Heterocyclic synthesis uracils

Wamhoff, H., Dzenis, J., Hirota, K., Uracils Versatile Starting Materials in Heterocyclic Synthesis, 55, 129. 

A lot of information about the structure, reactivity, and the best synthetic approaches for pyrimidopyrimidines has been described in CHEC-I. Additionally, some new methods of preparation of pyrimidopyrimidines have been reported in reviews on the synthesis of fused pyrimidines by Delia and Warner starting material in heterocyclic synthesis by Wamhoff, Dzenis, and Hirota <92AHC(55)129>. Pyrimidopyrimidines are especially interesting as structural analogues of natural compounds. 

Uracils Versatile Starting Materials in Heterocyclic Synthesis. 55, 129. 

Heinrich Wamhoff and Jorg Dzenis discuss the synthesis, structure, and reactions of uracils with particular emphasis on their utility in heterocyclic synthesis. 

It was shown that other nucleophiles can undergo analogous reactions with 5-trifluoromethyluradl or its derivatives, e.g. amines (methoxyamine [749]), bisulfite [750], and NH4OH (to form 5-cyano-2 -deoxyuridine) [751]. Recently, this reaction was used for the synthesis of various heterocycles containing uracil moiety 1216-1219 (Scheme 264) [752],... 

Aryl and heteroaryl nitrene insertion processes have also been employed in the synthesis of heterocycles. The azide 459, for example, is converted on irradiation into the imidazole 460,383 and dihydro-10-thiaisoalloxazines are obtained in good yield on photoelimination of nitrogen from 6-(2-azido-phenylthio)uracils.384... 

Pyrimidine annulated heterocycles fused at positions 5 and 6 to uracil were synthesized via a three-step sequence starting from uracil 63 [20]. Firstly, the reaction with 3-bromocyclohexene gave the AT-allyl-vinyl core system 64 in 80% yield. Upon heating 64 in EtOH in the presence of HCl, aza-Claisen rearrangement gave rise to the C-cyclohexenyl uracil 65 in 38% yield. Final bromination ( 66) and dehydrogenation steps ( 67) allowed synthesis of the desired tricyclic fused uracil systems (Scheme 15). 

A general transformation important for the synthesis of polycyclic heterocycles is the Smiles rearrangement of azaheterocycles. In the case of uracils, 6-chloro-5-nitro derivatives react with o-aminothiophenols. By such S - N rearrangements (710R99 73MI1), pyrimido[5,4-6][l,4]ben-zothiazines besides pyrimido[4,3-/>]benzothiazolines are formed (74CPB1265 80T2097) (Scheme 116). 

This brief review on uracil and its chemistry, by no means exhaustive, has pointed out by some selective but typical examples that show uracils and their derivatives possess considerable synthetic potential. In most cases, a few easy reaction steps enable the synthesis of novel and highly interesting types of condensed heterocycles which are difficult to obtain by other synthetic means. 

Kutterer, K.M.K., and Just, G.. Cyano/diallylamine additions to glycoside and nucleoside aldehydes and its application to the synthesis of polyoxin L and uracil polyoxin C, Heterocycles, 51. 1409, 1999. 

---