Pyrimidine reactivity

A useful discussion of the metallation of pyrimidines is to be found in a more general review on metallation <06EJO1593>. A full issue of Chemical Reviews was concerned with DNA damage and repair, parts of which may be of interest relating to pyrimidine reactivity... 

Nucleophilic substitution of leaving groups is probably the most important area in pyrimidine reactivity and, in particular, the differential reactivity of C-2 and C-4 is the most investigated topic. The displacement of 2- and 4-sulfide and sulfone groups is referred to in the synthesis section. The selective hydrolysis of 4-amino-2-chloropyrimidines under acidic conditions has been studied in great detail by a process research group <06OPRD921>. 

Pyrimido[4,5-J]pyrimidine-5,7-diones synthesis, 3, 363 Pyrimidopyri mi dines synthesis, 4, 507 Pyrimido[ 1,2-a]pyrimidines reactivity, 3, 348 structure, 3, 337-338 synthesis, 3, 360 Pyrimido[ 1,6-fl]pyrimidines reactivity, 3, 349 structure, 3, 338 synthesis, 3, 362 Pyrimido[l, 6-c]pyrimidines reactivity, 3, 349 structure, 3, 338 synthesis, 3, 362 Pyrimido[4,5-d]pyrimidines applications, 3, 368 cleavage, 3, 350 reactions... 

Ring- or side-chain fluoriaated nitrogen heterocycHcs have been iacorporated iato crop-protection chemicals, dmgs, and reactive dyestuffs. Key iatermediates iaclude fluoriaated pyridines, quiaolines, pyrimidines, and tria2iaes. Physical properties of some fluoriaated nitrogen heterocycHcs are Hsted ia Table 13. 

Much of the reactivity shown by the ring atoms and substituents of pyrimidine is akin to that of the corresponding parts of 1,3-dinitrobenzene and 3-nitropyridine. This arises from the quantitatively similar electron-withdrawing effects of doubly-bound ring nitrogen atoms and of nitro groups in reducing sharply the aromaticity of the cyclic system. 

There are few reports on the reactivity of aryl substituents attached to pyrimidine or quinazoline. However, nitration may be carried out with some success. 

The action of alkyllithiums and alkylmagnesium halides with functional groups on pyrimidines has been mentioned in appropriate sections on the reactivity of the substrates. 

Imidazo[l,2-c]pyrimidine, 2,5,7-trichloro-nucleophilic displacement reactions, 5, 627 Imi dazo[ 1,2-a]pyrimidines pK, 3, 338 reactivity, 5, 627 synthesis, 5, 647 Imidazo[ 1,2-c]pyrimidines reactions, 5, 627 structure, 5, 610 synthesis, 5, 648-649 lmidazo[ 1,5-a]pyrimidines reactions, 5, 628 synthesis, 5, 649 lmidazo[l,5-6]pyrimidines synthesis, 5, 649-650 Imidazopyrrolopyridines bromination, 4, 506 lmidazo[4,5-6]quinoxaline nomenclature, 1, 22... 

Pyrimidin-5-amine, 4-methylamino-synthesis, 3, 121 Pyrimidin-5-amine, 4-oxo-purfne synthesis from, 5, 582 Pyrimidinamines acylation, 3, 85 alkylation, 3, 86 basic pXa, 3, 60-61 diazotization, 3, 85 Dimroth rearrangement, 3, 86 electrophilic reactions, 3, 68 Frankland-Kolbe synthesis, 3, 116 hydrolysis, 3, 84 IR spectra, 3, 64 N NMR, 3, 64 nitration, 3, 69 Principal Synthesis, 3, 129 reactivity, 3, 84-88 structure, 3, 67 synthesis, 3, 129 Pyrimidin-2-amines alkylation, 3, 61, 86 basic pK , 3, 60 diazotization, 3, 85 hydrogenation, 3, 75 hydrolysis, 3, 84 mass spectra, 3, 66 Pyrimidin-4-amines acidity, S, 310 alkylation, 3, 61, 86 basic pXa, 3, 61 Schifi base, 3, 85 synthesis, 3, 110, 114 1,3,5-triazines from, 3, 518 Pyrimidin-5-amines basic pXj, 3, 61 hydrogenation, 3, 75 reactions... 

Pyrimidine, 2-methylthio-5-nitro-aminolysis, 3, 96 Pyrimidine, nitro-reactivity, 3, 84-88 synthesis, 3, 130 Pyrimidine, 3-nitro-synthesis, 2, 504 Pyrimidine, 5-nitro-cation... 

The pyridine family of heteroaromatie nitrogen compounds is reactive toward nueleophilie substitution at the C-2 and C-4 positions. The nitrogen atom serves to aetivate the ring toward nueleophilie attack by stabilizing the addition intermediate. This kind of substitution reaction is especially important in the ehemistiy of pyrimidines. 

The halogen atom in benz-chloro substituted quinazolines is very stable (as in chlorobenzene), whereas the halogen atoms in positions 2 and 4 show the enhanced reactivity observed with halogen atoms on carbon atoms placed a and y to heterocyclic ring nitrogens. The chlorine atom in position 4 is more reactive than in position 2, and this property has been used to introduce two different substituents in the pyrimidine ring. ... 

With unsymmetrical diketones the orientation of the reaction is again controlled by the reaction of the most reactive carbonyl group with the 5-position of the pyrimidine ring. Thus, benzoyl acetone and 6-aminouraoil gave 5-methyd-7-phenylpyrido[2,3-d]pyrimidine-2,4-(lH,3iI)-dione (71), in preference to the 5-phenyl isomer (72). ... 

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