Pyrimidine derivatives and related compounds. Part 50. Photochemical reaction of 5-substituted 6-azido-1,3-dimethyluracils with nucleophiles. Ring transformation of pyrimidine to 1,3,5-triazepine and hydantoin ring systems

Abstract

Photolysis of 5-substituted 6-azidouracil derivatives in the presence of nucleophiles has been studied.Irradiation of 5-alkyl-6-azidouracils (3) in the presence of amines caused a ring expansion to give 1,3,5triazepine derivatives (7). Photolysis of 6-azido-1,3,5-trimethyIuracil (3a) in alcohols gave the corresponding 6,6-dialkoxy-5-amino-5,6-dihydrouracils (8). When compound (3a) was irradiated in water, a ring contraction occurred to afford 3,5-dimethylhydantoin (9). On the other hand, 6-azido-5cyano-l,3-dimethyluracil (4) was converted into 1,3,5-triazepines (13) only in the presence of alcohols.Several studies on the chemistry of azido compounds have been carried out because of their interesting reactivity and utility in organic synthesis as reagents or intermediate^.^ Aryl azides display a variety of thermochemical and photochemical reactivitie~.~ For example, it has long been known that photolysis of phenyl azides in the presence of amines produces a ring expansion to give azepine~.~ Much effort has recently been expended in elucidating the reaction mechanism6 of this conversion and in applying it to other aromatic azides.' On the other hand, although the isomerization between the azido group and the tetrazole ring for aromatic heterocyclic azides has been extensively investigated,8 their ring expansion to sevenmembered heterocycles has received less attention apart from a few example^.^^'^ We recently reported that the photolysis of 6-azido-1,3dimethyluracil (1) with amines and acyl chlorides led to the formation of 6-alkylamino-5-amino-1,3-dimethyluracils (2; X = NRR'. Y = H) l o and 5-acylamino-6-chloro-1,3-dimethyluracils (2; X = C1, Y = COR)," respectively, oiu an aziridine intermediate (A) (Scheme 1). In connection with these studies, it was clearly of interest to examine the photochemical reaction of 5-substituted 6-azidouracils with nucleophiles because of the predicted difficulty of converting the intermediate, corresponding to (A), into the 5-aminouracil(2).In this investigation 5-alkyl-6-azido-1,3-dimethyluracils (3a and b), 6-azido-5-cyano-1,3-dimethyluracil (4), and 6-azido-5benzyl-3-methyluracil (5) were used as the 5-substituted derivatives. It was found that the photolysis of these compounds takes a quite different path from that of 5unsubstituted uracils l o and causes a ring transformation to give a 1,3,5-triazepine or hydantoin ring system. Results and Discussion5-Substituted 6-azidouracils (3)-(5), employed here as starting materials, were prepared by treating the corresponding 6-chlorouracils 12,' with sodium azide. Me h e (3a) ( 3 b ) I Me I HFirst, photolysis of 6-azido-1,3,5-trimethyluracil (3a) was carried out in the absence of any nucleophile. When a solution of (3a) in tetrahydrofuran (THF) was irradiated, a reduction product, 6-amino-1,3,5-trimethyluracil (6),12 was formed.On the other hand, irradiation of the azidouracil (3a) in the presence of methylamine in THF gave a ring-expansion product, 1,3,6-trimethyl-4-methylamino-2,3,6,7-tetrahydro-lH-1,3,5-triazepine-2,7-dione (7a), i...

Advances in 1,3,5-triazepines chemistry

“…1,3,5-Triazepine-2,7-diones 19 were obtained from the irradiation of 5-cyano-6-azidouracil 18 in an appropriate alcohol, i.e., methanol, ethanol, or propan-2-ol. 84 Deprotonation/alkylation reactions of triazepinedione 20 produced either mono-or dialkylated products depending on the reactant ratio, solvent, and the nature of the electrophile as well as the base (Scheme 1). 85 The irradiation of azido-substituted pyrazines 21 and pyrimidines 23 bearing strong electron-donating substituents in the presence of MeONa or diethylamine gave 1,3,5-triazepines 22 and 24 via a ring expansion (Scheme 2).…”

“…66 A similar transformation was observed on irradiation of a series of 6-azidouracils in the presence of a primary or a secondary amine. 84 The low-temperature photooxygenation of 7,8-dihydro-8-oxoguanosine gave 3-substituted 1,3,5-triazepane-2,4,6,7tetraone as the second major product. 86 The thermolysis of 5phenyltetrazolo[1,5-c]quinazoline provided the polycyclic dimer 7 (Fig.…”

Leveraging the Domino Skeletal Expansion of Thia-/Selenazolidinones via Nitrogen-Atom Transfer in Hexafluoroisopropanol: Room Temperature Access to Six-Membered S/Se,N-Heterocycles

“…Beside such peripheral functionalization, development of methods pertaining to single atom editing of the underlying molecular skeleton of heterocycles has received growing attention. − However, compared to venerable carbonyl-centered ring-expansion reactions such as Beckmann, Baeyer–Villiger, and Schmidt reaction, skeletally focused ring-expansion/editing strategies of heterocycle are still sporadic. Among the known examples of inter and intramolecular heterocyclic ring-expansion with in cooperation of B-, , C-, − Si-, and N-atom, ,, some selected schemes are shown in Scheme a–f. Yorimitsu reported Ni-catalyzed boron insertion into the C–O bond of benzofuran leading to oxaborins .…”

Unraveling the Photochemistry of the 5-Azido-2′-deoxyuridine Photoaffinity Label

“…Nucleophilic addition of water at position C5 of 6 gives rise to the aziridine intermediate 7 , which undergoes water induced nucleophilic ring-opening at the C5 position to provide the unstable 5,5-dihydroxy-6-aminodihydrouracil 8 . This cascade of reaction is supported by the similar photoreactivity in H 2 O of a 6-azidouracil derivative and the chemical reactivity of its photoproduct . Namely, it has been proposed that photoexcitation of an aqueous solution of 6-azido-1,3,5-trimethyluracil gives rise to the corresponding azirene that is hydrolyzed to the unstable 5-amino-6,6-dihydroxy-1,3,5-trimethydihydrouracil.…”