Adenine 1-oxide

Similar transformations have been reported for quinoline 1-oxide and 3-, 4-, 5-, 6-, 7-, and 8-methylquinoline 1-oxides in aqueous solution,151 for quinoxaline 1-oxide,152 for adenine 1-oxide,153 and for phenanthridine 5-oxide (181 R = H) which yields phenanthridone (182 R = H).154... 

Methylation of adenine 1-oxide produces the 9-methyl 1-oxide (157) via an intermediate O-methyl derivative (Scheme 24) <71CPB161l). 

Alkylation of many iV-oxides affords corresponding iV-alkoxypurines although xanthine 1-oxide produced the 1-hydroxybetaine, and the 3-oxide behaves in a similar manner. Alkylation often proceeds better in the presence of hydrogen peroxide (74CPB2466) as in the conversion of adenine 1-oxide into l-methoxy-9-methyladenine with methyl iodide. Similarly alkylation of adenosine 1-oxide and its 2, 3 -0-isopropylidene derivative Afforded the corresponding 1-alkoxy nucleosides <73CPB1676). 

Acylation of iV-oxides usually produces a reactive AC,0-acyl derivative. Adenine 1-oxide, however, with acetic anhydride undergoes ring opening to afford an oxadiazole (Scheme 37) (B-72MI40901, p. 550). 

Adenine 1-oxide Adenine + isoguanine UV light 64B880... 

Adenine 1-oxide 1 -Methoxy-9-methyladenine Mel/HzOz 73CPB1676... 

Examples of all the four purine iV-oxides are known. Purine 1-oxide may be prepared from purine and perbenzoic acid over two weeks (62JOC567), and adenine 1-oxide is similarly prepared from adenine over 2 days (58JA2759). On the other hand hypoxanthine 1-oxide is best obtained by deamination of adenine 1-oxide (66JOC966). Reaction of 5-amino-4-hydroxyformamidinoimidazole with carbon disulfide may be used to make 2-thioadenine 1-oxide which with alkaline peroxide provides a useful route to isoguanine 1-oxide (67JOC1151). 

Purines react slowly with peracids, such as perbenzoic acid (within a week), to yield the 1-oxide. An early report of the synthesis of a purine A -oxide by direct oxidation was the preparation of adenine 1-oxide (1) from the treatment of adenine with acetic acid/hydrogen peroxide. Related purine 1-oxides can be obtained from adenine 1-oxide by deamination. As most purine 7- and 9-oxides are not accessible by direct oxidation, the cyclization of the corresponding pyrimidine or imidazole precursors was undertaken. A review on heterocyclic A-oxides has appeared. ... 

In addition to these reactions, rearrangements occur upon UV irradiation. For example, adenine 1-oxide gives as major products adenine and isoguaninewhereas 6-sulfanylpurine 3-oxide gives 6-sulfanylpurine and a trace of 6-thioxanthine. ... 

A comparison was made of the displacement reaction occurring on 2-(mcthylsulfinyl)-adeninc and its 1-oxide. 2-(Mclhylsulfinyl)adenine 1-oxide was readily converted to isoguanine 1-oxidc (10) in 4% aqueous sodium hydroxide (rt) while 2-(methyIsulfinyI)adcnine remained unchanged in this strength of alkali even at 90 C. ... 

A similar difference is observed upon hydrolysis with 2 M hydrochloric acid. Again, 2-(melhyl-sulfinyl)adenine 1-oxide leads to a good yield of isoguanine 1-oxide, but starting material is recovered from the parent base. -" ... 

A mixture of adenine 1-oxide monohydrate, methyl iodide, aq. 30%-H2O2, and N,N-dimethylacetamide stirred 89 hrs. at room temp. l-methoxy-9-methyl-adenine hydriodide. Y 82%. F. e. s. T. Fujii, S. Kawakatsu, and T. Itaya, Chem. Pharm. Bull. 22, 2466 (1974). 

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