Thesis (Ph. D.)--University of Wisconsin, 1966. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin, 1967. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 167-185).

Thesis (Ph. D.)--University of Chicago. / From American chemical journal, v. 38, p. 561-594. Also available on the Internet.

An effective method for the stabilization of otherwise unstable thiones is their complexation to M(CO)5 (M= Cr, Mo, W). This complexation led to a very stable material of composition C22H14CrFeO5S, whose crystals are triclinic, space group PI (No. 2) with a=9.058(7), b=10.040(7), c=12.568(8) Å, α=113.70(5), β=93.42(6), γ=95.25(6)° and Z=2. The structure was refined from diffractometer data to an R value of 0.0049. The structure was found to be that of pentacarbonyl(thiobenzoylferrocene-S) chromium, in which the Cr(CO)5 fragment is bonded to the sulphur atom of the thioacyl ferrocene. The photodegradation product was found to have a composition of C17H14FeO, crystals were monoclinic, space group P21 (No. 14) with a=6.09(6), b=15.145(7), c=14.263(4)Å, β=105.91(1)° and Z=4. The structure was refined to an R value of 0.059, and was found to be benzoylferrocene. 1,1'-Dibenzoylferrocene reacts with tetraphosphorus decasulphide to yield, in addition to the expected 1,1'-bis(thiobenzoyl)ferrocene, a minor, yellow by-product of composition C24H18FeS3, whose crystals are monoclinic, space group P21/n with a=11.769(3), b=11.750(4), c=14.835(2) Å, β=98.63(1)°, and Z=4: the structure was found to be that of 1,4-diphenyl-1,4-epithio-2,3-dithia[4](1,1')-ferrocenophane in which the two rings of the ferrocene nucleus are spanned by a 1,2,4-trithiolane ring. Whereas the reaction of ferrocene with a stoichiometric quantity of Me3CCOCl/AICI3 provides the monoacylated product in 87% yield, the use of excess of the acylation reagent leads to simultaneous acylation and alkylation, two products of which have been isolated and characterised by 1H and 13C NMR, spectroscopy as 1,1/3-tri-t- butyl-3'-(2,2-dimethylpropionyl) ferrocene, [C5H3(CMe3)2] Fe [C5H3(CMe3)COCMe3)] and 1,1'-di-t-butyl-3,3'-bis(2,2-dimethylpropiony)ferrocene, [C5H3(CMe3)(COCMe3)]2Fe . Flash Vacuum Pyrolysis of a number of ferrocenes have been carried out and the mono and diacyl ferrocenes were found to display a high degree of thermal stability, most of these being recovered in almost quantitative yields at furnace temperatures up to 700 °C. Ferrocenecarboxaldoxime acetate was found to yield cyanoferrocene and acetic acid in a clean reaction in which the cyanoferrocene was uncontaminated with the acetic acid. Crystals of the low melting form of ferrocenecarboxaldoxime, (C5H5)Fe(C5H4CH = NOH) are monoclinic, space-group C2/c with a= 26.512(6), b = 12.798 (4), c = 12.855 (2)Å, β = 114.37 (1)°, and Z = 16. The structure was refined from diffractometer data to an R value of 0.054. There are two molecular sites in the asymmetric unit, and both sites contain a disordered mixture of E and Z geometrical isomers. There are no close contacts between the iron atom and the hydroxyl group of the oxime substituent, but rather there is extensive intermolecular hydrogen bonding.

