6- Azauracil amino derivatives

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

Cytidine has been converted into l-(5-amino-5-deoxy-j8-D-arabinofuranosyl) cytosine by a sequence of reactions involving A-benzoylation, sulphonation, acetylation, displacement with azide ion, e/c., and l-(3-amino-3-deoxy-jS-D-arabinofuranosyl)-6-azauracil was derived from 2, 3 -di-0-methanesulphonyl-5 -O-trityl-6-azauridine via 2,2 - and 2, 3 -anhydro-nucleosides. Other syntheses have been accomplished by the condensation of an appropriately derivatized amino-sugar with either a pyrimidine or purine derivative for example, the Hilbert route was used to prepare l-(2-amino-2-deoxy-a-D-arabino- and -jS-o-xylo-furanosyl)cytosine. > The reactivity of l,3,4,6-tetra-0-acetyl-2-acyl-amido-2-deoxy-j3-D-glucopyranoses in condensation reactions with 2,6-dichloro-purine, theophylline, and 6-benzylaminopurine was shown to be in the order benzamido > acetamido > phthalimido. 9-(3-Acetamido-2,5-di-0-acetyl-3-deoxy-j8-D-ribofuranosyl)-2,6-dichloropurine has been synthesized and converted into the corresponding 2,6-diamino- and 6-amino-2-chloro(fluoro)-nucleosides. ... 

The structures of 5-azacytosine and related compounds are of interest because of their biological importance (see Section 2.20.5.6). l-Methyl-5-azacytosine exists in the amino-oxo form (23). 5-Azauracil (l,3,5-triazine-2,4-dione) is of particular interest. IR spectra indicate that it exists in the dioxo form in the solid, but H NMR studies have been interpreted to show that it exists in the monoenolic form in solution. The spectra showed a non-exchange-able sharp singlet at 8.18 8 (H, 24) (760MR(8)224). Derivatives of 5-azacytosine and 5-azauracil are covalently hydrated. Thus 5-azauridine exists entirely in the crystal form as (25) (76MI22000, p.l39>. 

Novel mesoionic structures 22 have been obtained via the internal cyclization of thio- and amino-acid derivatives of 6-azauracil 21. These compounds undergo ring-opening reactions with amines to yield the respective 6-azauracil amides 23. <05TL5325>. 

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