M.S.

1. The chemical properties of 3-methyl-2, 5-dihydrothiophene 1, 1-dioxide have been studied including ionic additions, radical initiated reactions, Diels-Alder reactions, ietalation, condensation, and oxidation and reduction reactions. 2. For the first time the introduction of one halogen atom into the unsaturated five-membered cyclic sulfone without the isomerization of the double bond was accomplished. 3. The properties of 3-bromomethyl-2, 5-dihydrothiophene 1, 1-dioxide have been investigated including displacement reactions, allylic rearrangement, Diels- Alder reaction, pyrolysis and salt formation. 4. A synthesis of conjugated, substituted dienes was illustrated by the synthesis of 2-bromomethyl- 1,3-butadiene. 5. A novel Diels-Alder reaction between 3-bromomethyl and 2,5-dihydrothiophene 1, 1-dioxide has been described. 6. The structure of 3-bromomethyl-2, 5-dihydrothiophene 1, 1-dioxide was supported both by pyrolysis studies and by the above mentioned Diels-Alder reaction. The structure of the pyrolysate, 2-bromomethyl- 1,3-butadiene, was substantiated by both infrared and ultraviolet evidence. 7. Isomeric monobromo dihydrothiophene 1, 1-dioxides have been prepared via elimination reactions of the isomeric dibromo tetrahydrothiophene 1, 1-dioxides. Their structures have been supported by ultraviolet absorption studies. 8. Evidence for the allylic rearrangement of 3-bromomethyl-2, 5-dihydrothiophene 1, 1-dioxide was achieved through ultraviolet absorption studies. 9. A simple method for the identification of alkyldinydrothiophene 1, 1-dioxides was demonstrated. 10. The modified Prilezhaev oxidation has been applied to 3-methyl-2,5-dihydrothiophene 1, 1-dioxide. 11. The addition of chlorine and of hydrogen iodide to 3-methyl-2,5-dihydrothiophene 1, 1-dioxide was accomplished. 12. The formation of the quaternary salts from 3-bromnomethyl-2, 5-dihydrothiophene 1, 1-dioxide and nitrogenous bases was found to be of general application. The use of certain salts as synthetic intermediates was attempted. / Ph. D.

Heterocyclic compounds are prevalent in all biological systems and are essential to the maintenance of life. The synthesis of natural products is continuously pursued to make available large enough quantities to be used in medicinal research. The functionalization of available starting materials provides an approach to a synthetic plan in which methylheteroaromatics offer a simple keystone. At present the use of sodium hydride for the introduction of appropriate building blocks onto a side-chain in heteroaromatics does not appear to have been studied. In this connection the acylation of a series of methylheteroaromatics was studied using sodium hydride in dimethoxyethane (DME). The use of multiple anions of methylheteroaromatics was also investigated in several model systems. These methods offer a convenient means of drug design in a variety of different heterocycles of medicinal importance. / Ph. D.

The positive and negative ion mess spectra and appearance potentials were determined for the following compounds: benzil, 4-methylbenzil, 4- methoxybenzil, 4-methylmercaptobenzil, 4-dimethylaminobenzil, 4-chlorobenzil, 4—nitrobenzil, 4,4'-dimethylbenzil, 4,4'-dimethoxybenzil, 4,4'- bis(methylmercapto) benzil, 4,4'-bis(dimethylamino)benzil, 4,4'-dichlorobenzil, and 4,4‘-dinitrobenzil. Metastable data were used to establish that the fragmentation mechanism for positive ions involves cleavage between the carbonyls followed by loss of CQ. Calculated appearance potentials are compared wilh those generated experimentally. The appearance potentials of the substituted benzoyl ions exhibit substituent effects correlatable with the Hammett σ, but no substituent effect is demonstrated for the unsubstituted benzoyl. Loss of CO by the benzoyl ion does not appear to involve substituent effects but required 2.5-4.0 eV excess energy above that required to form the precursor. The nitro-substituted benzils fragment by two competing mechanisms, that described supra and the loss of NO⋅ following rearrangement of the substituent. The base peak in all negative ion spectra at 50 eV was the parent-molecule jon. Benzil, the methyl-substituted benzils, and the dimethyl-amino- substituted benzils form no daughter ions. The methoxy-substituted benzils and the nethyimercapto-substituted benzils formed a daughter jon by loss of CH₃⋅ from the parent, The echloro-substituted benzils fragment to produce Cl⁻. The nitro-substituted benzils lose NO⋅, apparently following a rearrangement Similar to that observed for positive ions, and also fragment to lose NO⁻ in low abundance. Appearance potential data indicate that all parent-molecule ions are formed by electron capture, and all fragments by dissociative-attachment. The electron-withdrawing substituents cause a broadening of the ionization efficiency curve for the parent-molecule ion; all other substituents have no effect on the curves' shape. Daughter ion ionization efficiency curves are broader than the parent-molecule i.e. curves, and the i.e. curves for the daughter ions from the methoxy-substituted benzils appear to be conmposits of at least two curves. NO⁻ and Cl⁻ are of low abundance, with onset at 2.2 eV and 5.5 eV respectively above SF¯₆. The most abundant negative daughter ions are resonance stabilized; Cl⁻ and NO⁻ are formed by electron pairing at an electronegative site. Negative ions are not formed with sufficient excess energy to fragment by the same mechanism as positive ions, with the exception of the anomalous nitro-substituted mechanism. Polarographic half-wave potentials were compared to negative ion mass spectrometric data. Benzils with electron-donating substituents fit a plot of E_1/2 vs.o. Substituent effects for these benzils are additive, as indicated by comparison of Ag for one and two substituents to that for benzil. Chloro-substituted and nitro-substituted benziils have second waves at only 0.3 to 0.4 v more negative than the first wave, in contrast to 0.6 to 0.8 v differences for the other benzils. Loss of a substituent, as observed in the negative ion mass spectra, is suggested as an explanation E_3/4 - E_1/4 values were calculated and indicate that waves in the region 1.0 to 1.4 v are probably reversible. / Ph. D.

