Pyrimidine glycols

However, if non-tertiary, oxyl radicals in aqueous solution are capable of undergoing a rapid 1,2-H-shift [44-46] [reaction (34)] in competition with fragmentation. Then after addition of oxygen, superoxide is eliminated [reaction (36)]. Thus under these conditions also, superoxide radicals are likely intermediates which are expected to react with peroxyl radiceds, reducing them to the corresponding hydroperoxides. These are abundant, though somewhat unstable, products in the radiolysis of air-saturated pyrimidine solutions. They are considered to be important precursors of the pyrimidine glycols observed under various conditions [1]. 

In a somewhat related reaction the fused lactone (142) furnishes the decahydropyrido[3,4- f]pyrimidine (143) during the reaction of a-(hydantoin-5-ylidene)-7-butyrolactone with ammonia in ethylene glycol at 200 °C (71KGS1280). 

Pyrimidines have also served as electrophiles in crown synthesis from this group. 4,6-Dichloropyrimidine reacts with diethylene glycol and sodium hydride in anhydrous xylene solution to form the 20-crown-6 derivative as well as the other products shown in Eq. (3.48). Note that a closely related displacement on sy/rr-trichlorotriazine has been reported by Montanari in the formation of polypode molecules (see Eq. 7.5). 

Of greater versatility is an extension of Albert and Royer s acridine synthesis. The first successful use of this in the quinazoline series was for the removal of the chlorine atom in 2-chloro-4-phenylquin-azoline, although it had been used previously to prepare 8-nitro-6-methoxyquinazoline in very poor yield. The 4-chloroquinazoline is converted to its 4-(A -toluene-p-sulfonylhydrazino) quinazoline hydrochloride derivative which is decomposed with alkali in aqueous ethylene glycol at lOO C (Scheme 13). The yields are high (60-70%) when R is Me, Cl, OMe but low when R is NO2, and in the latter case it is preferable to use dilute sodium carbonate as the base. This reaction is unsatisfactory if the unsubstituted pyrimidine ring is unstable towards alkali, as in 1,3,8-triazanaphthalene where the pyrimi-... 

Cyclization of A -aryl-2-(ethoxycarbonyl)-3-(2-pyridylamino)acrylamides 307 in AcOH, and in PPA, or in ethylene glycol afforded A-aryl-4-oxo-4//-pyrido[l,2-n]pyrimidine-3-carboxylic amide 308 (94KGS629, 95KFZ(5)39). 

There is always interest in the photochemistry of the pyrimidine nucleic acid bases and related simple pyrimidinones, due to its importance in genetic mutation. In addition to damaging DNA, photo-induced reactions may also repair the damage, as in the reduction, by FADH, of the thymine glycol 64 back to thymine <06JACS10934>. Another report related to repair of DNA involved a model study, by means of the linked dimer 65, of the involvement of tryptophan in the electron-transfer leading to reversion of thymine oxetane adducts <06OBC291>. 

A typical proposed reaction mechanism is shown in Chart 9. The ultimate stable products are 5,6-glycols of the pyrimidine, 5- or 6-hydroxyprimidines, and degradation products. The primary products in the case of purines are degradation products formed perhaps through transient peroxidization at the bond joining the two rings, the central 4,5 bond. 

Irradiation of air-free solutions of pyrimidines can give products resembling some of those produced by ultraviolet light, but probably by a quite different mechanism. Irradiation of 1,3-dimethyluracil with 200 kV X-rays produces not only the expected 5,6-glycol, but also 6-hydroxyl-l,3-dimethyl-5-hydrouracil, the same isomer as the UV-produced hydrate discussed elsewhere in this chapter. The yield of the hydroxy compound is low, G = 0.35 molecules/100 eV absorbed. Cytosine glycol is formed in gamma-irradiated cytosine solutions, and this deaminates completely to the uracil glycol. These products are probably formed by addition of an OH to the 6-position of the pyrimidine and then dismutation of hydroxy radical. The major products formed in the radiolysis of air-free solutions of pyrimidines or purines have not yet been identified. 

Fusion of 2-methylpyrido[2,3- [l>3]oxazin -one 555 with ammonium acetate, hydrazine hydrate, benzylamine, and aniline in the presence of anhydrous zinc chloride at 150-160 °C gave the pyrido[2,3-. Also, amination of the 2-isopropyl or isobutyl analogues of 555 (R = = H) with benzylamine in ethylene glycol... 

The cyclization of 3-[2-[4-[(2-fluorophenyl)-(2-phenylhydrazono) methyl]-l-piperazinyl]ethyl]-2-methyl-4/7-pyrido[l,2-a]pyrimidin-4-one 452 in boiling ethylene glycol in the presence of potassium carbonate overnight gave indazole derivative 453 in 25% yield (90EUP353821, 90USP4957916). Ocaperidone 8 was obtained when the Z oxime 454 was stirred in toluene in the presence of aqueous potassium hydroxide at 45-55°C for 0.5 hour, then at reflux for 3 hours (91EUP453042). 

A solution of 0.11 g of sodium in 3.0 ml of ethylene glycol and equivalent of 4-t-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl]benzenesulphonamide were heated to 100°C, cooled for a further 4 hours, poured on to ice and adjusted to pH 3 with 1 M tartaric acid. The suspension obtained was extracted with ethyl acetate, the organic extracts were combined, washed with water, dried with sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on silica gel with CH2CI2-ethyl acetate 9 1 and yielded 4-t-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl]benzenesulphonamide as a solid. Sodium salt melted at 195°-198°C. 

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