Pteridines, amino-, tautomerism

Brown and Jacobsen demonstrated by ultraviolet spectral comparisons that 2-amino-(3H)-pteridin-4-one was the predominant tautomeric form. The evidence in favor of 4-amino-(lH)-pteridin-2-one is less conclusive, but, nevertheless, convincing. 

Tautomerism is common in pteridine derivatives and the favored tautomers should be represented by the structural formulas. Amino groups exist as such and not in the iminodihydro form whereas the hydroxy and thiol functions 9 located adjacent or para to a ring nitrogen atom prefer the thermodynamically more stable amide (lactam) and thioamide (thioxo) configuration 8 (Scheme 1) . 

Six-six condensed heterocyclic systems without a tautomeric functional group(s) [for instance, pteridine 135 (R = R2 = R4 = H)], do not exhibit prototropic tautomerism. The introduction of an oxo(thioxo)- and/or amino group(s) into the pteridine system, and the appearance of at least one NH group in the ring, leads to functional and/or annular tautomerism. Pteridine is formally the parent of three groups of compounds of particular interest because of their biological importance pterins (136), lumazines (137), and flavins (138). 

Pteridines behave electrochemically akin to quinoxaline [364], with the pyrazine ring being reduced the 3,4-double bond may be hydrated akin to quinazoline [314, 364]. In the first, reversible step of 6-methyl-2-amino-4(3i/)-pteridone (LXVII R = H), a 5,8-dihydro derivative (LXVIII) is formed, which in a pH-dependent reaction tautomerizes into the more stable 7,8-dihydro compound (LXIX) LXIX is reduced in acidic and neutral solution to the 5,6,7,8-tetrahydro derivative (LXX), which may be oxidized to a quinonoid dihydro compound (LXXI) LXIX is formed on tautomerization of LXXI [365, 366] ... 

Pteridinamines, -ones and pteridinethiones show tautomeric features which are similar to those of other 7r-electron deficient A-heterocycles. The pteridinamines show a marked preference for the amino 3,5 (X = NH) rather than the iminohydro 4,6 (X = NH) form, but, with few exceptions, hydroxy and sulfanyl pteridines show a strong preference for tautomers 4,6 (X = O or S) in which the mobile proton is situated at the adjacent ring nitrogen atom. 

Even though pteridinamines exist in their amino and not as their tautomeric imine forms, they usually alkylate on ring nitrogen, although the products may undergo subsequent Dimroth rearrangement274 276 to yield alkylaminopteridines. However, trimethylsilylation normally results in the formation of (trimethylsilylamino)pteridines directly (see Section 7.3.1.4.3.1.). 

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