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Durham e-Theses
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An investigation of the chemistry of cinnolines

Atkinson, Charles W. (1948) An investigation of the chemistry of cinnolines. Doctoral thesis, Durham University.



Earlier work which has resulted in the synthesis of cinnolines is reviewed. The strictly historical approach has been modified to accommodate a classification based upon the type of cinnoline involved. Preparative routes to 4-chloro-2-amlnoacetophenone are described. Reaction between the acid chloride of 4-chloro-2- phthallmldobenzoic acid and diethyl sodiomalonate followed by hydrolysis gives the pure amine via the acetamido-compound. A second route which utilises 4-chloro-2-nitrobenzovl chloride and ethyl sodioacetoacetate leads to 4-chloro-2-nitroaceto-phenone and thence to the amine, Diazotisation of 4rohloro-2-aminoacetophenone and subsequent ring closure produces 7-chloro-U-hydroxycinnoline.Nitration of 4-Ghloro-2-acetamidoacetophenone has given the 5-nitro-derivatlve with some of the 3-nitro-isomer. Hydrolysis to the corresponding nitro-amines and diazotisation of these in sulphuric acid yields 6-nitro-7-chloro- and 8-nitro-7-chloro-U-hydroxycinnoline. In hydrochloric acid, however, the corresponding dichloro-4-hydroxycinnolines are formed, the replacement (nitro →chloro) taking place before cyclisation to the cinnoline. Attempts to prepare 4-chloro-2-aminopropiophenone are described, and work on the projected synthesis of 7-methoxy-4-hydroxyclnnoline is reported. Widman's synthesis of 7-methylcinnoline-7-carboxylic acid has been repeated; in general, the original results are confirmed but the acid is best purified via the ethyl ester. 4-Methylcinnoline and the 6- and 7-chloro-compounds have been prepared by ring closure of the diazotised o-isopropenylanilines; these are formed by dehydration of the corresponding carbinols which arise from the o-amino-acetophenones or methyl anthranilates by a Grignard reaction. The 4-methylcinnolines are characterised by their green picrates and red ethiodldes. The application of a wide variety of reactions to estimate the reactivity of the methyl group in 4-methyl-cinnoline has had little success. Confirmation of enhanced reactivity and hence of the postulate that is N(_1) the basic centre of the molecule is provided by the formation of 4-p-dimethylaminostyryl-l-ethylcinnollnlum iodides. Reduction of a number of cinnolines with sodium and alcohol has been carried out. Qualitative examination has shown partial conversion to the corresponding indoles of 4-(4'-hydroxyphenyl)oinnoline, the 3-methyl compound and of 3-methyl-4-P-anisylclnnollne; 3-phenyl-4-p-anisylcinnoline and the deraethylated compound are virtually unchanged. 4-Methylclnnoline and its 6- and 7-chloro-derivatives all give 3-niethylindole as the final-product but data on the intermediate stages is incomplete. Estimation of the ammonia liberated in each case confirms the above findings. Attempts to repeat Stolle and Becker's synthesis of 3-phenylcinnoline-4-carboxylio acid are reported.

Item Type:Thesis (Doctoral)
Award:Doctor of Philosophy
Thesis Date:1948
Copyright:Copyright of this thesis is held by the author
Deposited On:13 Nov 2013 16:09

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