O-Linked Substituents

1-Hydroxypyridinium ions (985) readily lose a proton to give A-oxides A-oxides are themselves weak bases which form 1-hydroxypyridinium ions by proton addition. 

Pyridine 1-oxides possess a unique pattern of reactivity  

Reduction of A-oxides affords the parent heterocycle and can be achieved by  

Certain pyridazine iV-oxides are isomerized into the corresponding diazoketones, e.g. (994) — (995) ring contraction to the corresponding furan (996) can then occur. 

Phenazine 9,10-dioxide (997) is converted by irradiation in benzene to the 1,6-oxidoannulene (999) via (998) and an oxygen walk (82AHC(30)253). 

3-Hydroxy-l,2-benzisoxazoles show a variety of reactions. With POCla/EtaN the 3-chloro compound is formed (see Section 4.16.3.3 for further discussion). 

In contrast to the 3-amino derivatives, 3-hydroxy-2,l-benzisoxazoles are relatively labile. With nitrous acid they undergo ring fission to anthranilic add. Its 3-acetoxy derivative (258) reacts with primary amines to form the quinazolone (259) (67AHC(8)277, p. 297). 

3-Alkoxy-2,l-benzisoxazole-4,7-diones undergo ready nucleophilic displacement of the 3-alkoxy substituent, yielding 3-alkylamino and 3-dialkylamino derivatives with primary and secondary amines, respectively (67TL4313). In this instance the 4-carbonyl group apparently provides an activating effect. 

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

In general, 3-hydroxy-l,2,4-thiadiazoles react with hard nucleophiles (acid chlorides, sulfonyl chlorides) at the oxygen atom, whereas soft nucleophiles (isocyanates, acid anhydrides) react at the N-2 position yielding 1,2,4-thiadiazolin-3-ones. Nucleophiles react at the N-4 position of 5-hydroxy-l,2,4-thiadiazoles <1996CHEC-II(4)307>. There have been no new publications on O-linked substituents since the publication of CHEC-II(1996). 

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