ERRATUMTo the article "4-Hydroxy-2-quinolones. 179. Synthesis, Structure, and Anti-inflammatory Activity of 4-Hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-ylacetic Acid and its Derivatives" -I.
The reaction of ethyl 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate with p-toluenesulfonylhydrazide in anhydrous solvents in the presence of triethylamine results in the tosylation of position 4 of the quinolone. Features of the steric structure of the tosyl-substituted compound are discussed.
The reactions of activated hetaryl halides with p-toluenesulfonylhydrazide and subsequent basic hydrolysis of the intermediate β-N-hetarylhydrazides formed is generally a well known method for the exchange of halogen in a heterocycle for hydrogen [2,3]. The yields are not always high but the simplicity of carrying out the experiment and the possibility of performing it with substances containing different reducing groups often warrants such a route.We have previously unsuccessfully attempted to modify the 1-R-4-chloro-2-oxo-1,2-dihydroquinoline-3-carboxylate esters 1a,b to the corresponding 4H-derivatives by direct reductive dehalogenation in the system zinc-glacial acetic acid [4]. At the same time we have repeatedly noted the ease with which the chlorine atom in such compounds is substituted by N-nucleophiles with a simultaneous inertness of the ester component [5][6][7]. It is therefore quite logical to propose an indirect method of exchanging the chlorine for hydrogen in the esters 1a,b involving an initial synthesis of the β-N-hetaryl-substituted tosylhydrazides 2a,b which might then be converted to the 2-oxo-1,2-dihydroquinoline-3-carboxylic acids or their ethyl esters with a standard basic hydrolysis.It was found that the 4-chloro-substituted esters 1a,b in refluxing 96% ethanol and in the presence of triethylamine actually quite readily reacted with p-toluenesulfonylhydrazide. However, the 1 H NMR spectra gave an unexpected result. The compounds obtained did not contain a p-toluenesulfonyl fragment in its structure. The ethoxycarbonyl groups which are normally stable under analogous conditions [5,6] together with the halogen atom (negative Beilstein test) were also absent. In their place there appeared at low field two singlets, each of intensity 1H, which could be identified from their chemical shift as due to NH or OH group protons.
Keywords: 2-aminopyrimidine, 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides, bromination, antitubercular activity, X-ray structural analysis.Pyrimidine bases occur in a number of the most widespread heterocyclic systems in nature. Occurring in nucleic acids and coenzymes these compounds play a direct role in encoding and transmitting hereditary information, in the metabolism of carbohydrates and lecithin, and also in many biochemical processes important for animals and plants [2]. As a result, natural pyrimidines have an extremely broad spectrum of biological activities: from vitamins and regulators of biosynthesis amongst specific living organism proteins to antibiotics and alkaloids and to tetrodotoxin [3] which is one of the most powerful non-protein neurotoxins. Of course, pharmaceutical chemistry has not stood aside from the facts listed. As a result, to this day around 100 synthetic preparations [4] based on pyrimidine have been created and indeed used in medicinal practice. The majority of them fit into four broad categories of well known substances: barbiturates, sulfanilamides, antimicrobial pyrimidine-2,4-diamines, and antitumor agents [3]. Less impressive but none the less valuable for public health are such pharmacological groups as diuretics, antihypertensive and antihistamine agents, anticonvulsants, vitamins etc. [3,4].
Keywords: 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinolines, acetoacetic ester, hydrazides, hydrazones, 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids, antitubercular activity, X-ray structural analysis.In a study of the biological properties of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids hydrazides it was found that their high antitubercular activity almost totally disappeared in their thermolysis products, i.e. the symmetrical N,N'-di(1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)hydrazines. It was proposed that the main reason for this effect was basically the sharp lowering of the solubility of the N,N'-diacylhydrazines in water and in organic solvents [2]. Attempts to confirm or to contradict this proposal are the subject of this publication.For a proper resolution of the stated problem it would be necessary to investigate substances which, on the one hand, were close in structure to the reported N,N'-diacylhydrazines while (at the same time) not belonging to them and, on the other hand, differing significantly from them in solubility (in a worse direction). In our view, one rather readily achieved practical route for reaching this target may be a change from diacylhydrazines to acylhydrazones. As a rule such compounds are poorly soluble in the majority of organic solvents and this property is frequently used in analytical chemistry. However, in order to adhere to the second requirement of structural similarity one of the acyl fragments in the N,N'-diacylhydrazines should not simply be exchanged with any kind of aldehyde or ketone but needs to contain a 4-hydroxy-2-oxoquinoline ring. In particular an extremely suitable example of such ketones is the 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline (1).
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