Carbonyl fluoride will add to alkyl and perfluoroalkyl nitriles and alkane dinitriles in anhydrous acids to form the corresponding α,α-difluoroalkyl isocyanate, perfluoroalkyl isocyanate, or α,α,ω,ω-tetrafluoro- α,ω-diisocyanatoalkane. With acetonitrile the reaction proceeded slowly in anhydrous hydrogen fluoride or hydrogen chloride to yield a clear colorless liquid which was identified by infrared, mass, proton NMR, and fluorine-19 NMR spectroscopies to be a,a-difluoroethyl isocyanate. Increasing yields based on the lesser reactant were achieved by making the ratio of acetonitrile to carbonyl fluoride greater or less than one, having the optimum amount of anhydrous acid, the presence of an alkali metal fluoride and/or an increase in reaction time. The a,a-difluoroethyl isocyanate reacted with anhydrous ethyl alcohol to form the carbamate which slowly decomposed by splitting out hydrogen fluoride. The addition reaction proceeded more rapidly, in comparison to acetonitrile, with propionitrile and less rapidly with trifluoroacetonitrile. Cyanamide yielded trifluoromethyl isocyanate and cyanuric acid. Adiponitrile produced 1,6-diisocyanato-1,1,6,6- tetrafluorohexane and 1-isocyanato-5-cyano-1,1-difluoropentane. Carbonyl fluoride will add to arylformonitriles in the presence of anhydrous hydrogen fluoride and alkali metal fluorides to produce the corresponding aryl-α,α-difluoromethyl isocyanate. The reaction proceeded more rapidly in the presence of alkali metal fluoride and at elevated temperatures. Increasing yields were achieved by having carbonyl fluoride in excess of the nitrile and the optimum amount of anhydrous hydrogen fluoride. The aryl-α,α-difluoromethyl isocyanates reacted with two additional moles of aryl formonitrile to yield aryltrifluoromethanes and 2-hydroxy-4,6-diaryl-s-triazines. Alkali metal fluorides also enhanced this reaction and suppressed the formation of 2,4,6-triaryl-s-triazine. Hith an electron withdrawing substituent on the aromatic ring, the reactions did not yield any significant quantity of the aryltrifluoromethanes but stopped at the aryl-α,α-difluoromethyl isocyanate stage. In the case of o-tolunitrile, steric hindrance prevented the formation of the isocyanate as well as of the trimer. Pentafluorosulfanyl isocyanate was prepared by the addition of carbonyl fluoride to thiazyl trifluoride in the presence of anhydrous acids. Increasing the concentration of anhydrous hydrogen fluoride resulted in decreasing yield of the isocyanate while without an acid no isocyanate was formed. Pentafluorosulfanyl isocyanate in an excess of anhydrous hydrogen fluoride yielded the starting products. Isolated from anhydrous hydrogen chloride-catalyzed reaction was pentafluorosulfanyl carbamoyl chloride. N,N'-bis(pentafluorosulfanyl)urea was synthesized from pentafluorosulfanyl isocyanate and pentafluorosulfanyl amine or from thiazyl trifluoride, anhydrous hydrogen fluoride, and carbonyl fluoride. The reaction was reversible in excess anhydrous hydrogen fluoride or when heated under vacuum to over 90° C. With triethylamine the urea decomposed. Mercuric isocyanate does not produce mercuric imino sulfur difluoride by reaction with sulfur tetrafluoride. Thiazyl trifluoride and ammonia react at low temperature to produce a white unidentified compound, possibly NS(NH₂)₃. Thiazyl trifluoride and diacetamide react in triethylamine to produce a compound which apparently decomposes immediately to give unidentified products. The decomposition proceeds even at ice water temperatures. / Ph. D.

