The ‘t‐Amino Effect’ of ortho‐Nitroso Amines. Synthesis of 2,6‐Diaminoadenine Derivatives from 6‐(Dialkylamino)‐5‐nitrosopyrimidines

Abstract

The ‘t‐amino effect’ of amino‐nitroso compounds was documented by preparing the (dialkylamino)‐nitroso pyrimidines 4–18, and cyclising them under thermal conditions in high yields to the purine derivatives 19–32. The reactivity of the amino‐nitroso‐pyrimidines, particularly of 17 derived from diethyl iminodiacetate, and of 19, derived from 1‐phenylimidazolidine, correlates with the stability of the intermediate azomethine ylide. Thermolysis of the amino‐nitroso‐pyrimidines 34–37, possessing dialkylamino substituents at C(4) and C(6), proceeded by protiodenitrosation, leading to 38–41.

One- or Two-Step Synthesis of C-8 and N-9 Substituted Purines

“…The second route starts from pyrimidines (pathway 2). − This well-established strategy provides 8,9-disubstituted purines either by the reaction of pyrimidine-4,5-diamines with orthoesters , or acyl chlorides or by refluxing 5-nitropyrimidin-4-amines in phenyl ether . However, the structure of the synthesized purine (R′ and R′′) is limited to the nature of the starting pyrimidine.…”

“…Compound 17 (yield = 47%, 235 mg from 420 mg (1.9 mmol) of 3) was isolated as a beige solid; mp >250 °C. 6-Amino-8-butyl-9-phenylethyl-3,9-dihydro-2H-purin-2-one (18). The precipitate was washed in hot acetonitrile.…”

2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides

“… While direct deprotonation of imines 294 (R 1 = H) typically affords a 2-azaallyl anion, the corresponding N-protonated azomethine ylides ( 289 ) can be accessed via a 1,2-prototropic rearrangement of imines 294 , as was pioneered by Grigg − and utilized by many others (Scheme ). − Other prototropic events, such as 1,5- and 1,6-shifts, also can lead to the generation of reactive azomethine ylides. , In the presence of chiral Brønsted acid catalysts, this 1,2-protropic event and the ensuing cycloaddition with appropriate dipolarophiles can be rendered highly diastereo- and enantioselective. − Similarly, proline-based organocatalysts which activate α,β-unsaturated carbonyl dipolarophiles can affect a highly asymmetric 1,3-dipolar cycloaddition with azomethine ylides generated via 1,2-prototropy or deprotonation. − A special situation championed by Seidel involves the carboxylate-mediated transient generation of an azomethine ylide as part of imine isomerization event. − For example, condensing pyrrolidine with 2,6-dichlorobenzaldehyde in the presence of terminal alkynes and a Cu­(II) dicarboxylate catalyst resulted in the near-exclusive formation of 2-alkynylpyrrolidine derivatives 301 (Scheme ).…”

“…As outlined in Scheme 100, there are several different synthetic strategies for the generation of N-protonated azomethine ylides (289) and their N-alkylated cousins (290) including (1) ring-opening reactions, (2) deprotonation, (3) 1,2-prototropic rearrangement, (4) decarboxylation, (5) disilylation/destannylation, and (6) via carbenes and carbenoids. The most classical method involves the thermal (or photochemical) retropericyclic ring opening of aziridines (291). 200−224 The mechanism of this ring-opening process and the ensuing 1,3dipolar cycloaddtions have been investigated thoroughly.…”

“…285−289 Other prototropic events, such as 1,5and 1,6-shifts, also can lead to the generation of reactive azomethine ylides. 290,291 In the presence of chiral Brønsted acid catalysts, this 1,2-protropic event and the ensuing cycloaddition with appropriate dipolarophiles can be rendered highly diastereo-and enantioselective. 291−300 Similarly, proline-based organocatalysts which activate α,β-unsaturated carbonyl dipolarophiles can affect a highly asymmetric 1,3dipolar cycloaddition with azomethine ylides generated via 1,2prototropy or deprotonation.…”