Some new reactions in organic synthesis

Doctoral thesis English OPEN
Hall, David R.
  • Subject: QD

The first part of this thesis is concerned with work towards the total synthesis of ß-lactam antibiotics, and a second part deals with two topics arising from the author's contribution to research on cobaloximes being conducted in these laboratories.\ud \ud The introduction to ß-lactam antibiotics describes characteristics related to their biological action and synthesis. Published synthetic methods are discussed as routes to analogues of penicillins and cephalosporins, particularly those in which sulphur is replaced by oxygen. Synthesis of such an oxa-penam by photocyclisation of an a-diazoamide is described in chapter 2. \ud \ud Attempts to synthesise more stable oxa-penams are the subjects of chapters 3 and 4. Formation of the C5-C6 bond of an oxapenam by radical-induced cyclisation of N-acyloxazolidines was not achieved photochemically, or chemically with azo-bis-isobutyronitrile or nickel peroxide. The former two sets of conditions initiated oxidation of the oxazolidine ring, and azo-bis- sobutyronitrile also effected a characteristic cleavage of peptide derivatives. Nickel peroxide caused trimerisation of some amides and an ester of cyanoacetic acid to derivatives of 1,2,3-tricyanocyclopropane. \ud \ud Reaction of acyl chlorides and triethylamine with 2-oxazolines did not give ß-lactams. 1:1 Adducts of acyl chlorides and oxazolines were identified as reaction intermediates, and the products analysed in the particular case of phthalimidoacetyl chloride.\ud \ud Chapter 5 describes the reactions of vicinal diols with hydrogen bromide in acetic acid. Certain such diols are converted rapidly and stereospecifically to vicinal acetoxybromides via an intermediate 2-methyl-l,3-dioxolan-2-ylium ion formed by 'frontside' participation. Applicability and limitations of this reaction as applied to a range of acyclic and cyclic diols is discussed.\ud \ud In the final chapter, the product of a degradation of alkylcobaloximes by acetic anhydride in pyridine is proved to be a derivative of imidazo[1,2-a]pyridine by chemical methods and single crystal X-ray analysis. Limited studies on the reaction mechanism and its relation to coenzyme B12 action are discussed.\ud
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    24 references, page 1 of 3

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