8‐Arylpurines and their ultraviolet absorption spectra

Abstract

Dehydrocyclization of 4-amino-5-arylamidopyrimidines in polyphosphoric acid to 8arylpurines was further investigated. Various other 8-arylpurines were synthesized by this new procedure in high purity and yield. The ultraviolet absorption spectra of the arylpurines and the corresponding acylamidopyrimidines were measured a t P H 1, 7, and 13 a t 0 . 1 molar ionic strength. The spectra of the purines resemble those of the corresponding acylamidopyrimidines and, to a lesser extent, the corresponding 4,5diaminopyrimidines. The bathochromic shifts caused by different substituting groups in monosubstituted purines, in general, parallel the inductive effect of the substituting groups. The hyperchromicity and the inductive constant of the substituting groups assume a linear relationship, for substitution at either the 2 o r 6 position. These changes in the wave length of maximum absorption and in the molar extinction coefficient caused by 2, 6 and 8 substitutions of the purines reported here a r e in agreement with previous studies by Mason.Recently the dehydrocyclization of 4 -amino -5acylamidopyrimidines to purines with polyphosphoric acid was reported (2). The polyphosphoric acid procedure was found to be superior to other processes (3ag) employed, which generally yield products difficult to purify. The versatility of this new procedure was demonstrated by the preparation of other 8-arylpurines in high purity and yield thereby confirming the previous observation that substitutions 011 the 2 and 6 positions of the pyrimidine ring and on the para position of the phenyl ring had little or no influence on cyclization (2).The quantitative ultraviolet absorption spectra of the pyrimidines and purines synthesized were measured at PH 1, 7, and 13 at 0 . 1 molar ionic strength.Acylation of 4,5-diaminopyrimidines gave &amino-5acylamidopyrimidines ( 2 , 4a-c) ( Table 1) which were purified and analyzed, and appeared a s single spots on paper chromatograms. Cyclization of these acylpyrimidines to 8-arylpurines was performed in polyphorphoric acid at 160-170" (5) a s previously described (2). One recrystallization suffices to give pure compounds which appear a s single spots on paper chromatograms (Table 11).A s the corresponding 4,5-diaminopyrimidines were not available, two substituted purines were prepared by other methods in order to study spectral shifts. Thiation of 2-methyl-6-hydroxy-8-phenylpurine (XX) with phosphorus pentasulfide gave 2-methyl-6-mercapto-8-phenylpurine (XVIII), which was dethiated with nickel catalyst to .%methyl-8-phenylpurine (XIX).The spectra of the arylamidopyrimidines (Table 111) , and of the corresponding 4,5-diaminopyrimidines (6a-e) showed close resemblance except that benzoyl substitution on the 5-amino group caused a hypsochromic shift. Consequently, two narrow bands a r e observed around the regions of 235 and 265 mp. Concerning the molecular extinction coefficient, the absorption in alkaline medium usually is lower than that in the neutral and acidic media. A marked bathochromic effect rel...

Conformationally Restricted Analogues of Trimethoprim: 2,6-Diamino-8-substituted Purines as Potential Dihydrofolate Reductase Inhibitors from Pneumocystis carinii and Toxoplasma gondii

“…A search of the literature revealed that a variety of methods exist for the synthesis of 8-substituted purines . Among the most widely used method is the reaction of an appropriately substituted benzoic acid and a 5,6-diaminopyrimidine followed by acid-catalyzed ring closure . This methodology requires two steps for the assembly of the purine ring, involving initial formation of the 4-amino-5-(acylamino)pyrimidine, followed by ring closure.…”

“…34 Among the most widely used method is the reaction of an appropriately substituted benzoic acid and a 5,6-diaminopyrimidine followed by acid-catalyzed ring closure. 35 This methodology requires two steps for the assembly of the purine ring, involving initial formation of the 4-amino-5-(acylamino)pyrimidine, followed by ring closure. The synthetic scheme utilized in this study for the synthesis of 8-substituted purine analogues is outlined in Scheme 1 and is a modification of the Traube synthesis 36 between a 4,5-diaminopyrimidine and a substituted benzaldehyde.…”