-nitro had a rather small effect on the rate of reduction. Aryl halides arc reduced by sodium borohydride in yields dependent upon the particular halogen involved, the presence of other ortho and para electron-withdrawing substituents, and the reaction temperature, among other factors. The same relative order of dehalogenation displayed by the alkyl halides was found. Polyhalomethanes such as carbon tetrachloride react with sodium borohydride to give the monohydro and dihydro compounds as the major products, the former predominating. The exact mechanism of the reduction is as yet undetermined, as water apparently catalyzes the reaction in some unknown manner. / Master of Science

The factors determining fuse quality in hot-roll toner fixing, namely, toner and paper surface properties and machine conditions were examined. The SEM observation of the fixing states and the tape peeling test failure states showed the direct relation between the fuse quality and the toner fixing states. A physical fusing model was employed to explain the change in the shape of toner particles during the fixing process. The non-uniform fixing states were categorized into three levels. The first group comprised unmelted or only marginally melted toner particles which were weakly adhering to a paper surface and thus in a very early stage in the fusing model. The second group was composed of several combined toner particles in the middle point of the fusing model. The third group was made up of well sintered and spread toner particles called islands. These were strongly adhered to a paper surface and did not peel off by the tape test. The effect of heat and pressure on the fuse quality was to put forward the non-uniform fixing states toward the end of the fusing model giving rise to a better fuse quality. Toner surface tension measurements by a sink-float method indicated a broad distribution from 23 to 38 dyne/cm. This result was supported by ESCA data showing a clear difference in surface chemical composition of nitrogen between the high and low surface tension components of the toner. The broad range of toner surface tension could be one of the causes of the non-uniform fixing states. Paper properties, roughness and spreading also played key roles in toner fixing. The better fuse quality with the smoother paper surface was explained by a proposed model developed from paper surface roughness analysis data obtained by a traversing stylus and the knowledge of toner particle size by SEM. Differences in spreading ability of paper were responsible for observed differences in the fuse quality of paper samples at the same paper roughness. Greater spreading led to better fuse quality by obtaining more intimate contact of toner melt and paper. ESCA analyses of paper and toner surfaces suggest that spreading followed by adhesion is due to the interaction between paper and toner polar groups. / M.S.

Changes in pretreated 5182, 6061 and 7075 aluminum surfaces on exposure to moisture for short times was studied. The pretreatment used was the standard ASTM method for FPL etching of aluminum. The moisture treatment used was either immersion in water at 81° C or exposure to water vapor at 81° C. The experimental techniques used to analyze the pretreated aluminum surfaces before and after exposure to moisture were ESCA or XPS, AES, high resolution SEM, and specular reflectance FTIR. There was a change in the surface topography on exposure of the aluminum surfaces to water as determined using high resolution SEM. Stoichiometric calculations based on XPS analysis were made to estimate the amount of excess water present on the surface. Water was present on the surface before exposure to moisture, for all three alloys. The amount of water present on the surface was found to decrease with increasing times of exposure to water for all three alloys. This result was consistent with the model that pseudoboehmite formed on the surface was being converted into boehmite at longer times of exposure to water. The thickness of the oxide layer was found to increase with time of exposure to water based on ESCA results. The same conclusion was reached by depth profiling the oxide layer using AES. The rate of increase in the concentration of pseudoboehmite on the surfaces as calculated from FTIR data went in the order 7075 < 5182 < 6061. The activation energy for the third step (transport of soluble species to the surface) in the conversion of surface Al₂O₃ to AlOOH was calculated from FTIR results to be 3.5 kcal mol⁻¹. / Master of Science

Tabernaemontana johnstonii is a medium-sized tree native to Africa. Specimens of the hardwood of the plant were procured from the United States Department of Agriculture in cooperation with the cancer chemotherapy program initiated by the National Institutes of Health (NIH). An investigation was undertaken to verify that the plant possessed activity in the anti-tumor bioassay tests conducted by the NIH. Consequently, systematic fractionation of the plant in conjunction with bioassay revealed that the biological activity was concentrated in the alkaloidal portion of the plant material. Purification of the crude alkaloidal material was accomplished initially by a combination of liquid chromatography on alumina followed by buffer extraction, and subsequently, by liquid chromatography on alumina followed by liquid chromatography on silica gel. Four crystalline alkaloids were isolated during the purification procedure. Two of these alkaloids, isovoacangine and perivine, were characterized by absorption spectroscopy and mass spectrometry. Their identity was verified by comparison with authentic samples. The remaining two alkaloids were shown by nuclear magnetic resonance and mass spectrometry to be isomeric with the known bisindole alkaloid voacamine. These two alkaloids were subsequently identified as conodurine and conoduramiae, and their structural assignments were verified by comparison with authentic samples. Each of the isolated alkaloids was submitted for bioassay in the KB in vitro and the PS in vitro test. Only conodurine and conduramine showed KB activity with values of 31 g/ml and 19 g/ml respectively. All four alkaloids showed PS activity arid the following values were obtained: perivine (20 g/ml), isovoacangine (18 g/ml), conodurine (29 g/ml), and conoduraaine (20 g/ml). / Master of Science

