Heterocyclic compounds, basicity

Thiurets — see 1,2,4-Dithiazolidines, diimino-Thonzylamine antihistamine, 3, 153 Thorpe reaction benzothiophenes from, 4, 876 Thorpe-Ziegler cyclization, 2, 74 Three-membered heterocyclic compounds basicity, 7, 23... 

Nonaromatic heterocyclic compounds piperidine for example are similar m basic ity to alkylamines When nitrogen is part of an aromatic ring however its basicity decreases markedly Pyridine for example resembles arylammes m being almost 1 mil lion times less basic than piperidine... 

The reactions of carbenes, which are apparently unique in displaying electrophilic character in strongly basic solutions, include substitution, addition to multiple bonds, and co-ordination with lone pairs of electrons to form unstable ylides. This last reaction is of obvious relevance to a consideration of the reactions of heterocyclic compounds with carbenes and will be summarized. 

The Chemistry of Heterocyclic Compounds has been published since 1950 under the initial editorship of Arnold Weissberger, and later, until his death in 1984, under the joint editorship of Arnold Weissberger and Edward C. Taylor. In 1997, Peter Wipf joined Prof. Taylor as editor. This series attempts to make the extraordinarily complex and diverse held of heterocyclic chemistry as organized and readily accessible as possible. Each volume has traditionally dealt with syntheses, reactions, properties, structure, physical chemistry, and utility of compounds belonging to a specihc ring system or class (e.g., pyridines, thiophenes, pyrimidines, three-membered ring systems). This series has become the basic reference collection for information on heterocyclic compounds. 

In practical terms, it is invariably a nitrogen atom that is protonated in salt formation. This always leads to a downfield shift for protons on carbons both alpha and beta to the nitrogen concerned. In alkyl amines, the expected shifts would be about 0.7 and 0.3 ppm respectively. Remember that some heterocyclic compounds (e.g., pyridine) contain nitrogen atoms that are basic enough to protonate and comparable downfield shifts can be expected (Spectrum 5.9). 

These examples of the use of microwave irradiation in the synthesis of heterocyclic compounds show the great versatility of this technique, which can be used under a variety of experimental conditions. Even when there is no improvement of yields, or rates, or specificity, the technique is worthwhile owing to its simplicity. It can be foreseen that microwave ovens are going to be among the basic equipment of research laboratories in the near future. Combinatorial and parallel synthesis under the action of microwave irradiation is becoming a powerful tool for discovery of new molecules and should develop very rapidly. 

Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nudeic add constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH]... 

Oxidative rearrangements resulting in the formation of heterocyclic compounds are relatively less explored, although some of them are quite important. A basic reaction is the conversion of a chalcone to 3,3-dimethoxy-l-phenylpropanone (Eq. 2) (85TL2961). This process may be adapted to heterocyclic synthesis. 

The synthesis of isoxazolines and pyrazolines via the Michael addition of hydro-xylamine and phenyl hydrazine to chalcones and related enones was also reported with activated Ba(OH)2 as a basic catalyst (293) (Scheme 45). In both cases, reactions were performed at reflux of ethanol, and excellent yields (65-80%) with 100% selectivity to the heterocyclic compounds were observed. Steric hindrance associated with the carbonyl compound as well as the electronic character of the substituents in the aromatic ring slightly affected the yields of the heterocyclic compounds. 

Stocks, P. G. and Schwarz, A. W. (1982). Basic nitrogen-heterocyclic compounds in the Murchison meteorite. Geochim. Cosmochim. Acta, 46, 309-15. 

In the majority of dehydration reactions, heterocyclic compounds are formed, rather than carbocyclic compounds. Many possibilities for formation of carbocyclic compounds exist, but these are important only if (a) the heterocyclic or acyclic tautomers cannot undergo further elimination reactions, or (b) the conditions of reaction greatly favor the formation of an acyclic tautomer capable of affording only the carbocyclic compound. Both five- and six-membered carbocyclic compounds have been isolated, with reductic acid being the compound most frequently reported. Ring closure occurs by an inter-molecular, aldol reaction that involves the carbonyl group and an enolic structure. Many examples of these aldol reactions that lead to formation of carbocyclic rings have been studied.47 As both elimination and addition of a proton are involved, the reaction occurs in both acidic and basic solutions. As examples of the facility of this reaction, pyruvic acid condenses spontaneously to a dibasic acid at room temperature in dilute solution, and such 8-diketones as 29 readily cyclize to form cyclohexenones, presumably by way of 30, either in acid or base. 

A group of Italian workers from Modena, led by Professor Taddei, has reviewed published work on the conformations of acyl groups in heterocyclic compounds, including both C-acyl and N-acyl derivatives. The first recent review of the basicity and acidity of azoles, covering both gas-phase and solution measurements, is presented by a group of Spanish workers (Catalan et al.). H. Weber has summarized the considerable recent progress in oxidative transformations of heteroaromatic iminium salts. 

Allenyl- and propargyl-phosphonium salts have also been used as precursors of heterocyclic compounds in the presence of various functionalized nucleophiles279, via the intermediacy of vinylphosphonio compounds however, an ylide extrusion has been sometimes observed815,816, depending on the nature of the functions in the nucleophile (reaction 250). Allenylphosphonium salts are able to add such weak CH acids as in ketones, even in absence of basic catalysts817,818, without any modification of the keto group (reaction 251). 

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