5- Nitro-2-phenylpyrimidine

Besides quaternary pyrimidinium salts, pyrimidines with a strong electron-withdrawing substituent on one of the carbons of the pyrimidine ring show enhanced reactivity of the heterocyclic ring toward nucleophiles. In light of the results mentioned previously with pyrimidinium salts, it is not too surprising that reflux of an ethanolic solution of 5-nitropyrimidine with benzamidine hydrochloride or pivalamidine hydrochloride in the presence of triethylamine afforded 5-nitro-2-phenylpyrimidine (108, 84%... 

Other workers confirmed the above results but did not isolate any of the 4-nitrophenyl product. The nitration of 5-bromo and 5-chloro-2-phenylpyrimidine was also shown to yield the ortho and meta products (in the ratio of about 3 7) with no para isomer being observed (80H1989). Further work has indicated that 5-nitro-2-phenylpyrimidine undergoes nitration in mixed acid at 0°C to give a similar mixture of ortho and meta products (1 7) with no para isomer, whereas 6-methyl-2-phenylpyrimidin-4-one (72) forms only a 3-nitro phenyl product (91UP1). 

Dimethoxy-5-nitro-2-phenylpyrimidine heated 15 min. at 200° without solvent anhydro -4- hydroxy -1,3- dimethyl - 5 - nitro -6- oxo-2- phenylpyrimidinium hydroxide. Y 80%. F. e. s. Y. Maki, M. Sako, and M. Suzuki, Chem. Commun. 1972, 999. 

These results seem to indicate that there are two pathways leading to the nitro products for the 2- and 4-phenylpyrimidines. Nitration of the free base, or of the protonated heterocycle, leads to meta nitration. However, if an N-nitro intermediate is formed, which can undergo intramolecular nitration in a solvent cage, then ortho attack results (Fig. 12). 

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