Pyridine Pyrimidines

Table 9 Approximate Positions of Ring-stretching Modes for Pyridines, Pyrimidines and Benzenes (cm )...

All these methods demonstrate that the 2-positions of pyridine, pyrimidine, and other azines are the most electron deficient in the ground state. However, considerably greater chemical reactivity toward nucleophiles at the 4-position is often observed in syntheses and is supported by kinetic studies. Electron deficiency in the ground state is related to the ability to stabilize the pair of electrons donated by the nucleophile in the transition state. However, it is not so directly related that it can explain the relative reactivity at different ring-positions. Certain factors which appear to affect positional selectivity are discussed in Section II, B. 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

First we consider diacetylene transformations leading to fundamental heterocycles (pyrroles, thiophene, selenophene, tellurophenes, pyrazoles, isoxazoles, pyridines, pyrimidines). Then cyclization reactions involving 1-heterobut-l-en-3-ynes, 4-heterobut-3-en-2-ones, and 4-heterobut-3-yn-2-ones (91UK103 92KGS867 00UK642) as diacetylene equivalents are discussed. 

This pyridine-pyrimidine ring transformation has also been observed on treatment of 2-bromoquinoline with potassium amide in liquid ammonia, 2-methylquinazoline being obtained (67RTC187). Similarly, 8-bromo-l,7-phenanthroline gives 2-methyl-l,3,5-triazaphenanthrene (83JHC447)... 

Amide-induced pyridine-pyrimidine transformation is also reported with 2-bromo-l, 5-naphthyridine. 2-Methyl-4-amino-l, 3,5-triazanaphtha-lene is obtained, together with its 4-amino derivative The presence of the amino group at position 4 is certainly due to a SnH amino-dehydrogenation in preformed 2-methyl-l,3,5-triazanaphthalene (63RTC997, 73RC459, 94MI1). 

Petitjean A, Lehn JM (2007) Conformational switching of the pyridine-pyrimidine-pyridine scaffold for ion-controlled FRET. Inorganica Chim Acta 360 849-856... 

Section 4.2.1 will be devoted to heterocycles, section 4.2.2 will cover other kinds of protomeric tautomeric equilibria (e.g., enol/ketone, formic acid, formamidine, etc.), and section 4.2.3 will discuss an example of a ring/chain tautomeric equilibrium. The order of presentation will be approximately by increasing molecular weight within each section. A review by Kwiatkowski et al. [267] covers work on formamide, pyridines, pyrimidines, purines, and nucleic... 

R.W. Millar, S.E. Philbin, R.P. Claridge, J. Hamid, Studies of novel heterocyclic insensitive high explosive compounds pyridines, pyrimidines, pyrazines and their bicyclic analogues . Propellants Explos. Pyrotech. 81—92. 

In contrast, some substituted anilines, e.g. 2-nitroaniline,143 2-chIoro-4-(trifluoromethyI)ani-Iine,143 benzene-1,3-diamine,150 or 4-chlorobenzene-1,3-diamine,150 give only very low yields of product or formed tars under the fluorination conditions. The diazotization followed by in situ fluorodediazoniation of the corresponding diazonium salts have been systematically studied in hydrogen fluoridc/base solutions of different composition to ascertain the most important influences on the reaction.329 Besides numerous examples of substituted anilines, various derivatives of pyridine, pyrimidine, 1.3,5-triazine, and benzthiazole have been included in these investigations (yields 45—99%). 

Despite the numerous studies devoted to the synthesis of five-membered ring heterocycles using enamines as synthons, most publications on the use of enamines in the synthesis of heterocycles deal with six-membered heterocyclic ring systems, especially pyridine, pyrimidine, and pyran derivatives. 

The properties of 1,3-oxazinium salts are similar to those of pyrylium salts.4194,219,255-259 1,3-Oxazinium salts are intermediates for the synthesis of derivatives of pyrazole, isoxazole, pyridine, pyrimidine, quinoline, isoquinoline, chromene, benzopyrylium salts, butadiene, etc.4... 

There remains the choice of Up values. As a starting point we have adopted Uc = —9.5 eV, which is known to give satisfactory values for the ionization potentials in hydrocarbons86 and determined U0, Ux, UNH> and t/NHl so as to reproduce the ionization potentials of formaldehyde, pyridine, pyrimidine, pyrrole, and aniline. Moreover,... 

The negative charge in a Meisenheimer complex, can be stabilized not only by a nitro substituent at one of the charged atoms, but also by a ring nitrogen. Therefore, pyridines, pyrimidines, and 1,3,5-triazines containing a Cl atom in the 2-, 4-, and/or 6-position, likewise enter into Ar-SN reactions via Meisenheimer complexes very readily. 

N. V Alekseeva, L. N. Yakhontov, Reactions of Pyridines, Pyrimidines, and 1,3,5-Triazines with Nucleophilic Reagents, Russ. Chem. Rev. 1990, 59, 514-530. 

The monofunctional complexes [PtCl(dien)]+, [PtCl(NH3)3]+, and the active d.v-compounds cA-[PtCl(NH3)2 (Am)]+, where Am is an heterocyclic or aromatic amine ligand like pyridine, pyrimidine, purine, or aniline, only form stable monoadducts with DNA [50][51]. However, when Am = A-methyl-2,7-diazapyrenium (a strong intercalator), the monoadduct is stable only on single-stranded DNA. On double-stranded DNA it is hydrolyzed with release of c T-[Pt(NH3)2(Am)(H20)]3+ or of Am generating the aqua monoadduct of cisplatin [52],... 

A 13C—NMR study of several dimethylamino derivatives of pyridine, pyrimidine, and 2-oxopyrimidine with and without o-methyl substitution indicates a progressive twist of the dimethylamino group in hindered derivatives (78JCS(P2)1119). Unfortunately, the barriers have not yet been determined. The free energy of activation for 4-(Af-methylamino)pyridine (80JCS(P2)1704) is AG = 42.6 kJ mol-1 and is close to that of N-methyl-4-nitroaniline. 

Table 22 Approximate positions of ring-stretching modes for pyridines, pyrimidines, and benzenes (cm 1)...

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