Studies in the pyrazolidine and metal chelate fields

Murdoch, Henry D (1961) Studies in the pyrazolidine and metal chelate fields. PhD thesis, University of Glasgow.

Abstract

PART I The discovery of 4-n-butyl-3,5-dioxo-1,2-diphenyl-pyrazolidine (Phenylbutazone), and its therapeutic value in the treatment of rheumatoid arthritis, has instigated an extensive study of pyrazolidine derivatives in an attempt to obtain a drug with the physiological activity of phenylbutazone, but without its attendant toxicity. Synthesis of 3-imino-5-oxo-1,2-diphenylpyrazolidine, by condensation of ethyl cyanoacetate with hydrazobenzene or by treatment of chloroacetylhydrazobenzene with potassium cyanide, opened the route to a parallel series of compounds which could also have physiological activity. The 4-ethyl homologue was synthesised similarly, but the 4-n-butyl homologue (c.f. phenylbutazone) could not be obtained by these synthetic routes. Further synthetic routes, including the attempted reductions of 4-butylidine-3-imino-5-oxo-1,2-diphenyl pyrazolidine and 4-butyroyl-3-imino-5-oxo-1,2-diphenyl pyrazolidine also failed to produce the 4-n-butyl homologue. Synthesis of 4-amino-3-imino-5-oxo-1,2-diphenyl-pyrazolidine, by reduction of the 4-isonitroso derivative, obtained by nitrosation of 3-imino-5-oxo-1,2-diphenylpyrazolidine, made possible the formation of condensed cyclic derivatives of the pyrazolidine. Condensation of the 4-amino derivative with ethyl chloroformate gave 4-carbethoxyanino-3-imino-5-oxo-1,2-diphenylpyrazolidine, which could not be cyclised to an iminazo-pyrazolidine, Nitrosation of the 4-amino derivative gave 4-azo-3-imino-5-oxo-1,2-diphenylpyrazolidine, Condensation of the 4-amino derivative with carbonyl chloride gave 4-carboxyamino- 3-imino-5-oxo-1,2-diphenylpyrazolidine, in preference to cyclisation to the iminazo-pyrazolidine. With glyoxal, the 4-amino derivative gave 5-oxo-1,2-diphenyl-3,4-pyrazino-pyrazolidine. The 4-amino derivative also self-condensed to give 2,3-5,6-di-(5-oxo-1,2-diphenylpyrazolidine-3,4)-pyrazine. With acetylacetone the 4-amino derivative gave 4-acetylaceton-amino-3-imino-5-oxo-1,2-diphenylpyrazolidine. Samples of some of the above materials were sent for testing for physiological activity, but as yet no results are available.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: G T Newbold
• Keywords: Organic chemistry, Pharmacology
• Date of Award: 1961
• Depositing User: Enlighten Team
• Unique ID: glathesis:1961-73584
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73584