Compounds with Two Heteroatoms

We use the oxa-aza-thia system to name these compounds the suffixes -ole and -ine indicate five- and six-membered rings, respectively. When there is more than one kind of ring heteroatom, the atom of higher atomic number receives the lower number. 

Problem 20.34 Write the tautomeric structures of these pyrimidines. 

Problem 20.35 (a) What makes imidazole (Prob. 20.37a) aromatic (6) Explain why imidazole, unlike pyrrole, is basic. Which N is the basic site  

Catalytic reduction of the nitro group proceeds to the aniline (4-9). The chain is next extended by acylation of the newly formed amine with ortho-toluyl chloride (4-10) to give (4-11). Reduction of the azepinone carbonyl group with borohydride affords the vasopressin antagonist tolvaptan (4-12) [5]. 

A benzazepine that includes the same (3-ketoamide array as piroxicam (Chapter 11) retains NSAID activity. Oxidation of benzothiapinone (5-1), obtainable by cycli-zation of 4-(4-chlorophenylthio)-butyric acid, with hydrogen peroxide gives the corresponding sulfone (5-2). This is then converted to its enamine (5-34) by reaction with pyrrolidine. Condensation of the intermediate with 3,4-dichorophenylisocyanate (5-4) leads to the amide (5-5). Hydrolysis with an aqueous acid cleaves the enamine function to give the keto-amide and thus enolicam (5-6) [6]. 

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Compounds with two heteroatoms in one heterocyclic ring and one in another... 

Compounds with two heteroatoms are illustrated in Scheme 5. The oxazines and thiazines contain a saturated carbon atom the corresponding aromatic cations are oxazinium and thiazinium. 

For compounds with two heteroatoms joined to the same carbon, we used a 1,1-diX disconnection I removing one heteroatom to reveal a carbonyl compound, here an aldehyde, and a heteroatom nucleophile 2. Replacing the heteroatom by R2, we disconnect in the same way to reveal the same aldehyde and some nucleophilic carbon reagent 4, probably R2Li or R2MgBr. 

A compound with two heteroatoms in the ring 66, needed for a synthesis of mannicone 65, illustrates the other two oxidation states. Disconnecting both C-N bonds noting that C-l is at the acid oxidation level while C-3 is an enamine and so at the ketone oxidation level gives the keto-ester 67 and hydrazine 68. Where two heteroatoms are joined in a ring, it is usually better not to disconnect the bond between them but to look for a starting material containing both. 

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