Heterocyclic acids

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

Amides, prepared by condensation of tryptamine or substituted tryptamines with a large number of aliphatic, homocyclic, aromatic,and heterocyclic acids, have been used in the reaction. In few cases only did ring closure fail. ... 

However, it is among heterocyclic acids such as 2- and 6-hydroxy-pteridine that the most striking effects are observed. Rapid alkali... 

The pH-rate profile for the hydration of 2-hydroxypteridine at 20° shown in Fig. 4 is typical for the heterocyclic acids listed in Table VI. Some representative values of and are given in Table VII. The function plotted in the figure follows from Eq. (18), and the deviations... 

I 6 1 2CINO 3 Heterocyclic acid Anti-inilaramatory (53) W467... 

A number of heterocyclic acid amides in dilute hydrochloric acid are reduced to the aldehyde level where this is protected from further reaction as the dihydroxy... 

Another type of semisynthetic penicillins that are considered heteroylcarboxylic acid derivatives, in which the acyl group is represented as an aromatic heterocyclic acid derivative (oxacillin, cloxacillin, dicoxacillin). 

In a series of publications and patents,63 64 66"79 Wieniawski and coworkers reported the results of investigations of the reaction of sugar isothiocyanates with amines and various substituted hydrazides of heterocyclic acids. The reaction of isothiocyanate 2 with 2,6-diaminopyridine 81 was described,63 and the formation of dithioureide 82 as the sole product was observed. The... 

The pKa values of diazines have been used to calculate aza substituent constants, and from these, with a fair but not complete measure of success, the basicities of substituted pyridines and the strengths of heterocyclic acids can be predicted.33,34... 

The Arndt-Eistert reaction is a comparatively simple method for converting an acid into its next higher homologue, or to a derivative of the homologous acid, such as an amide or an ester. The reaction is applicable to aliphatic, aromatic, alicyclic and heterocyclic acids, and the yield is generally good. 

Of lesser relevance to this discussion are halogenation methods involving the modification of the carbon skeleton (synthesis and degradation). The Hunsdiecker reaction, as applied to certain heterocyclic acids, has had limited application for the synthesis of halogen derivatives. The preparation of 3-bromo-4,6-dimethyl-2-pyridone from the silver salt of the respective 3-carboxylic acid by treatment with bromine in carbon tetrachloride is a rare example of success.13 The interaction of carbenes with heterocycles also has been employed infrequently, but recent advances in carbene generation may reactivate this approach.14 The Ciamician-Dennstedt ring expansion of pyrrole to / -halopyridines is a case in point18 [Eq. (4)] ... 

This valuable method for the conversion of an acid to its next higher homolog has been used to prepare aliphatic, aromatic, and heterocyclic acids. Excellent reviews of the reaction have been published. Diazomethane preparations are described elsewhere (method 500). The acyl chloride is added to an excess of diazomethane in ether or benzene solution. Diazoketones are usually not purified. 

It should be noted that some data on complexation of transuranium elements with various N-donor ligands, such as azide ion, isothiocyanate ion, amine-N-polycarboxylic and heterocyclic acids, 8-hydroxyquinoline and its derivatives, were published as early as 1950-1970 [42-77], The quantitative parameters of complexation (number and composition of complexes, stability constants, thermodynamic parameters) were determined using accessible at that time methods (spectrophotometry, potentiometry, ion exchange, solvent extraction). It was shown that transuranium elements in different oxidation states can form complexes with N-donor ligands. However, only presumptive conclusions regarding structure of complexes were drawn at that time,... 

Application of this method to heterocyclic acids permits easy preparation of acid chlorides previously requiring special procedures. Thus 5-methyl-3-isoxazole-carbonyl chloride was initially obtained only by the reaction of the sodium salt of the acid with phosphorus pentachloride" or with thionyl chloride the free acid does not react with thionyl chloride alone. An improved procedure is as follows."... 

Although esters are sufficiently unreactive to permit selective reductions such as those described, esters of aliphatic, aromatic, and heterocyclic acids can be reduced in varying degree with a large excess of sodium borohydride in methanol."... 

Quinoline 1-oxide can be substituted by mercaptans with the 3-isomer being the major product.Heterocyclic acid amides, such as lO-methyl-9-acridone and 2-methyl-l-phthala-zone, were aminoalkylated by ClMg(CHa)sNMe3. The carbinols formed have the character of pseudo bases and were transformed to the corresponding acridinium or phthalazinium salts. ... 

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