Methylpteridine

Excess of bromine converts each methylpteridine compound into the dibromomethyl derivative which on hydrolysis gives good yields of the corresponding aldehyde. An interesting variation of the reaction conditions was found in the treatment of the C- methylpteridines with POBra, which leads to the same mono- and di-bromomethyl derivatives. 6-Methylpterin reacts with more difficulty and with an excess of bromine in hydrobromic acid forms the... 

The a-ionization of 7-methylpteridines can also be utilized in aldol-type condensation reactions. 7-Methyl-pterin and -lumazine and 2,4-diaminopteridine condense readily in aqueous base with aromatic aldehydes to afford 7-alkylidenepteridines (77JOC2951). A Claisen condensation requires the protection of the acidic hydrogens of the amide bonds. 

Hydroxy-7-methylpteridine (neutral species) is hydrated in the 7,8-position, but it is transformed by hot, dilute acid into what appears to be an isomer in which water occupies the 3,4-position the water is liberated by alkali from the latter isomer at a measurable rate to give the anhydrous anion common to both species. ... 

The blocking effect of the methyl group in 4-methylpteridine has been found to decrease the ratio of the hydrated to the anhydrous species in the neutral molecule and in the cation,but the small proportion of hydrated cation rapidly undergoes the ring-opening reaction 19 20 and hence is steadily regenerated from its anhydrous form. 2-Methylpteridine behaves like pteridine, but in 7-methyl-pteridine the action at a distance (+M) effect of the methyl group (see Section III,C,2) produced a smaller ratio of the hydrated to anhydrous species. 

Fig. 1. Serial spectral scans following rapid neutralization of an alkaline solution of 6-hydroxy-2-methylpteridine.

In the case of 2- and 6-hydroxypteridine and their derivatives, the anhydrous species in neutral solutions (produced by rapid addition of equilibrated alkaline solutions to neutral buffers) change sufficiently slowly into the hydrated species that serial scans on a recording spectrophotometer can be used to demonstrate the process. The results shown in Fig. 1 for 6-hydroxy-2-methylpteridine are typical. 

In studies of the hydration and dehydration of pteridine and the methylpteridines, but not levelled out as solutions were made more acid. This was explained by assuming that hydronium ion catalysis of the reactions proceeded only by the formation of the cations of HY+ and HX+, respectively. This effect is strikingly shown by 1,3,8-triazanaphthalene, for which the pH-rate profile of is V-shaped between pH 6.82 and 10.29 but levels out and remains constant from pH 5.3 down to, at least, 2.4. ... 

Dihydroxypteridine was expected to undergo hydration but, a priori, it was difficult to decide whether covalent hydration would occur across the 3,4- or the 7,8-position, or both. Kinetic and spectroscopic evidence now indicate that addition of water occurs much more rapidly across the 3,4-positions (and, hence, that the energy of activation must be less for this site), but the 7,8-water-adduct is thermodynamically the more stable. With time, the concentration of the species hydrated in the 3,4-position reaches a maximum (about 64% of the total concentration). Thereafter, it falls steadily and the concentration of the 7,8-adduct rises until, at equilibrium, the latter accounts for 92% of the total and the 3,4-adduct for only 7.6%. In 2,6-dihydroxy-4-methylpteridine, the methyl group drastically reduces the extent of water addition to the 3,4-position but does not significantly affect 7,8-addition, so that, spectroscopically, only a first-order conversion of anhydrous molecule into the 7,8-water-adduct is observed. ... 

In another study, 4-methylpteridine (6) and 4-trifluoromethyl pteridine (7) showed that substituents can, in some instances, not only change the extent of hydration but also the preferred site of hydration (Figure 5).17 Experimental results indicate that the 4-trifluoromethyl analogue hydrates initially across the 5,6- and 7,8-double bonds to form the dihydrate. Over... 

Chemical methods for folic acid detection are not useful for unfractionated biologic materials (H16). Reduction of folic acid in acid yields a methylpteridine and N-(p-aminobenzoyl) glutamic acid. The latter is estimated by a method for aromatic amines (B33). Another assay method of historical interest is the growth of chicks as a measure of the folic acid content of crude biological mixtures. 

The reaction of 6-methylpteridines with A -chlorosuccinimide has been shown to be a mild and efficient route to 6-trichloromethylpteridines and other similarly substituted heterocycles in yields in excess of 70% avoiding the experimental problems associated with phosphorus-based reagents <2007CL552>. 

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