Purines. V. Reaction of 9-phenyl-9H-purine-6-carbonitrile with nucleophilic reagents.

An Efficient Synthesis of 7,8‐Dihydropyrimido[5,4‐d]pyrimidines

“…In the current work, these reactions were repeated with 9-phenylpurine 1a, and the results are compiled in Scheme 2. The reaction between purine 1a and hydroxylamine did indeed provide the 6-amidinopurine 2d in a comparable yield (71 [23] vs. 76 %), the values reported in the literature for the 1 H NMR chemical shifts of compound 2d [23] being in good agreement with those obtained for the same product in the current work, whilst a careful study using NMR correlation techniques (HMQC and HMBC) also confirmed the structure proposed for this compound. Use of hydrazine hydrate, however, resulted in the 7,8-dihydropyrimido [5,4-d]pyrimidine structure 4a, isolated in 84 % yield (Scheme 2).…”

“…In the reaction between 1a and piperidine, a complex mixture was present after 4 h under reflux conditions. Tlc indicated that the starting material was still present, and the reaction mixture was heated at reflux for a further 17 h. A major compound was clearly present, and this was isolated and identified as the pyrimido [5,4- [23] The formation of compound 6a can be explained if the 6-amidinopurine 2b is initially formed and reacts further to afford 6a through ring-opening at C8, followed by intramolecular cyclization (Scheme 2). The same intermediate species 5 can be generated if ring-opening of the 6-cyanopurine precedes the nucleophilic attack on the cyano group to generate the amidine substituent in the 6-position.…”

“…Three of the reactions reported by Higashino [23] were repeated under the conditions reported in the literature.…”

Efficient conversion of 6-cyanopurines into 6-alkoxyformimidoylpurines

“…1,20-23 Previous reports on the reactions of 6-cyanopurines with amines are confusing in that some authors report nucleophilic attack on the cyano group 24 while others suggest that treatment with methanolic ammonia results in attack at the imidazole ring with rearrangement to give a pyrimido [5,4-d ]pyrimidine in unspecified yield 20-22,25,26 or 17% yield. 23 When this reaction is performed in a pressure vessel at 0-18 ЊC, the reported yield of rearranged product raises to 75%.…”

The Synthesis of 6‐Amidino‐2‐oxopurine Revisited: New Evidence for the Reaction Mechanism

“…[4] Unlike in the cases of adenine and adenine derivatives, which have been extensively studied, only a few reports on the synthesis of purines possessing a strongly basic carboxamidino substituent at the 6-position are available. The formation of these compounds has been claimed to occur through nucleophilic attack by a primary or secondary amine on a 6-cyanopurine, [5] or through addition of ammonium chloride to an imidate intermediate, generated by treatment of a 6-cyanopurine with catalytic amounts of sodium methoxide in methanol. [6] A limited number of publications on the synthesis of 4,4Ј-biimidazoles are available.…”