Showing papers in "Advances in Heterocyclic Chemistry in 1974"

1,2,3-Triazoles

Abstract: Publisher Summary This chapter focuses on the chemistry of monocyclic1,2,3-triazoles as much of the chemistry of benzotriazoles and other fused systems has little in common with monocyclic triazole chemistry and provides a broad survey of methods of synthesis and reactions of triazoles. There has been considerable interest in 1,2,3-triazoles as light stabilizers and as optical brightening agents. They are also used as precursors for azapurines and similar heterocyclic systems that are potential carcinostatic agents. Three recognized classes of 1,2,3-triazoles are 1 H -, 2 H -, and 4 H -1,2,3-triazoles. Triazoles unsubstituted on nitrogen can be regarded either as 1 H - or as 2 H -derivatives, depending upon what tautomer is preferred. The first two classes can be regarded as aromatic systems whereas the third, the 4 H -system, cannot. This is reflected in the abundance of examples of 1 H - and 2 H -triazoles and the rarity of 4 H -triazoles. The thermal cycloaddition of azides to acetylenes is the most versatile route to 1 H -1,2,3-triazoles because of the wide range of substituents that can be incorporated into the acetylene and azide components. The base-catalyzed condensation of azides with activated methylene compounds is a well-established route to 1 H -triazoles and is the best route to triazoles bearing a 5-amino or hydroxy substituent and an aryl or carbonyl-containing function in the 4-position. The structure and spectroscopic and physical properties of triazole are discussed in the chapter.

Aromaticity of Heterocycles

Abstract: Publisher Summary This chapter discusses aromaticity of heterocycles. At a time when the validity of the concept of aromaticity is questioned, increasingly, it seems appropriate to review various definitions in common use and to survey their applications in heterocyclic chemistry. From a qualitative viewpoint the characteristics of an aromatic compound are easy to define. A compound is said to be aromatic if it is cyclic and unsaturated with an enhanced stability over simple olefinic compounds. The characteristic aromatic reactivity of the type described is clearly a matter of degree and is difficult to assess quantitatively. From a simple consideration of pyridine, which reacts less readily with electrophiles but more readily with nucleophiles at the ring carbon atoms than does benzene, it soon becomes apparent that attempts to discuss even relative aromatic character using kinetic criteria is fraught with difficulties; this is apart from the fundamental objection that chemical reactivity is not solely a function of ground-state stability.

Heteroaromatic N-Imines

Abstract: Publisher Summary This chapter discusses heteroaromatic N-imines. Amine N-imines are derived formally from tertiary amines by replacing the free pair of electrons by an imino group. Aliphatic, aromatic, or heteroaromatic compounds are obtained according to the nature of the amine. Heteroaromatic N-imines are derived from heterocyclic compounds containing an azomethine nitrogen atom in the molecule. General methods of preparation of heteroaromatic N-imines are beginning to be recognized, but they have not yet been widely applied. In addition, several special methods exist which have been used only for one specific heterocycle. Given this situation, the methods of preparation are classified in the chapter according to the parent heterocycle. The four most general methods of preparation are discussed in detail under the pyridine N-imines as this is where the experimental material is most extensive. A common method of preparation of heteroaromatic N-imines is the deprotonation of the corresponding N-aminoimmonium salts.

Base-Catalyzed Hydrogen Exchange

Abstract: Publisher Summary This chapter focuses on the base-catalyzed hydrogen exchange in heterocyclic compounds. Isotopic hydrogen exchange is becoming a widely employed method for preparing labeled compounds, being unsatisfactory only when the specificity of the process is uncertain and when the label can be replaced is high. A better understanding of the various factors involved in the preparation of labeled compounds as well as the stability of the label under widely different conditions is emphasized in the chapter. The conditions necessary to induce exchange vary widely and may be dictated by structural features. Proton-transfer reactions from heterocyclic compounds provide a favorable situation for the operation of a mechanism of exchange. Heterogeneous methods of exchange often involving expensive catalysts were widely used for incorporating tritium and deuterium into heterocyclic compounds. The isotopic exchange procedure is useful as a diagnostic tool for detection of minute traces of labeled compounds that can be seen in the recently developed method for assay of guanine residues in DNA. Many applications have resulted from studies of base-catalyzed isotope exchange reactions of heterocyclic compounds. Primary kinetic hydrogen isotope effects in the base catalyzed exchange of various heterocyclic compounds are tabulated in the chapter.

