Pyrimidines, -fused, ring-opening

Pyrazoles can be prepared by ring opening reactions of fused systems already containing the pyrazole nucleus. Thus several [5.5], [5.6] and [5.7] fused heterocycles have been opened to substituted pyrazoles, usually in basic medium. In general, the method has little preparative interest since another pyrazole derivative has usually been used to build the ring-fused system. However, due to the unexpected structures obtained, two publications are worthy of notice. 6//-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine (638) was readily obtained from the corresponding pyrazolopyrimidine by the action of diazomethane at room temperature (Scheme 59) (81H(15)265). When (638) was treated with potassium hydroxide, the pyrazole (640) was formed, probably via the diazepine (639). 

E. C. Taylor and his co-workers have demonstrated an important principle in the ring-opening of pyridopyrimidines and other fused pyrimidine systems to o-aminonitriles. They have demonstrated that based-catalyzed cleavage of a 4-substituted pyrimidine will occur provided that (a) the anion formed by the attack by the base at the 2-position can be stabilized by appropriate structural features in the remainder of the molecule and (b) that the substituent attached to the 4-position is capable of departure with its bonding pair of electrons in... 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Ring opening of also a fused [l,2,4]triazole system by secondary amines has been reported. Chupakhin et al. described that 5-methyl-6-nitro[l,2,4]triazolo[l,5-r ]pyrimidin-7(8/f)one 122 underwent ring opening when treated with various secondary amines to yield pyrimidyl ureas 123 in medium to good yield <2001IZV655>, as shown in Scheme 14. 

Pyrimidines have been obtained after transformation of other monoheterocycles, or from fused pyrimidine heterocycles in reactions in which the pyrimidine ring is set free in ring-opening or elimination reactions. 

When 1,2,5-thia- and selena-diazolo[3,4- pyrimidine-5,7-dione W-oxides are treated with sodium hypochlorite, the respective S or Se atom is replaced by O to give 1,2,5-oxadiazoles, as shown in Scheme 82 (precise yields not given) <2000CHE1359>. A more vigorous oxidation leads to ring-opening of the fused five-membered ring (see Section 10.13.5.4). 

Nucleophilic substitution in the azine ring is a normal reaction. The fused oxazole ring, however, is susceptible to nucleophilic ring opening reactions, especially in oxazolium salts and dihydro derivatives. When fused to pyrimidine, substituents in the pyrimidine ring may promote a Dimroth rearrangement of the latter. 

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