Uracil-5-carboxylates

The most common synthetic approaches to both types of pyrimidopyrimidine have been described in CHEC-I and in review articles by Delia . In addition some new strategies in the preparation of pyrimido[4,5-rf]pyrimidines have been developed in the last few years. A new approach is the aza-Wittig-type reaction of iminophosphoranes of 5-aminouracils with aromatic isocyanates which leads to functionalized pyrimido[4,5-rf]pyrimidines. Ethyl 1,3-dimethyl-6-(triphenylphosphoranylideneamino)-uracil-5-carboxylate (105) reacts with isocyanates via adduct (106a) intermediates to afford 7-ethoxypyrimido[4,5-. 

A suspension of methyl uracil-5-carboxylate monohydrate (15.04 g, 80 mmol) in HjO (400 mL) was treated with 25% Fj in Nj (1.95 equiv). CaCOj (15.6g) and sodium bisulfite (5.2g) were added to the chilled mixture. Removal of the solvent gave a white solid (23.7 g) which was chromatographed (silica gel, acetone/ CHCl, 1 3) to give the product as colorless needles yield 13.00g (79%) mp 171-172 C. 

Cocrystal products of 4,4 -bipyridine with barbituric acid, orotic acid, and uracil-5-carboxylic acid... 

Compound 205 can be synthesized by (i) the reaction of uracil-5-carboxylic acid 206 with an excess of sulfur tetrafluoride and small amount of water (0.5 mL per 45 g of sulfur tetrafluoride) (Scheme 12.41), (ii) radical trifluoromethylation of 187 using bis(trifluoromethyl)mercury in the presence of azoisobutyronitrile (AIBN) (Scheme 12.41), (in) an electrolysis of a solution 187 in trifluoroacetic acid (Scheme 12.41 ), (iv) the reaction of 5-trifluoromethyl-5,6-dihydrouracil 207 with bromine in acetic acid followed by heating in dimethylformamide (DMF) solution... 

Pyrazolo[4,3-d]-p3uimidine 346 was prepared on refluxing diazido 318 in DMF through 1,5-electrocyclization and functional group migration. Subsequent removal of the ester led to 347 (Scheme 132). Photochemical oxidation of C-4 unsubstituted DHPM analogs, formed uracil-5-carboxyl-ate 348 and 349, respectively (91JCS(P1)1342). 

Photodecomposition of carbohydrate-derived geminal diazides appears to proceed via intermediate carbenes, ° whereas irradiation of the diazidomethylpyrimidine (70) in acetone affords the uracil carboxylate (71), but only in the presence of oxygen. 

The molecular pattern of a bis-complex with orotic (uracil carboxylic) acid (C5H3N204) is also monomeric but with pentagonal coordination around UOf+ from two monodentate carboxylic groups and three water molecules. The U-O bonds are of normal lengths and make normal angles [68]. 

Complementary triple hydrogen-bond formation involving transition metal complexes has been little studied. Mingos et al. [68] have investigated the cocrystallisation of platinum(II) complexes of the uracil derivative orotic acid (2,6-dioxo-l,2,3,6-tetrahydropyrimidine-4-carboxylic acid), which generally coordinates as the dianion, and 2,6-diaminopyridine (2,6-dap), in which complementary A-D-A---D-A-D triple hydrogen bonds are formed between the orotate... 

The most interesting and important member of this series is orotic acid or uracil 6-carboxylic acid, (I). This compound was synthesized in 1897 by the condensa-... 

Uracil-6-acetic acid [242] (XXVll), wherein the carboxylic acid group is attached to the pyrimidine ring through a -CH2- linkage, was found to inhibit the germination of conidia of Peronospora tabacim in vitro [243]. 

A common intermediate for all the nucleotides is 5-phosphoribosyl-l-diphosphate (PRPP), produced by successive ATP-dependent phosphorylations of ribose. This has an a-diphosphate leaving group that can be displaced in Sn2 reactions. Similar Sn2 reactions have been seen in glycoside synthesis (see Section 12.4) and biosynthesis (see Box 12.4), and for the synthesis of aminosugars (see Section 12.9). For pyrimidine nucleotide biosynthesis, the nucleophile is the 1-nitrogen of uracil-6-carboxylic acid, usually called orotic acid. The product is the nucleotide orotidylic acid, which is subsequently decarboxylated to the now recognizable uridylic acid (UMP). 

