Part I, The Hofmann Rearrangement. First-order rate constants and activation parameters were determined for the rearrangement of eleven N-halogenoamides. The structures of the N-halogenoamides (RCO.NHX) differed in the leaving group (X = chlorine or bromine) and the migrating group (R=ethyl, isopropyl, t-butyl, diphenylmethyl, benzyl, phenyl or p-tolyl). N-Bromoamides and the corresponding N-chloroamides rearranged at similar rates. When the leaving group was changed from bromide to chloride the activation energy was reduced by about one kcal. mole-1 and the activation entropy was reduced by about three cal. deg.-1 mole-1. Differences in the reactivity of halides as leaving groups from carbon and nitrogen are discussed. Changes in the structure of alkyl migrating groups resulted in small irregular changes in the activation parameters. The kinetic data were consistent with a stepwise rearrangement mechanism in which halide departed from nitrogen in the rate-determining step to give a short-lived nitrene intermediate which subsequently rearranged to an isocyanate. Other aspects of the Hofmann rearrangement were investigated. In the Hofmann reaction of amides and hypobromite, N-bromination of the amide was found to be much faster than the rearrangement of the intermediate N-bromoamide conjugate base. In contrast, when amides and hypochlorite reacted in alkaline solution N-chlorination was not fast by comparison with the rearrangement of the intermediate N-chloroamide conjugate base. Oxygen, iodide, and hypobromite did not inhibit the Hofmann rearrangement. Rearrangement of N-brmoacetamide N-bromopropionamide, N-bromoisobutyramide and N-bromopivalamide in the presence of oxygen gave traces of nitrite as a by-product. Nitrite may result from the capture of an intermediate nitrene by oxygen. Ionisation constants of six N-bromoamides and one N-chloroamide were measured. Of the N-halogenoemides which were investigated, the most acidic was N-chloroperfluorobutyramide (pK 2.45) and the least acidic was N-bromopropionamide (pK 7.95). There are no ionisation constants of N-halogenomides recorded in the chemical literature. Part II, The Rearrangement of N-Bromo-α-halogenamides and N-Bromoperhalogenoamides. Previous investigators of the rearrangement concluded that the conjugate base of the N-halogenoamide rearranged intramolecularly via a cyclic four-membered transition state to give an alkyl halide and cyanate ion. This mechanism is incompatible with evidence presented in this thesis. The arrangements of N-bromoperfluorobutyramide and N-bromo-α-chloroisobutyramide in alkaline solution were not first-order reactions. In neutral aqueous solution, the N-halogenoamide conjugate bases did not rearrange. However, in the presence of an excess of hydroxide ion, the N-halogenoamide rearranged readily. The rearrangement was catalysed by hydroxide ion and ammonia and inhibited by many reagents including oxygen, hypobromite, iodide, cupric hydroxide, silver oxide, and amides of carboxylic and sulphonic acids. Possible rearrangement mechanisms are discussed. The effects of small proportions of the inhibitors showed that the rearrangement was a chain reaction. Two probable steps in the chain reaction are the addition of hydroxide ion to the N-halogenoamide conjugate base to give a dianionic intermediate and heterolysis of the nitrogen-bromine bond in this intermediate to give a nitrene. Part III, The Reaction of Mandelamide and Hypohalite. In alkaline solution, mandelamide and hypohalite yield benzaldehyde, cyanate and halide. Several mechanisms which were postulated by previous investigators are excluded by evidence presented in this thesis. Evidence for an N-chloromandelamide intermediate in the reaction of mandelamide and hypochlorite was obtained. Chlorination of mandelamide in neutral or acidic solution gave N-chloromandelamide and N,N-dichloromandelmide. In alkaline solution, the N-chloromandelamides decomposed to give benzaldehyde and cyanate. This reaction was much faster than the reaction of mandelamide and hypochlorite to give the same products. The reactions of hypobromite and hypoiodite with mandelamide were also investigated. Neither oxygen nor an excess of hypobromite inhibited the reaction of mandelamide and hypobromite to give benzaldehyde and cyanate. Hypoiodite (prepared from the reaction of hypochlorite and iodide) and mandelamide also gave benzaldehyde and cyanate in high yield. The mechanism most consistent with the evidence involves the rearrangement of an intermediate N-halogeno-α-hydroxyamide conjugate base to an α-hydroxyalkyl isocyanate which subsequently decomposes to benzaldehyde and cyanate. Mechanisms involving dianionic intermediates were disproved. Stoichiometric similarities in the rearrangements of N-bromo-α-halogenoamides and N-halogeno-α-hydroxyamides were shown to be fortuitous and not the result of similarities in the rearrangement mechanisms. Part IV, Preparation of Amides, N-Bromoamides, and N-Chloroamides. Preparations of amides and N-halogenoamides used in this thesis are described. Some of the N-halogenoamides have not been reported previously. Methods for preparing N-bromo-perhalogenoamides which are described in the chemical literature involve the bromination of the silver salt of the perhalogenoamides in trifluoroacetic acid solution. A much simpler method for preparing N-halogenoperhalogenoamides is described in this thesis.
| Identifer | oai:union.ndltd.org:ADTP/276071 |
| Date | January 1967 |
| Creators | Judd, William Paul |
| Publisher | ResearchSpace@Auckland |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated., http://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm, Copyright: The author |
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