In this course of their work J. Risi and A. Labrie (1) found that guaiacol and vanillin were among the products derived from the sap of the sugar maple. By using a five percent sucrose solution and equal quantities of vanillin and guaiacol, a little calcium malate and manganese acetate, they obtained an amorphous powder possessing no odor of vanillin or guaiacol but having an odor greatly resembling the odor of the extracts of the sugar maple. This work is an investigation of the actual products of the reactions involved and the mechanism pertaining thereto. It is proposed to study this problem by carrying out the experiment of Risi and Labrie except that the constituents guaiacol, vanillin and sucrose will be used first one at a time, then two at a time and finally all together in an effort to determine the reaction and its mechanism. The following conclusions have been drawn from the work done: 1. The author has been unable to duplicate the work of Risi and Labrie by following their brief directions. 2. Several modifications of their procedure failed to produce the product described. 3. No change was found when each component was used alone in any of the modifications. 4. No change was found when the components were used two at a time in any of the modifications used. 5. No change was found using all three components in any of the modifications used. / M.S.

M.S.

Ferrous sulfate, commercially known as copperas, is a by-product of many industries such as the steel industry where steel is “pickled” in sulfuric acid previous to galvanizing, and in ore refining where sulfuric acid is used to remove undesirable impurities consisting chiefly of iron materials. One of the chief uses of copperas is as a coagulant in water treatment. Crude copperas, as produced, does not meet these specifications and must be refined and reworked before it is suitable for use. Consequently, in many instances no attempt is made to make further use of the copperas and it is dumped aside as refuse. It is the purpose of this investigation to use this crude copperas to produce an iron salt suitable for use as a coagulant. Crude copperas can be used to make a solution of ferric chloride by reacting it with calcium chloride, filtering off the precipitate of calcium sulfate, and oxidizing the ferrous iron to ferric iron with chlorine gas. The calcium content of the ferric chloride solution is low enough so that the hardness of water treated with i it will not be appreciably increased. / M.S.

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.