2.6- diamino nitrosation

Instead of sodium nitrite, isoamyl nitrite is sometimes used as a nitrosating agent in synthesis of the benzotriazole ring. With this reagent, the reaction conditions are very mild allowing survival of acid sensitive groups. In an example of such a reaction, methyl 3,4-diamino-2-methoxybenzoate 1286 is treated with isoamyl nitrite at room temperature. The reaction is fast and provides methyl 4-methoxybenzotriazole-5-carboxylate 1287 in 62% yield, isolated by simple filtration off the precipitate (Equation 31) <2006JME4762>. 

Amino acids undergo similar nitrosation reactions to yield hydroxy acids or lactones. Diamino acids tend to yield cyclic imino acids, so that ornithine and lysine give rise to proline and pipecolic acid, respectively. 

Ji, X.-B., and Hollocher, T. C. (1988a). Mechanism for nitrosation of 2,3-diamino-naphthalene by Escherichia coli Enzymatic production of NO followed by 02-dependent chemical nitrosation. Appl. Environ. Microbiol. 54, 1791-1794. 

The F-triazole ring in the pyrazolol 3,4-d)-i -triazole (90) was generated by nitrosation of 4,5-diamino-3-methyl-l-phenylpyrazole.86... 

Amino-oxy-pyrimidines, and amino-dioxy-pyrimidines can be C-nitrosated, and such 5,6-dinitrogen-substituted pyrimidines, after reduction to 5,6-diamino-pyrimidines, are important intermediates for the synthesis of purines (an example is shown below see also 27.11.1.1) and pteridines (14.14). 

Nitrosation takes place in the benzenoid 5-position in pyrimidines with three strongly electron-donating groups, e.g., 0x0, thioxo, or amino groups. In disubstituted pyrimidines, the relative positions of the substituents are decisive for any reaction 4,6-diamino- and 4,6-dihydroxy-pyrimidines are 5-nitrosated whereas their 2,4-isomers fail to react. Nitrosation is brought about by nitrous acid or by nitrite esters. When the reaction is slow, an alkyl substituent may be nitrosated on the a-carbon the product is an oxime. An extensive review on nitrosopyrimidines is available [Pg.120]

Nitrosation of 3,5-diamino-27/-l,2,6-thiadiazine 1,1-dioxides 138 and 5-amino-3-oxo-3,4-dihydro-2//-l,2,6-thiadia-zine 1,1-dioxides 140 provided the 4-nitroso derivatives 139 (58-96%) and 4-hydroxyimino compounds 141 (50 94%), respectively (Scheme 6) <1996J(P2)293>. 

The work began with the condensation of urea with ethyl cyanoacetate. The product, cyanoacetylurea on treatment with dilute, warm sodium hydroxide (NaOH) generated 4-aminouracil (4-amino-2,6-dioxypyrimidine). Nitrosation of the sulfate salt with sodium nitrite produced the corresponding isonitroso derivative, which underwent easy reduction (with ammonium sulfide) to the corresponding 5,6-diaminouracil (4,5-diamino-2,6-dioxypyrimidine). 

As shown in Scheme 14.1, guanidine hydrochloride [H2NC(NH2)NH2 Cl ] was converted to the free base with sodium ethoxide in ethanol. After the precipitated sodium chloride was removed, the solution was treated with ethyl cyanoacetate.The product of the condensation reaction, on heating (and also on treatment with aqueous base), underwent cychzation to produce 2,4-diamino-6-oxypyrimidine. On nitrosation, followed by reduction (with ammonium sulfide, (NH4)2S), the corresponding 2,4,5-triamino-8-oxopyrimidine resulted and the reaction of the pyrimidine with sodium formate and formic acid yielded guanine (G), indistinguishable from the authentic material. 

Cyclocondensations with simultaneous involvement of two functional groups 6-Amino [6- C]uracil (175. see above) is also readily accessible through cyclocondensation of ethyl [ CJcyanoacetate with urea. Subsequent two-step amination through nitrosation and reduction of the nitroso group converted 175 into 5,6-diamino[6- C]uracil. Heating of this intermediate with urea provided [4- C]uric acid (IM) in an overall radiochemical yield of 48% (Traube synthesis) . When formamide was employed in the last step, [4- C]-... 

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