Alkylation of pyridazinone 945 with 4-bromoacetoacelic acid 944 did not give the 2 -oxo-4 -carboxylic acid analogs, but gave 946 of type 4.1. The uracil derivatives were prepared similarly (90MI4). 

Two traditional methods have been used to Introduce a carboxyl substituent at C-5 of uracil. 0ns iasolves bromlnatlon at C-5, metalatlon via a lithium-halogen exchange, and finally quenching with carbon dioxide (32) to give the C-5 carboxylic acid. The... 

Orotic acid (uraciI-6-carboxylic acid), an intermediate in the biosynthesis of uracil, also reacts smoothly with CF3SCI in pyridine to give the 5-substituted compound. The pyridinium salt initially formed can be easily cleaved with dilute hydrochloric acid ... 

Diazouracil and derivs 5 D1180—D1181 5 -diazouracil-4-carboxylic acid 5 D1181 5-diazouracil ethyl ether 5 D1181 5-diazo-4-isonitrosomethyl-uracil 5 D1180... 

Hydroxypyridine undergoes the Kolbe reaction (with carbon dioxide to give the carboxylic acid) the Na salt reacts mainly at the 2-, and the K salt at the 6-position. Uracil undergoes the Reimer-Tiemann reaction with sodium hydroxide/chloroform to give 5-formyluracil. 

Photochemical reactions of the purines and pyrimidines assume special significance because of the high molar extinction coefficients of the nucleic acids present in cells. Light is likely to be absorbed by nucleic acids and to induce photoreactions that lead to mutations.190 Both pyrimidines and purines undergo photochemical alterations, but purines are only about one-tenth as sensitive as pyrimidines. Photohydration of cytidine (Eq. 23-25) is observed readily. The reaction is the photochemical analog of the hydration of a,P-unsaturated carboxylic acids. Uracil derivatives also undergo photohydration. 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under reflux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl Uracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give N-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

A number of cyclic imides, such as uracil (11), can be used in conjunction with a nitrogenous base.64 These compounds are added to hydroxylamine developer formulations. Several thioether-substituted 2,4- or 4,6-dihydroxypyrimidines, such as (12), are useful.65 Thioether-con-taining carboxylic acids can be used in the preparation of electrically conducting transferred silver images. These include 3-thiapentanoic acid, 3-thiapentanedioic acid and 3,6-dithiaoctanedioic acid.66 Mercaptobenzoic acids are used alone or with a cyclic imide solvent to produce lithographic... 

Fujita S, Steenken S (1981) Pattern ofOFI radical addition to uracil and methyl-and carboxyl-substituted uracils. Electron transfer ofOFI adducts with N,N, Ar, Ar -tetramethyl-p-phenylenediamine and tetranitromethane. J Am Chem Soc 103 2540-2545 Fujita S, Nagata Y, Dohmaru T (1988) Radicals produced by the reactions of SO4 with uridine and its derivatives. Studies by pulse radiolysis and y-radiolysis. Int J Radiat Biol 54 417-427 Fujita S, Horii FI,Taniguchi R, Lakshmi S, Renganathan R (1996) Pulse radiolytic investigations on the reaction of the 6-yl radicals of the uracils with Cu(ll)-amino acid complexes. Radiat Phys Chem 48 643-649... 

Orotic acid (uracil-6-carboxylic acid), first isolated147 from milk, has been amply demonstrated to be an effective precursor of nucleic acid and nu-... 

When treated with sodium metaperiodate, the barium salt of orotidine consumes one mole of oxidant per mole without the liberation of formic acid, in accord with a pentofuranosyl structure.119 The structure of orotidine, therefore, is certainly l-(D-ribofuranosyl)uracil-6-carboxylic acid (XXXII). 

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