A kinetic study of the suprafacial [1,5]-sigmatropic phenyl rearrangements of 3,4-bis- (para-substituted)-1,2,5-triphenyl-2,4- cyclopentadien-1-ols to 3,4-bis-(para-substituted)-2, 2,5-triphenyl-3-cyclopenten-1-ones, where the substituent were, t-butyl, methyl, hydrogen, chloro and bromo, has been performed at 180, 190, 200 and 210 ± 0.2° in tetraethylene glycol. The rearrangement was observed to be first order throughout the temperature range investigated, and the rate constants (k) at the temperatures used were found to be 8.057, 2.143, 2.930 and 6.456 x 10⁻⁴ sec⁻¹ for the t-butyl substituent; 4 7.700, 2.110, 3.434, and 6.581 x 10⁻⁴ sec⁻¹ for the methyl substituent; 0.909, 2.166, 3.678 and 6.448 x 10⁻⁴ sec⁻¹ for the unsubstituted alcohol; 1.469, 2.992, 5.989 and 11.12 x 10⁻⁴ sec⁻¹ for the chloro substituent; and 1.955, 3.215, 6.215 and 13.01 x 10⁻⁴ sec⁻¹ for the bromo substituent, respectively. . Calculations of the activation energy of this phenyl [1,5]-sigmatropic shift from the Arrhenius equation give values of 28.71, 30.31, 28.01, 29.38 and 27.49 kcal·mol⁻¹ for the above substituents respectively, while ΔH^‡ these phenyl migrations were 27.78, 29.39, 27.93, 28.45 and 26.56 kcal·mol⁻¹ respectively. ΔS^‡ values were also calculated to be -16.6, -13.1, -16.1, -14.0 and -17.8 eu, respectively for a mean temperature range of 453-483 ± 0.2°K. The isokinetic temperature was calculated to be 320°. Calculated rho (ρ) values for the sigmatropic migrations were -0.813, -0.400, -0.690 and -0.658 at 180, 190, 200 and 210 ± 0.2°C. These results are used to discuss both the mechanism of this rearrangement and the transition state for rearrangements in the pentaphenylcyclopentadienol system. Ina much broader sense these results and the results of previously documented sigmatropic rearrangements exhibiting electronic influences were used to formulate a general scheme to predict the outcome of those sigmatropic rearrangements that entail an electronic effect as seen in the rates of the above reactions. This scheme used as its basis the transition state approach invoking inductive and mesomeric arguments to rationalize the observed rates of the sigmatropic rearrangements of this dissertation, those of previously documented sigmatropic rearrangements and finally to predict a relative rate of rearrangements in general. Finally a mass spectral investigation of the fragmentation patterns of 1-para-phenylsubstituted 2,3,4,5-tetraphenyl-2,4-cyclopentadien-l-ols and 3,4-bis(para-substituted phenyl)-1,2,5-triphenyl-2,4- cyclopentadien-1-ols was undertaken. A continuum of two super imposable pathways with the choice of the major decomposition mode being determined by the electron donating or withdrawing ability of the substit- vent was established. Linear free energy relationships for mass spectral decomposition were presented as well as a justification for this behavior. / Ph. D.

