Carbonylation reaction pyrimidines

Formation of Pyrimidines from beta-Dicarbonyl and 1,1-Diamino Compounds. Yet another application of the amine-carbonyl reaction is viewed in the constmction of the pyrimidine ring. Here a 1,1-diamino compound reacts with a beta-dicarbonyl compound, as is outlined in Scheme 4.12. 

With unsymmetrical diketones the orientation of the reaction is again controlled by the reaction of the most reactive carbonyl group with the 5-position of the pyrimidine ring. Thus, benzoyl acetone and 6-aminouraoil gave 5-methyd-7-phenylpyrido[2,3-d]pyrimidine-2,4-(lH,3iI)-dione (71), in preference to the 5-phenyl isomer (72). ... 

Rhodium-catalyzed reaction of iV-butenyl-l,3-propanediamines 538 with a mixture of H2 and CO gave a mixture of hydroformylated 539, 540, and carbonylated products 541, 542 in the presence of a phosphine (PPI13, PBU3, P(C6Hn)3, PO-toDj) (Equation 91) <1997T 17449, 1997TL4315>. When the hindered biphosphite, BIPEPHOS, and a 9 1 or 1 1 mixture of H2 and CO were used, only perhydropyrido[l,2- ]pyrimidine 539 (R = H) was formed from 538 (R = H). 

The Diels-Alder cycloaddition potential of fused 4-aryldihydropyrimidine mesomeric betaines has been studied. The cross-conjugated thiazinium betaine 317 underwent 1,4-dipolar cycloaddition with electron-rich dipolaro-philes, and thus 1-diethylaminoprop-l-ine gave the pyrido[l,2-tf]pyrimidine 318 by loss of carbonyl sulfide (Equation 34). Reaction of 317b with 1,1-diethoxyethene resulted in the 8-ethoxy analogue of 318 (R = H) <1997JOC3109>. 

The most common method for the preparation of the fully aromatized pyrimidine skeleton is the condensation of an amidine with an a,P-unsaturated carbonyl compound. For example, Palanki and co-workers reported that the reaction of amidines 1 with a,P-unsaturated carbonyl compounds 2 produced pyrimidines 3 <00JMC3995>. 

Quinazolines undergo many of the same reactions as pyrimidines, such as the modification of an amino group. Gangjee and co-workers reported the reductive alkylation of diaminoquinazolinones 141 with various aryl carbonyl compounds 142, which regioselectively produced quinazolinones 143 <00JHC1097>. 

Fig. U.4 Reaction sequence showing how a small e.e. of the reagent is converted to a large e.e. of the product by a metal-assisted reaction. In the case shown, a 1 % e.e. of L-valine produced a 51 % e.e. of L-pyrimidine alcohol by the reductive asymmetric transfer of an isopropyl group from zinc to the carbonyl carbon of the...

The amino groups are replaced with oxygen. Although here a biochemical reaction, the same can be achieved under acid-catalysed hydrolytic conditions, and resembles the nucleophilic substitution on pyrimidines (see Section 11.6.1). The first-formed hydroxy derivative would then tautomerize to the carbonyl structure. In the case of guanine, the product is xanthine, whereas adenine leads to hypoxanthine. The latter compound is also converted into xanthine by an oxidizing enzyme, xanthine oxidase. This enzyme also oxidizes xanthine at C-8, giving uric acid. 

The pyrimidines cytosine and thymine both react with hydrazine, which initially attacks the unsaturated carbonyl system and then leads to ring opening. Again, base treatment is used to hydrolyse the phosphodiester bond. This reaction becomes selective for cytosine in the presence of NaCl, which suppresses reaction with thymine. 

In MCRs involving aminoazoles and carbonyl compounds, Meldrum s acid can also be used as reagent. The comprehensive review of the application of Meldrum s acid in the synthesis of pyridine and pyrimidine derivatives including reactions with aminoazoles was recently published [113]. In this connection, further we give only few selected facts concerning positional selectivity of such reactions. 

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