2- pyrimidine, effect heating

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

A hydrazine or substituted hydrazine in lieu of the amino group on the pyrimidine precursor is also an effective species. In what may be described as a Fischer indole-type reaction, 2-amino-6-hydrazino-4(3//)-oxopyrimidine 129 undergoes thermolytic cyclization when heated with compounds 130 (Scheme 12). The resultant product 131 is obtained in modest yield <1996H(43)323, B-2002MI439>. 

A synthesis of the monoterpene alkaloid ( )-actinidine has been accomplished through the intramolecular cycloaddition of a substituted pyrimidine (81JCS(P1)1909). Condensation of the diester (756) with formamidine provided the pyrimidine precursor (757) which when heated at its melting point (203 °C) underwent cycloaddition with elimination of isocyanic acid to produce the pyridone (758). Conversion of the pyridone into the chloropyridine was effected with phosphoryl chloride. The chlorine atom was then removed by hydrogenoly-sis over palladium on charcoal to afford the racemic alkaloid (759 Scheme 175). 

The most important route is the conversion of pyrimidines into 1,3,5-triazines. The first one-step transformation was effected by Taylor and Jefford (62JA3744) by heating the pyrimidine (179) with benzenesulfonyl chloride in pyridine (equation 106). The reaction may be considered as an example of an abnormal Beckmann rearrangement. The mechanism of the reaction of the 4-aminopyrimidine (180) is probably dependent on the nature of the 2-substituent (180, R). If R is an electron-releasing moiety, pathway B seems more likely (Scheme 109). The 4-hydroxypyrimidine (179 R = OH) behaves similarly. Many 2-cyano-1,3,5-triazines may be synthesized by this method. 

An alternative solution to the workup issue relied on the attachment of CH-acidic compounds 64 to a soluble polymer support (PEG-4000). The approach improved the yields of the dihydropyrimidinones 66 by the use of a 2-fold excess of other components—urea and aldehyde in the microwave-assisted solvent-free cyclocondensation [118]. Another single-step approach towards 4,5-disubstituted pyrimidines was based on cyclocondensation of a variety of aromatic, heterocyclic and aliphatic ketones, formamide and HMDS as the ammonium source [119]. The high temperature (215 °C) required to effect the formation of pyrimidines was secured by microwave dielectric heating in sealed vessels (Scheme 45). 

BSA was effective for the derivatization of purine and pyrimidine bases [456] and nucleosides [457]. Bases were silylated by heating at 150°C with BSA—acetonitrile (1 3) for 45 min. It was stated that under these conditions the TMS derivative of guanine can be prepared reproducibly, but both cytosine and 5-methylcytosine provided two peaks. Silylation of nucleosides, including pseudouridine, was carried out by heating at 120°C with a 100-fold excess of BSA for 2 h. With the use of OV-17 as the stationary phase, this procedure was adopted for the determination of the composition of ribonucleic acids. 

In most cases convergent types of syntheses are the most cost effective and preferred for various reasons. However, that was not the case with ERH-1 as it will show in the following examples. In the convergent approach (see Scheme 3) it was assumed that barbituric acid would be a cheap source ( 4 per kg) for the pyrimidine portion since it was prepared from inexpensive materials such as ethyl malonate and urea with sodium ethoxide as a condensing agent. Numerous reports [4] have shown that barbituric acid is easily converted to 2,4,6-trichloropyrimidine by heating with phosphorus oxychloride and a trialkylamine. Our intent was to couple 2,4,6-trichloropyrimidine 10 to 2,2-dimethyl-1-indanone followed by various reactions that would lead to ERH-1 [5] as shown in Scheme 3. 

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