1,5-Benzodiazepines

Abstract: Publisher Summary This chapter discusses 1,5-Benzodiazepines. 1,5-Benzodiazepines are the 2,3-benzo-fused derivatives of the dihydrodiazepines. An alternative approach to the synthesis of benzodiazepines involves the reaction of β-chlorovinyl carbonyl compounds with o-phenylenediamine. In the first example methyl β-chlorovinyl ketone is used to obtain 5-methylbenzodiazepinium chloride. An extensive investigation has been made of the use of β-chlorovinylaldehydes for the preparation of 2,3-substituted benzodiazepines. Benzodiazepines and naphthodiazepines have also been prepared by addition and condensation of o-phenylenediamine, N-methyl-and N-phenyl-o-phenylenediamines, and 2,3-diaminonaphthalene with α-alkynyl ketones. Although the methylene signals of benzodiazepine bases appear as singlets at normal operating temperatures, at lower temperatures they give rise to double doublets. The results demonstrate that the benzodiazepine molecules take up boat conformations, which are, however, rapidly inverting at room temperature. Benzodiazepines and benzodiazepinium salts undergo ring contraction to give benzimidazoles when heated in aqueous solution. This presumably proceeds via ring-opening of the seven-membered ring to form a monoanil, with subsequent hydrolysis and ring closure to form a five-membered ring.

Recent Advances in the Chemistry of Dibenzothiophenes

Abstract: Publisher Summary This chapter discusses the chemistry of dibenzothiophene. Dibenzothiophene acts as a π-electron donor and readily forms complexes with known electron acceptors. Dibenzothiophene derivatives are thought to be present high-boiling crude oil distillates. It is believed that possible precursors of dibenzothiophenes in oil may be dihydroxybiphenyl derivatives formed from orthocoupling of phenols that are known to be present in crude oils. Dibenzothiophene derivatives have also been shown to be present in both light and heavy catalytic cycle oils and Middle East lubricating oils. Separation of dibenzothiophene derivatives from petroleum oil fractions has been achieved by integrated approaches in which fractionating processes such as isothermal distillation, vacuum fractionation, and molecular distillation have been combined with spectroscopic methods including mass spectrometry and NMR. Dibenzothiophenes have also been concentrated in sharp chromatographic fractions obtained, for example, by alumina gel percolation and have been detected by gas chromatography. The most important recent advance in the chemistry of dibenzothiophene has been the adoption of NMR techniques for structural determination.

2,3-Dihydro-1,4-diazepines

Abstract: Publisher Summary This chapter discusses 2,3-dihydro-1,4-diazepines. The first diazepine to be prepared, namely the 5,7-dimethyl derivative, is obtained by condensation of acetylacetone with ethylenediamine, and the reaction between β-dicarbonyl compounds and 1,2-diamines has remained the commonest method for the preparation of these compounds. Dihydrodiazepines are extremely stable compounds over a very wide range of pH and their hydrolysis may be ignored at high alkalinity. Bisoxoenamines, on the other hand, are readily hydrolyzed and at all but moderately alkaline pH the hydrolysis equilibrium is such that this condensation is effectively suppressed, leaving formation of the dihydrodiazepine to proceed without competition. At moderately alkaline pH, however, the bisoxoenamine is stable and furthermore precipitates from solution. Thus, its formation competes successfully with the alternative reaction and it is the predominant product. At higher temperatures the yields of bisoxoenamine drop sharply even at the most favored pH values. Almost identical results are found in reactions of other alicyclic or aliphatic diamines with acetyl-acetone.