N-Linked Substituents

A-(Monosubstituted amino)pyridiniums (972) are in prototropic equilibrium with A-imides (973) and dications (971). For R = H or allyl, the A-imides (973) are very strong bases and cannot usually be isolated if R is an electron-withdrawing group (e.g. acyl, sulfonyl, nitro), then the imide (973) is less basic and more stable. The cations (971) are only obtained in very strongly acid media. 

A-Aminopyridinium cations can be acylated or sulfonylated (with acid halides) and nitrated (H2S04 - HN03) to give the corresponding -(substituted amino)pyridines (972), often isolated as the imides (973 R = COR, S02R or N02). 

Both the NH2 protons in (974) can be replaced by electrophiles in this way e.g. with hexane-2,5-dione the A-(pyrrol-l-yl)pyridinium (975) is formed. 

Aldehydes readily yield imines, cf (976), and aryldiazonium salts form aryl azides and pyridine, presumably via ArN = N- N-Py+. Nitrous acid and A-aminopyridinium cations yield pyridine and 

A-Aminopyridones can be oxidized to nitrenes. Thus, 3-amino-1,2,3-benzotriazin-4-ones (977) with lead tetraacetate lead to an intermediate nitrene (978), which can lose one or two molecules of nitrogen. 

As would be anticipated, amino groups in the homocyclic ring of 1,2-benzisoxazoles behave as normal aromatic amines, forming mono- and bis-acyl derivatives, etc. (67AHC(8)277,p. 296). In th e isomeric 2,1-benzisoxazoles the 3-amino compound exists as such and not in the tautomeric 3-imino form (65CB1562). Amino groups in 3-phenyl substituents behave as normal aromatic amines (67AHC(8)277,p. 331). 

3-Amino-l,2-benzisoxazoles which are stable to acids and bases can be diazotized in acetic acid, usually giving 3-hydroxy compounds. 

Other amino substituted isoxazoles undergo ring-opening reactions on treatment with base. Thus the amidine derivative (249) gave the triazole (250) (64TL149), while the triazene (251) on reaction with ammonia gave the tetrazole (252) (64X461). 

Nitro groups in the homocyclic ring of 1,2-benzisoxazoles have been reduced to the corresponding amino groups without opening of the isoxazole nucleus. SnCU/HCl and Adam s catalyst/H2 have both proved effective in this respect. Similar behavior was observed for nitro groups in the isomeric 2,1-benzisoxazoles (67AHC(8)277,pp.295,33l). 

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N-Linked substituents O-Linked substituents S-Linked substituents C-Linked substituents Reactivity at the Ring Nitrogen Atoms Reduction Oxidation... 

N-Linked Substituents (Nitro and Amino Compounds and Azides)... 

REACTIVITY OF SUBSTITUENTS ATTACHED TO RING HETEROATOMS 4.09.8.1 N-linked Substituents... 

We will survey the reactions of N-linked substituents classified by the atom attached to the cyclic nitrogen. Unlike heterocyclic C-substituents, where the benzene prototype and the carbonyl analogy link much of the typical chemical behavior to familiar compounds, no simple model exists for N-substituents. However, certain trends are clear. The existence of the positive pole in cations of type (922) ensures that nucleophilic attacks (a)-(d) are the most important of the following reaction types, many of which occur for several of the different classes of N-substituents. 

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