The direct decay induced ⁸²Br (or ⁸⁰Br) labelling by exposing the solid substrate molecules, such as deoxyuridine, L-tyrosine, guanosine, deoxycytodine, phenylalanine and acetic acid, to gaseous CF₃^82mBr (or CF₃^80mBr) was studied. The radiochemical yields of the brominated products are relatively small and range from 1% in the case of bromo-deoxyuridine to 11% for bromoacetic acid. The modification of this technique by adding Cl₂ gas to the reaction mixture improves the yields in several cases drastically (up to 80% for bromo-guanosine and bromo-L-tyrosine). Similar improvement can be achieved by exposing crystalline KBrO₃ for some time to CF₃^82mBr (or CF₃^80mBr) and dissolving subsequently the KBrO₃ in an acidic solution of the substrate. The radiochemical yields of ⁸⁰Br-5-bromodeoxyuridine and ⁸⁰Br-bromoacetic acid obtained by employing various modifications of the direct decay induced ⁸⁰Br labelling method which exposes substrate molecules to gaseous CF₃^80mBr are reported. The results indicate a drastic improvement of the amount of Br incorporated into these products if the labelling is accomplished by applying the “CF₃^80mBr-KBrO₃” gas exposure technique to induce a ⁸⁰Br for I exchange in the corresponding (inactive) iodo derivatives. The effect of several experimental conditions, such as the labelling time, the pH of the labelling medium, and the concentration of the substrate solutions, on the efficiency of the ⁸⁰Br incorporation via the “CF₃^80mBr-KBrO₃” gas exposure method resulting in carrier free radiobrominated compounds was investigated by using two model compounds, L-tyrosine and guanosine. The ⁸⁰Br labelling proceeds very rapidly in the case of the L-tyrosine and is fairly independent of “labelling time" and substrate concentration as long as a certain minimum amount of L-tyrosine is used. This is in contrast to the guanosine system where rapid secondary reactions reduce the initially high yields of ⁸⁰Br-guanosine at extended "labelling times” and where larger amounts of substrate are needed to produce optium yields. The chemical stability of ⁸⁰Br-guanosine and ⁸⁰Br-tyrosine was established by studying the dependence of the radiochemical yield on “labelling time” ( CF₃^80mBr-KBrO₃ gas exposure method ) and “post-labelling time” ( CF₃^80mBr-Cl₂ gas exposure method ). A radiochemical yield-time index is proposed to summarize the radiochemical yield dependence on “labelling” and “post-labelling” times in these two modified gas exposure labellings. It is hoped that this index will be helpful in making a priori judgements on the applicability of these labelled biomolecules for nuclear medical studies. Some preliminary mechanistic studies were carried out by using different reactants and model compound aniline. The proposed mechanism for both the direct excitation labelling and the CF₃^80mBr-KBrO₃ gas exposure method is electrophilic. / Ph. D.

A brief investigation was made of various enzymes such as urease in conjunction with a wetting agent, ficin, steapsin, and hyaluronidase as aides in the :in vitro" dissolution of calculi in "G"⁷ solution. This investigation indicated that a more effective solvent was needed. / Master of Science

Size Exclusion Chromatography (SEC) is a liquid chromarographic technique used for the characterization of polymers and polymer related materials and also for the separation of small molecules. The major drawback of SEC is the lack of availability of a universal and true mass detector for providing a homogeneous response for all samples. Indirect detection methods have demonstrated to supply an alternative way to obtain a universal, sensitive and mass response in liquid chromatography. This research evaluated the indirect conductivity detection method for the size exclusion chromatographic separation of small molecules. Several studies were developed in order to understand the performance of this novel indirect detection mode. The evaluation of the initial experimental conditions snowed a dependence on the response, efficiency and elution time with the concentration of the conductivity probe added to the mobile phase. The SEC calibration curves developed for a series of standards indicated that selected conditions do not affect the separation by size. Response factors revealed a slight increase with molecular weight when they are expressed in volume or mass. Limits of detection were in the order of 20 nanoliters for small molecules. The effect of different conductivity probes on the separation and response was also studied. A modification of the original detector cell design resulted in improvement in the signal to noise ratio. / Master of Science

Aqueous dispersion pre-pregging is under investigation within our laboratories for processing fiber reinforced, polymer matrix composites with environmental concern by using water instead of toxic organic solvents. This method requires that the polymers be in the form of a stable aqueous colloidal dispersion. This thesis describes the preparation of submicron diameter poly(arylene ether ether ketone) suspensions in water, and analysis of suspension stability as a function of the suspension variables. This thesis focuses on developing the procedures, and defining the parameters, for preparing stable aqueous suspensions of PEEK particles using new pyridine containing electrostatic stabilizers. Preparation of aqueous PEEK suspensions involves first adsorbing a soluble stabilizer precursor, poly(pyridine ether-co-ether ether ketimine), onto PEEK particles from a organic solvent, followed by hydrolysis of the ketimine moiety on this particle coating in conjunction with protonation of the pyridine units, forming a protonated form of poly(pyridine ether-co-ether ether ketone), which acts as an electrostatic aqueous stabilizer. Ultraviolet spectroscopy was employed to measure and compare adsorption isotherms in both THF and toluene. This high performance electrostatic stabilizer has been used successfully to stabilize aqueous suspensions of both larger particles (~ 12 micron diameter PEEK particles), as well as submicron particles. Stabilities of the suspensions were analyzed using sedimentation experiments for the larger particle size range, and using light scattering (turbidity) for the submicron sizes. The research accomplished in this thesis is currently being used to investigate the use of these dispersions for pre-pregging both continuous carbon fiber tow and pre-woven graphite fabric. / Master of Science