Uracils 5-cyano

The preferential reaction of uracil with HCN in aqueous solution3,7 (but not with Br", I", or SCN" 64) appears to go through a sequence140 uracil - A - B - other products, in which A is probably 5-cyano-5,6-dihydrouracil, and B is 5-cyanouracil. There were two final (unidentified) products. The reaction step A -> B is inhibited by oxygen. 

Indirect evidence for the formation of anionic adducts has been obtained for some dehalogenation reactions of 5-haIouracils or 5-halo-5,6-dihydro-uracils with bisulfite ion in water.163"165 However, no adducts were detected in the course of these reactions. Similarly, the formation of adduct 120 was assumed in the reaction of 6-bromomethyl-l,3-dimethyl-5-nitrouracil with KCN to yield 6-cyano-l,3-dimethyl-5-nitrocyclothymine.166 Clearly, in all these reactions involving the uracil system, the ring charge delocalization is quite limited, and the resulting stability of the adducts is markedly reduced. 

However, this reaction requires relatively high concentrations of cyanate (> 0.1 M), unlikely to occur in aqueous media given its rapid degradation to carbon dioxide and ammonia. In order to optimize the yield of cytosine by this procedure, cyano acetylene 15 was treated with a lower amount of cyanate at 100 °C. Under these more efficient experimental conditions cytosine was obtained in 19% overall yield along with a low amount of uracil [79]. An alternative route explored consists of the use of urea 19, which is considered a common prebiotic precursor [80], as one-carbon atom donor in the place of cyanate. The reaction of cyano acetylene 15 (1.0 M) with 19 (1.0 M) at 100 °C gave cytosine 17 in 5% yield (Scheme 11). At low concentrations of 19 (< 0.1 M) this reaction does not produce detectable amounts of cytosine [81]. 

The creation of a thiophene ring from 0/7/w-cyano-methylpyrimidines has provided access to thieno[3,4-c/]pyrimidines. Mono- or di-iV-(substituted)uracils (278) undergo reaction with elemental... 

The lactim ether (59) derived from 3-carbethoxycaprolactam condensed with urea to give a fused uracil in low yield, but the analogous reaction with the cyano derivative (60) failed. 

The reaction of 1,3-disubstitued uracils possessing an electron-withdrawing group, such as nitro, carbamoyl, and cyano at the 5-position with primary amines, results in the exchange of the N-l portion of the uracil... 

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. 

Reaction of 5-cyano-3-methyl-l-phenyluracil (146) with amines induced rearrangement, instead of an N1 exchange reaction, to give 6-amino-3-methyl-l-phenyl-5-(N-substituted iminomethyl)uracil (147) (89CPB2008) (Scheme 45). 

A practical synthesis of 2//-pyrimido[4,5-e]ll,2,4]triazin-3-ylidenecyanamides 106 has been developed. The key step is the coupling reaction of an aryldiazonium salt with l-cyano-3-(2,6-dioxo-l,2,3,6-tetrahydropyrimidin-4-ylamino)-2-methylisothiourea 105, obtained from uracil 104, followed by an intramolecular cyclization <04TL931ft>. 

C-cyano-3 -deoxy-P-D-ffcr o and erythro nucleosides 47 (63%) and 31 (25%). Related openings of 2, 3 -anhydro-P-D-lyxofuranosyl nucleosides with sodium cyanide [84] and with diethylaluminium cyanide [85] to afford 3 -C-cyano-3 -deoxy-P-D-arabinofuranosyl derivatives of adenine, uracil, thymine and isocytosine have been described. 

Uldry etal. on uracil and 4-cyano-4 -ethynylbiphenyl, andMafraetal. on ciprofloxacin polymorphs, GIPAW CST and NICS calculations on the piece-wise deconstructed crystalline lattice are used to deconvolute these effects [20, 59]. 

Walczak introduced chiral substituents onto the nitrogen of uracils (64) via reaction with amino acid derivatives (65). This mild method did not lead to epimerization of the chiral center and offered an alternative to alkylation of the uracil nitrogen. An electron-withdrawing group (nitro or cyano) on the uracil ring was necessary for product (66) formation. 

Walczak and co-workers employed an acid-catalyzed Dimroth rearrangement in their novel transformation of 5-cyanouracil derivatives. Treatment of 5-cyano uracil 150 with l-amino-2-hydroxypropanone in anhydrous ethanol at room temperature gave the corresponding Dimroth product 151 in 51% yield. 

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