Ring opening nitrogen nucleophiles

Reactions (3) and (4) are openings of the epoxide ring by nitrogen nucleophiles. 

Aluminum chloride [7446-70-0] is a useful catalyst in the reaction of aromatic amines with ethyleneknine (76). SoHd catalysts promote the reaction of ethyleneknine with ammonia in the gas phase to give ethylenediamine (77). Not only ammonia and amines, but also hydrazine [302-01-2] (78), hydrazoic acid [7782-79-8] (79—82), alkyl azidoformates (83), and acid amides, eg, sulfonamides (84) or 2,4-dioxopyrimidines (85), have been used as ring-opening reagents for ethyleneknine with nitrogen being the nucleophilic center (1). The 2-oxopiperazine skeleton has been synthesized from a-amino acid esters and ethyleneknine (86—89). 

The pyrazole molecule resembles both pyridine (the N(2)—C(3) part) and pyrrole (the N(l)—C(5)—C(4) part) and its reactivity reflects also this duality of behaviour. The pyridinic N-2 atom is susceptible to electrophilic attack (Section 4.04.2.1.3) and the pyrrolic N-1 atom is unreactive, but the N-1 proton can be removed by nucleophiles. However, N-2 is less nucleophilic than the pyridine nitrogen atom and N(1)H more acidic than the corresponding pyrrolic NH group. Electrophilic attack on C-4 is generally preferred, contrary to pyrrole which reacts often on C-2 (a attack). When position 3 is unsubstituted, powerful nucleophiles can abstract the proton with a concomitant ring opening of the anion. 

Very little is known about nucleophilic attack on an unsubstituted carbon atom of pyrazoles and their aromatic derivatives (pyrazolones, pyrazolium ions). The SwAr reaction of halogenopyrazoles will be discussed in Section 4.04.2.3.7. Sulfur nucleophiles do not attack the ring carbon atoms of pyrazolium salts but instead the substituent carbon linked to nitrogen with concomitant dequaternization (Section 4.04.2.3.lO(ii)). The ring opening of pyrazolium salts by hydroxide ion occurs only if carbon C-3 is unsubstituted the exact mechanism is unknown and perhaps involves an initial attack of OH on C-3. 

The reaction of 2-phenyl-l-azirine (201) with benzoic acid gaveN-benzoylphenacylamine (204) (67BCJ2938). The overall mechanism of the reaction involves initial protonation on nitrogen followed by addition of the nucleophile to the azirinium ion and finally ring opening. 

The suggested reaction mechanism involves a nucleophilic attack of the imine nitrogen at the activated triple bond, followed by a proton exchange, to give a benzimidazolinium system which, by intramolecular attack at the carbonyl group, leads to an epoxide that ring opens to the observed product. For the ethyl derivative (R = Et) a tub conformation could be established by X-ray crystallographic analysis.33... 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

---