A six-step synthesis of salbutamol from methyl salicylate with an overall yield of 17% has been completed, although the yield was not optimised. In the process, Zn(BH4)2 was found to selectively reduce a ketone carbonyl group in the presence of an ester unit. In contrast, borane was found to reduce both the ketone and ester carbonyl groups. Reduction of phenacyl bromide with borane in the presence of chiral catalysts based on (R)-alaninol and (R,S)-ephidrine resulted a measure of enantioselectivity in the product. However, the configuration of the alcohol obtained in the case of (R)-alaninol was contrary to expectations based both on experimental trends observed elsewhere as well as our own theoretical predictions. The asymmetric reduction of methyl 5-bromoacetyl-2-benzyloxybenzoate was accomplished with both borane and Zn(BH4)2 in the presence of a range of chiral catalysts. Optically active products were obtained in all cases, although the optical rotations were significantly smaller in the case of Zn(BH4)2. Unfortunately, we were not successful in determining the enantiomeric excesses of these reactions. The use of a NMR lanthanide shift reagent resulted in a complex spectrum that was impossible to interpret unambiguously. This presumably arises from the presence of several Lewis base sites in the product at which complexation with the shift reagent can take place. It was also not possible to determine the optical rotation of salbutamol itself owing to the relatively small amount of material obtained. A conformational analysis of salbutamol, where NMR data was correlated with molecular modelling results, was successfully carried out and revealed a strong preference for that conformer family characterised by O–C–C–N and Ar–C–C–N torsion angles of ca. 60º and 180º, respectively. Interestingly, these conformers are found to be stabilised by OH…N rather than NH…O hydrogen bonding. This study has also confirmed the effectiveness of the MMFF94 force field for conformational analysis studies in compounds of this kind. Lastly, a relatively simple method for modelling the BH3/oxazaborolidine reduction of ketones at the PM3 semiempirical MO level of approximation was devised. This approach has provided insights into the mechanism of the reaction and has furthermore enabled us to predict the enantioselectivities likely to result from various catalysts and ketones. In comparing our theoretical and experimental findings, an anomalous result was observed in the case of (R)-alaninol; this will have to be investigated further, particularly at the experimental level. However, we believe that our approach provides a sound basis for aiding the design and screening of new, potentially better catalysts.

The crystal structure of diferrocenyl ketone has been analyzed using Fe(Kα) X-radiation. The molecule is symmetrical about a 2-fold axis passing through the carbonyl bond. Coordinates of the iron atom were determined from two Patterson-Harker sections and coordinates of the remaining atoms were derived from subsequent three dimensional Fourier summations. Structure refinement was carried out using (block-diagonal) least squares with allowances for anisotropic temperature vibration. The R value derived from the final coordinates is 0.09. The cyclopentadienyl rings not bonded to the keto group are vibrating more than those which are; when this is taken into account the iron atom lies midway between the cyclopentadienyl rings which are planar and 3.30 Å apart. The carbon bond lengths in these rings are all the same length (1.45 Å) and the conformation of one ring with respect to the other is almost eclipsed. The intermolecular contacts are all of normal length. The molecular dimensions of anti-8-tricyclo [3,2,1,0²˒⁴] octyl p-bromobenzenesulphonate and anti-7-norborneny1 p-bromo-benzoate have been measured to assist in the interpretation of the solvolytic reactivity in norbornane derivatives. Data were collected (Cu(Kα) radiation) by counter methods in both cases; the structures were determined using the heavy atom-Patterson method and refinements were carried out using differential syntheses and (block-diagonal) least squares. The discrepancy factors derived from the final coordinates are 0.09 and 0.18 respectively. The norbornane and norbornene skeletons have symmetry m and the bond lengths are normal. The bond angles at the methylene bridge are 97° and 96° respectively, the other angles are all less than the tetrahedral angle. The angles between the planes formed by different parts of the skeleton are identical in both cases. Bond lengths and angles in the remainders of both molecules are of normal dimensions. The configuration of the cyclopropyl methylene group in anti-8- tricycle [3,2,1,0²˒⁴] octyl p-bromobenzenesulphonate is exo to the norbornane skeleton. The results indicate that there is insufficient variation in the methylene bridge bond angles to account for the difference in solvolytic reactivity. The crystal and molecular structure of ochotensine methiodide has been investigated in order to determine the chemical structure of the molecule. The data were recorded photographically using Cu(Kα) radiation and a Weissenberg equi-inclination camera; estimation of the intensities was carried out by visual methods and interfilm scales were derived from corresponding symmetry related structure amplitudes. 845 independent reflections were measured in this way. The position of the iodine atom was determined from a three dimensional Patterson function and the positions of the remaining atoms from three subsequent three-dimensional Fourier maps. Refinement of the temperature and atomic parameters was carried out by (block diagonal) least squares; the final R value was 0.11. The analysis has shown that the structure of ochotensine is similar to that postulated for ochotensimine and the position of the phenolic group on ring A has been determined. A difference synthesis was carried out to verify the positions of the atoms. The bond lengths and angles are normal but several short intermolecular contacts were observed. The planes of the two benzene rings are inclined at an angle of 94°. / Science, Faculty of / Chemistry, Department of / Graduate