The acidity function, H_o, of Hammett and Deyrup for a neutral basic indicator has been shown to correlate with the specific reaction rate constant, k, for a number of acid-catalyzed reactions with an A-1 mechanism. Correlations of this type have been reported for many of the strong mineral acids and certain weak acids over a wide temperature range and in aqueous, nonaqueous, or mixed solvent systems. The acid-catalyzed depolymerization of trioxane is one specific reaction which has shown relationships between rate constants and H_o in aqueous media and has been studied in the present investigation for the purpose of providing a suitable background for a study of acidity in non-aqueous media. The approach was to study the rate of depolymerization in solutions of hydrochloric acid at several temperatures and in mixtures of hydrochloric acid and various chloride salts at one particular temperature. The reaction mixtures of these solutions were prepared by mixing and diluting stock solutions of hydrochloric and trioxane (with weighed amounts of salt for salt mixtures) with water. After removal of the dissolved air, the dilatometric technique was used to determine the rate of reaction by the Guggenheim method. A set of readings, r_t, taken at times, t, and a set of readings, r_t+G, taken after allowing a fixed amount of time, G, to elapse after the first set, are related by the equation ln (r_t+G - r<sub>t</sub = - kt + constant and the slope of a plot of ln (r_t+G - r_t) against t gave the specific reaction rate constant, k, when multiplied by 2.303. The results obtained in this investigation ruay be summarized by the following statements: 1. The specific reaction rate constants (sec.⁻¹) for the decomposition of trioxane in aqueous solutions of hydrochloric acid over the temperature range of 25-60° C. can be summarized by the equation k = 3.6 x 10¹³ (h_o)^1.17_e - 28,600/RT where h_o is the value of the acidity function for hydrochloric acid. 2. The addition of a chloride salt to a reaction mixture results in an increase in the rate of reaction by an amount which is roughly in inverse proportion to the size of the cation of the salt. More exactly, the specific reaction rate constants (min⁻¹) for the decomposition of trioxane in aqueous solutions of hydrochloric acid and lithium chloride at 40° C. can be summarized by the equation log k = -1.16 H_o + 0.326 C_S 4.603 where H_o refers to the measured value of the acidity function for hydrochloric acid and C_S refers to the LiCl concentration. / Master of Science

The microwave spectrum of pentafluorosulfanylisocyanate, SF₅ -N = C = 0 has been investigated in the 8 GHz to 26 GHz region using a conventional Stark modulated spectrometer. Twenty six transitions have been assigned. A rigid rotor fit was performed by using low J transitions. The spectroscopic constants obtained are A = 2707.69 MHz, B = 1191.22 MHz, and C = 1191.13 MHz. These constants are close to those determined by the electron diffraction study on pentafluorosulfanylisocyanate and to this extent tend to support the bent -N = C = 0 structure as proposed by the electron diffraction study. / M.S.

A solution calorimeter was constructed with a temperature range of one degree in the region of 25°C. The precision of the calorimeter was about 0.3%. The heats of reaction of the following silver ethylenediamine complexes were measured: Ag(en)⁺, Ag₂(en)₂⁺⁺, Ag(en)₂⁺, and AgHen⁺⁺. With the formation constants determined by Schwarzenbach (6), the respective entropies were calculated. Enthalpy and entropy data for the Ag(en)⁺, Ag₂(en)₂⁺⁺, and Ag(en) ₂⁺ complexes are reasonable. The data for the AgHen⁺⁺ complex seems anomalous. / Master of Science

The National Cancer Institute, in conjunction with the U.S. Department of Agriculture, procured the African tree species Tabernaemontana johnstonii and found that the plant possessed anti-tumor activity in two bioassay tests. Consequently, extraction and systematic fractionation of the plant in conjunction with bioassay monitoring revealed that most of this activity was concentrated in the alkaloidal portion. Purification of active compounds was attempted by open column liquid chromatography with both alumina and silica gel supports and by thin layer and high pressure liquid chromatography on silica gel. A compound was eventually isolated and purified and it proved to be a new bis-indole alkaloid. It was given the name tabernamine and showed an activity of 1.9 μg/ml (ED₅₀) in the PS in vitro system and a T/C % of 125 at a dose of 25 mg/kg in the PS in vivo system. In conjunction with these results and the knowledge of the structure and activity levels of similar alkaloids a new bis-indole alkaloid called peribogamine was synthesized. It was conjectured that this compound would elicit a greater cytotoxic activity since it combined the apparently beneficial qualities of the others. Vobasivindoline was also synthesized since it contained the specified O-N-O triangular dimensions, a pharmacophore feature prevalent in many anti-leukemic drugs. Finally, a synthesis of 19-acetonyl voacamine was attempted as a result of the high activity of the previously isolated isomer 19-acetonyl conodurine. / Master of Science

The vacuum pyrolysis of Tl₂R¹R²C₂B₉H₉(R¹=R²=H; R¹=H, R²=CH₃; R¹R²=CH₃) species yielded some interesting thallium-containing heterocarboranes. The major pyrolysis products are thallium metal and TlR¹R²C₂B₉H₁₀. Hydrogen and the corresponding closo-carboranes, R¹R²C₂B₉H₉, were produced as minor products. The reactions of Tl₂R¹R²C₂B₉H₁₀ compounds with weak organic acids yielded the identical Tl₂R¹R²C₂B₉H₁₀ products that were produced by vacuum pyrolysis. The action of strong protic acids on Tl₂R¹R²C₂B₉H₉ produced the nido-carboranes, R¹R²C₂B₉H₉. The mechanism of the pyrolysis reaction and the proposed structures of the Tl₂R¹R²C₂B₉H₁₀ compounds are discussed. The compounds were identified by ¹H and ¹⁹B NMR, IR, mass spectrometry, and elemental analysis. / Master of Science