Nitroso derivatives

The nitrosation of pyrroles and indoles is not a simple process. The 3-nitroso derivatives (84) obtained from indoles exist largely in oximino forms (85) (80IJC(B)767). Nitrosation of pyrrole or alkylpyrroles may result in ring opening or oxidation of the ring and removal of the alkyl groups. This is illustrated by the formation of the maleimide (86) from 2,3,4 -trime thylpyrrole. 

Treatment of 4-hydroxy-l-phenyl-l,8-naphthyridin-2-(lH)-one (76) with sodium nitrite gave the 3-nitroso derivative (77), which could be oxidized to 4-hydroxy-3-nitro-l-phenyl-l,8-naphthyridin-2(lH)-one (30a) (94SC3289). According to the authors, this method of preparing (30a) is more convenient for large-scale preparation than the one using A-phenyl-3-azaisatoic anhydride as starting material (see Section II,A,4,a) [(29a) (30a)]. 

The 3-amino group of 3,4-diamino-2//-pyrido[l,2-u]pyrimidin-2-ones 216, obtained from 3-nitroso derivatives by reduction with Na2S204 in 30% NH4OH at 70-80 °C, was acylated with acyl chlorides, and the acylated products 217 were cyclized to pyrido[2,l-Z)]purin-10-ones 218 by treatment with NaOMe (95JHC1725). 

Mendeleyev J, Kirsten E, Hakam A et al (1995) Potential chemotherapeutic activity of 4-iodo-3-nitrobenzamide metabolic reduction to the 3-nitroso derivative and induction of cell death in tumor cells in culture. Biochem Pharmacol 50 705-714... 

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). 

Diaminopyridine with nitrous acid forms the 3-nitroso derivatives. Nitrosation of pyrimidines occurs readily in the presence of three electron-releasing substituents pyrimidine-4,6-diamine is also nitrosated to the blue 5-nitroso derivative. 

Nitroso derivatives (120) are obtained from indoles they exist largely in oximino forms (121) (80IJC(B)767). The N-nitrosation of 5-chloroindole is followed by a migration of the nitroso group from N to C-3, to give an indolenine-3-oxime (122) hydrolysis and recyclization leads to a indazole carbaldehyde (123) (86JA4115). 

Nitrosation of 2-amino-4//-pyrimido[2,l-u]isoquinolin-4-ones (151, R1 = H) in acetic acid with sodium nitrite at 70°C gave 2-amino-3-nitroso derivatives (151, R1 = NO) (73GEP2261009). Bromination of 2-methyl-4//-pyrimido[2,l- ]isoquinolin-4-one (32 = Me) with N-bromosuccin-imide in boiling chloroform for 1 h yielded 3-bromo derivative 152 in 96% yield (80KGS1656). 

Upon reaction with nitrous acid, indole produces a complex mixture of products. In addition to 3-oximino-3H -indole (16), which is the stable tautomeric form of 3-nitrosoindole (17), dimeric products of the type (18) and (19) are also formed. In contrast, (16) appears to be the sole product of the nitrosation of indole with amyl nitrite and sodium ethoxide (72HC(25-2)537). Studies of the nitrosation of pyrrole are somewhat indecisive. The mononitrosopyrrole, obtained from the reaction of pyrrole with nitrous acid, has not been fully characterized, but there is some evidence that nitrosation of pyrrole with amyl nitrite and sodium ethoxide leads to the sodium salt of the 3-nitroso derivative. However, upon the addition of acid, the product rearranges to give the oxime of 3-formylisoxazole (20) (B-77MI30502). 

PhenylpyrroIo[2,3-6]pyridine gives the 3-nitroso derivative (40) with nitrous acid... 

Reduction of 3-nitroso derivative 329 by treatment with activated zinc dust in boiling acetic acid for 6 hours gave 3-amino derivative 330 [91IJC(B)839]. 2,3-Diamino-4//-pyrido[ 1,2-a]pyrimidin-4-one was pre-... 

Nitrosation of malonyl-a-aminopyridine (37) in 2 N hydrochloric acid at 0°C with a 1 N aqueous sodium nitrite afforded the 3-nitroso derivative 329 [91IJC(B)839]. 2-Amino-3-nitroso-4//-pyrido[l,2-a]pyrimidin-4-one was prepared from 2-amino-4//-pyrido[l, 2-a]pyrimidin-4-one by treatment of 1 N sodium nitrite in 2 N hydrochloric acid at 0°C for 30 minutes (92MI23). 

The nitrosation of 2-methyl-5-phenylpyrrole yields the 3-nitroso derivative predominantly (60%) together with the 4-nitroso product (30%) [71 AC(R)237]. 

Two amino groups activate the pyridine nucleus sufficiently that nitrosation can take place 2,6-diaminopyridine (30) reacts with nitrous acid in sulfuric or acetic acid to give the 3-nitroso derivative (31),8°, 8 ... 

Unlike nitration, C-nitrosation cannot be forced at elevated temperatures because of the lability of nitrous acid. Thus nitrosation must be done at or below room temperature, and this requires the substrate to have a free unactivated position as well as at least two electron-releasing substituents. These criteria are met by 4-hydroxy-1-phenyl-l,8-naphthyridin-2( 1 //)-one (10, R = H), which does yield its 3-nitroso derivative (10, R = NO) (NaN02, AcOH, H20, 20°C 96%).892... 

Nitrosation. 2,6-Diaminopyridine with nitrous acid forms the 3-nitroso derivatives. Nitrosation has been much used in pyrimidine chemisty nitrosation of pyrimidines occurs readily in the presence of three electron-releasing substituents pyrimidine-4,6-diamine is also nitrosated to the blue 5-nitroso derivative treatment of 4-amino-2,6-dimethoxypyrimidine 137 with isoamyl nitrite in DMSO at room temperature gives the 5-nitroso derivative 138 in 75% yield <2002SL255>. 

Reflux it for 3 hours with AC2O, then fiacrionally distil it, preferably under reduced pressure. The 3-nitroso derivative has m 72.5" (green crystals from petroleum ether/ C6H6). [Klaassens School Rec Trav Chim Pays Bos 48 1272 1929.]... 

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