The effect of exercise on the total ketone body (acetoacetate + D-3-hydroxybutyrate) concentrations in the blood was studied to find out whether the susceptibility of non-athletes, compared with athletes, to develop post-exercise ketosis is the result of the former's increased reliance on glycolysis during exercise. In the first experiments, use was made of the diving reflex to induce peripheral vasoconstriction during exercise in both physically trained and untrained subjects. It was hoped that under these circumstances athletes and non-athletes would utilize similar amounts of muscle glycogen during exercise, and therefore develop similar degrees of ketosis after exercise, if the glycogen content of the muscles was in fact the factor which determined post-exercise ketosis. Ten non-athletic subjects, six long-distance runners, and three competitive swimmers were therefore studied before, and for 9½ hours after swimming in the early morning. The last meal was eaten during the evening before the swim. On the first test day the subjects swam underwater for as far as they could go three times in succession. A week later the same distance was swum on the surface without breath-holding. There was no increase in the post-exercise blood ketone body concentrations in any of the subjects after either form of the exercise, compared with control day values (when the subjects fasted, but did not swim at 07h30). Similar results were obtained when healthy young medical students (aged 18 - 23 years; trained and untrained) performed maximal exercise for 15 minutes, or moderate exercise for up to 90 minutes, on a bicycle ergometer. When six older subjects (aged 30 - 51 years) exercised at 75 W for 90 minutes, three of them developed ketonaemia, which reached its maximum intensity about three hours after exercise. The exercising heart rates of these older subjects were similar to those of the younger non-athletic subjects who had performed the same exercise, but had not developed post-exercise ketosis., An extra 60 - 90 g sucrose in the diet of the subject who had developed the most marked post-exercise ketonaemia, abolished the response, whereas carbohydrate restriction intensified it. A protein-fat diet caused two well trained marathon runners to develop the highest post-exercise blood ketone body levels yet recorded (3,88 mmoles/l). Free fatty acid, glucose, growth hormone and insulin concentrations in the serum followed patterns different from the ketone body levels during, and for 7 ½ hours after exercise, but were also affected more by diet than by training. Post-exercise ketosis, previously ascribed to a lack of athletic training, could equally well be ascribed to the lower carbohydrate intake of sedentary subjects compared with athletes: the two marathon runners were estimated to eat about twice as much carbohydrate in their regular diet than the sedentary subject who had developed post-exercise ketonaemia without carbohydrate restriction. The final experiments were designed to find out whether post-exercise ketosis was the result of the low levels of glycogen in the body, or of the gluconeogenesis which occurs after exercise to replenish the carbohydrate stores. Twenty-four highly trained athletes were therefore studied after prolonged exercise following a protein-fat diet to induce post-exercise ketosis. Six of them were then given 100 g alanine to take by mouth, six ingested 100 g glucose, six ingested 100 g starch, and the remaining six acted as controls. It was found that both alanine and glucose ingestion reduced the blood ketone body concentration from about 2 mmoles/l to less than 0,4 mmoles/l in 3 hours. Starch had a minimal effect on the blood ketone body levels during the 5-hour observation period. Alanine and glucose exerted their antiketogenic effects in the context of widely different serum insulin, glucagon and growth hormone concentrations. Similar results were obtained in starvational ketosis, and even in normoketonaemic subjects. The results indicate that ketogenesis is not the result of gluconeogenesis, nor of a low insulin/glucagon (+ growth hormone) ratio in the blood. It is concluded that low levels of glycogen, or of a metabolic intermediary of glycogen metabolism (such as glucose-1-phosphate, or glucose-6-phosphate) in the liver is probably the single most important stimulus for ketogenesis after exercise and starvation.

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