Pyrimidines, 5-nitro-, reaction with

Nitration of 2-substituted 4/7-pyrido[l,2- ]pyrimidin-4-ones with 99% HN03 in cone. H2S04 gave 3-nitro derivatives <2000BMC751, 2001H(55)535>. Mannich reaction of 2-hydroxy-4//-pyrido[l,2-tf]pyrimidin-4-one afforded... 

The reaction of 2-amino-l-methylimidazole hydrochloride and EMME by heating in boiling ethanol in the presence of excess triethylamine overnight gave imidazo[l,2-tf]pyrimidine-6-carboxylate (1115, R = H) in 47% yield [82IJC(B)1030]. The similar reaction with 5-nitro-2-amino-1-methyl-imidazole yielded only a condensation product (1114, R = N02), which... 

Chloro, 3-bromo, 3-iodo, and 3-nitro derivatives of 5,7-dimethyl-pyrazolo[l,5-a]pyrimidine derivatives were prepared by chlorination, bromination, iodination, and nitration of 3-unsubstituted 5,7-dimethyl-pyrazolo[l,5-a]pyrimidines. Reaction with bromine and potassium thiocyanate gave a 3-thiocyanato derivative, which was converted into the mercapto derivative upon saponification. Nitrosation gives the 3-nitroso derivative and acylation with trifluoroacetic anhydride affords the trifluoroacetyl derivative (74JMC645 77JMC386). 

The amino moiety of the 3-carbohydrazide group of unsaturated and 6,7,8,9-tetrahydro-4-oxo-47/-pyrido[l,2-n]pyrimidine-3-carbohydrazides was condensed with acetone and 5-nitro-2-furoaldehyde (830MR687 88EUP252809). The reaction of 6-methyl-6,7,8,9-tetrahydro-4-oxo-4//-pyrido[l,2-a]pyrimidine-3-carbohydrazide with diethyl 2-[2-dimethyl-amino)vinyl]-6-methylpyridine-3,5-dicarboxylate in boiling ethanol for 4 hours afforded N-( 1,6-naphthyridin-6-yl)-4-oxo-4//-pyrido[ 1,2-a]pyrimi-dine-3-carboxamide 426 (85MIP1). 

Hydroxy-2-methyl-4//-pyrido[ 1,2-a]pyrimidin-4-one 365 gave 8-sub-stituted derivatives in a reaction with different electrophilic reagents (Scheme 28) (92KGS1660). Nitration gave 8-nitro-9-hydroxy-2-methyl-pyridopyrimidin-4-one 326. Reaction with iodine afforded 8-iodo-... 

Uracil derivatives can be nitrated at C-5 under conditions that allow retention of a sugar residue at N-1 Nitration at N-3 can also be achieved N-3-nitro-compounds react with amines via an ANRORC mechanism, with displacement of nitramide and incorporation of the amine as a substituted N-3, as shown below. This seqnence has been ntilised to prepare N-3-labelled pyrimidines (31.2.2). An analogous ANRORC process takes l-(2,4-dinitrophenyl)-uracils to 1-arylamino-uracils by reaction with arylamines at room temperatnre. ... 

Methyl-5-nitro-4-pyrimidinone has been reported to undergo nucleophilic type ring transformations on reaction with cycloalkanones in the presence of ammonium acetate to give 4,5-disubstituted pyrimidines and 5,6-disubstituted 3-nitro-2-pyridones (Scheme 206). ... 

Although predicted theoretically some years ago, unequivocal experimental evidence for the so-called oxa-benzidine rearrangement is still awaited. However, to the list of reactions suspected of involving this type of rearrangement must now be added the process outlined in Scheme 50, which is useful for the direct arylation of pyrimidine. Similar reactions occur with 2-chloro-3-nitro-pyridine and with 2-chloropyrazine, but not with 2-chloro- or 2-fluoro-pyridine. 

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-... 

Extension of this work by studying the reaction of 3-methyl-5-nitro-pyrimidin-4(3//)-one with -X-arylketones in the presence of ammonium acetate surprisingly revealed the formation of a mixture of 4-arylpyrimidines and 6-arylpyridin-2(l//)-ones (00JCS(P1)27). The ratio between pyridine and pyrimidine formation is dependent on the substituent X. With electron-donating substituents the formation of the pyridin-2(l//)-ones is favored, with electron-attracting substituents the formation of the pyrimidine derivatives (Scheme 21) In the formation of the 6-arylpyridin-2(l//)-ones the C-4- C-5-C-6 part of the pyrimidone-4 is the building block in the construction of the pyridine ring. Therefore, the pyrimidone can be considered as an activated o -nitroformylacetic acid (Scheme 21). 

Into a mixture of 1.6 g of 2-amino-4-methylpyrlmidine with 10 ml of glacial acetic acid is slowly added 2.13 g of concentrated sulfuric acid. A mixture of 2.4 g of 2-formyl-1-methyl-5-nitroimidazole in 20 ml of glacial acetic acid is slowly added to the mixture of the pyrimidine under stirring. The reaction mixture is maintained at a temperature of about 55°C for 4 hours. The resultant mixture is then diluted with 200 ml of distilled water and neutralized with a saturated aqueous solution of sodium bicarbonate. A brownish-yellow precipitate (MP 232° to 235°C) is formed and recovered. The product is analyzed by infrared spectroscopy and is found to conform to 2-amino-4-[2-(1-methyl-5-nitro-2-imidazolyI)vinyl] pyrimidine. 

---