Nitrogen Containing Heterocyclics

Mills and Smith (504) were the first, in 1922, to develop a systematic study of the reactivity of methyl groups fixed on nitrogen-containing heterocycles. While in alkylpyridines the 2- (or 6) and 4-positions are activated, only the 2-position in thiazole corresponds to an enhanced reactivity of the methyl groups in condensation with aldehydes 4- and 5-methylthiazoles bear inert methyl groups. Quatemization of the thiazole nitrogen enhances still further the reactivity of the methyl in the 2-position (cf. Chapter IX), but it does not increase the reactivity of a methyl group in the 4-position (504). The authors invoke the possibility for 2- (and 6) methylpyridine and 2-methylthiazole to pass, to some extent, into the reactive enamine form (245), while 4-methylthiazole could adopt such a structure only with the participation of an unusual formula such as 247 (Scheme 112). 

It is well known that in nitrogen-containing heterocyclic compounds the reactivity of alkyl groups is enhanced. In the thiazole series, alkyl groups in the 2-position are reactive towards carbonyl compounds and condensations may be realized. 

Two nitrogen containing heterocyclic aromatic compounds—pyrimidine and purine— are the parents of the bases that constitute a key structural unit of nucleic acids... 

Dipolar cycloaddition reactions with azides, imines, and nitrile oxides afford synthetic routes to nitrogen-containing heterocycles (25—30). 

I. D. Sadekov and V. I. Minkin, Tellurium-Nitrogen Containing Heterocycles, Adv. Heterocycl. Chem., 79, 1 (2001). 

Their Esters with Nitrogen-Containing Heterocyclic Compounds... 

Dimethyl acetylenedicarboxylate gave first a similar adduct (2) which then added further molecules of furan yielding (3) and subsequently (4). Between 1931 and 1940 the reactions of acetylenedi-carboxylic acid and its dimethyl ester with a number of nitrogen containing heterocyclic compounds were examined, and structures were proposed for the products. Apart from an unpublished investigation of the products from pyridine and dimethyl acetylenedicar-... 

III. Reactions of Acetylenic Acids and Esters with Individual Nitrogen-Containing Heterocyclic Compounds... 

Reversible covalent hydration across C=N bonds occurs in a number of nitrogen-containing heterocycles, including pteridine and its 2- and 6-hydroxy derivatives, quinazoline (as the cation), and 1,4,6-triazanaphthalene (as the cation). Among bases giving this reaction, the neutral molecule exists predominantly as the anhydrous form, whereas the cation contains an increased proportion of the... 

Similar considerations apply to nitrogen-containing heterocycles carrying acidic groups, for example 2-hydroxypteridine, but the situation is further complicated by lactam-lactim tautomerism in the neutral species. Thus, hydroxypteridines exist predominantly as lactams, such as 6, in dynamic equilibrium with small amounts of lactims, such as 7. There is, in consequence, a decrease in the aromatic... 

The reversible hydration of nitrogen-containing heterocyclic bases and their hydroxy and mercapto derivatives is acid-base catalyzed and, at constant pH, the reactions obey first-order rate equations. 2 26.27-33... 

Tables V and VI contain all the equilibrium constants so far reported for nitrogen-containing heterocycles that undergo reversible covalent hydration. Table V comprises equilibria involving hydration in cations and neutral molecules, and Table VI deals with systems of neutral molecules and anions.

The 4-unsaturated-5-oxazolones provide convenient starting materials for the synthesis of other nitrogen-containing heterocyclic systems. The preparation of tetrazoles and isoquinolines is discussed in Sections II,B, 1 and II,B,2,b. 

A. B. Sheremetev and P. I. Broydo, in V All-Union Symp. Chem. Nitrogen Contain. Heterocycl. Compd., Abst. Book, Chernogolovka, USSR, 1991, 226 (in Russian). 

O. V. Kharitonova, A. B. Sheremetev, andT. S. Novikova, in The Vth All-Union Conference on Chemistry of Nitrogen Containing Heterocyclic Compounds., Oetober 22-25, 1991, Chernogolovka, USSR, 227 (in Russian). 

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