Pteridines Addition reactions

Studies on covalent hydration of N-heterocycles (67AG(E)919,76AHC(20)117) have revealed the diagnostic value of alkyl substituents in structural assignments due to their steric hindrance effects in addition reactions. C-Methyl substituents are therefore also considered as molecular probes to solve fine-structural problems in the pteridine field. The derivatives... 

The action of sulfur nucleophiles like sodium bisulfite and thiophenols causes even pteridines that are unreactive towards water or alcohols to undergo covalent addition reactions. Thus, pteridin-7-one smoothly adds the named S-nucleophiles in a 1 1 ratio to C-6 (65JCS6930). Similarly, pteridin-4-one (73) yields adducts (74) in a 2 1 ratio at C-6 and C-7 exclusively (equation 14), as do 4-aminopteridine and lumazine with sodium bisulfite. Xanthopterin forms a 7,8-adduct and 7,8-dihydropterin can easily be converted to sodium 5,6,7,8-tetrahydropterin-6-sulfonate (66JCS(C)285), which leads to pterin-6-sulfonic acid on oxidation (59HCA1854). 

The use of carbon nucleophiles in Michael-type addition reactions with pteridine and its derivatives leads to a quite complicated and divergent pattern. These reactions are strongly dependent on the nature of the carbon nucleophile and can be divided into various categories. 

Pteridine, 6-aIkyIthio-2,4-diamino-reactivity, 3, 299 Pteridine, 2-amino-acylation, 3, 295 hydrolysis, 3, 293, 294 Michael addition reactions, 3, 279, 288 structure, 3, 267 Pteridine, 4-amino-acylation, 3, 295 hydrolysis, 3, 293, 294 3-oxide... 

Michael addition reactions, 3, 279, 288 structure, 3, 273 Pteridine-4-thiones synthesis, 3, 318... 

In heterocyclic chemistry it can be misleading to speak of covalent addition to mean both a product of an addition reaction, such as the hydration of a neutral substrate (i.e., transformation of pteridine to the 4-hydroxydihydro derivative),20 and a product of an attachment reaction, such as the reaction of the hydroxide ion with the ring carbon of a heteroaromatic cation.21... 

Pteridines also undergo nucleophilic addition reactions particularly easily, including covalent hydration, addition of bisulfite and others. 

Pteridine Studies. Part XXX. Some Michael-type Addition Reactions of 7-Hydroxypteridine. 

Pteridine Studies. Part XXXII. Nucleophilic Addition Reactions of 2-Amino-pteridine. 

Pteridine Studies. Part XXXIV. Nucleophilie Addition Reactions of Pteridine-... 

Pteridine Studies. Part XLII. Additive Reactions between Alcohols and Pteridines. 

The 7t-electron deficiency of pteridine should greatly aid nucleophilic substitution, but complications arise because of the ready nucleophilic covalent addition reactions referred to previously. However, nucleophilic displacement of halo substituents occurs very easily, except in the presence of electron-donating groups such as amino, etc. Increasing the number of such substituents increases the difficulty of carrying out nucleophilic substitutions. The kinetics for the aminolysis of 2,4,6,7-tetrabromopteridine shows that the order of reactivity for bromo substituents is 7 > 6 > 2 > 4.30,19 It is probable that 2,4,6,7-tetrachloropteridine shows the same pattern of reactivity and that generally bromo- and chloropteridines react similarly. 

---