NUCLEOPHILIC ATTACK ON RING CARBON ATOMS

Nucleophilic attack on ring atoms of large heterocycles is largely confined to saturated systems, saturated parts of partially unsaturated systems, and to carbonyl functions and the like. These reactions are not fundamentally different from those of corresponding acyclic systems, except for transannular reactions. 

In systems of proper geometry, nucleophiles within a side chain may be well connected for attack on ring atoms. For example, an aminomethyl group at the 5-position of a dibenzazepine-2-one was found to attack the carbonyl group (Section 5.16.3.5.2). Such reactions should be possible in rings of any size. 

Apparent nucleophilic attack on large, fully unsaturated rings may occur by way of attack on a valence tautomer, such as the reaction of oxepin with azide ion. Attack on the oxanorcaradiene valence tautomer leads to ring opening of the three-membered ring, and formation of 5-azido-6-hydroxy-l,3-cyclohexadiene (Section 5.17.2.2.4). 

---

Nucleophilic attack on the carbon atom of the carbonyl group, in reactions which lead to substitution rather than to ring opening, is discussed in this section. 

Nucleophilic attack on the carbon atoms of the 1,2,4-triazine ring is well-known and was discussed in detail in the previous review <84CHEC-I(3)369>. 

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. 

Oxygen nucleophiles usually attack a ring carbon atom rather than the sulfur atom of a thiirane, and those cases in which desulfurization is observed on treatment of a thiirane with oxygen bases probably involve the extrusion of sulfur by mechanisms other than a nucleophilic attack on sulfur, e.g. thermal. Desulfurization of thiirane intermediate (43)... 

Halide ions may attack 5-substituted thiiranium ions at three sites the sulfur atom (Section 5.06.3.4.5), a ring carbon atom or an 5-alkyl carbon atom. In the highly sterically hindered salt (46) attack occurs only on sulfur (Scheme 62) or the S-methyl group (Scheme 89). The demethylation of (46) by bromide and chloride ion is the only example of attack on the carbon atom of the sulfur substituent in any thiiranium salt (78CC630). Iodide and fluoride ion (the latter in the presence of a crown ether) prefer to attack the sulfur atom of (46). cis-l-Methyl-2,3-di-t-butylthiiranium fluorosulfonate, despite being somewhat hindered, nevertheless is attacked at a ring carbon atom by chloride and bromide ions. The trans isomer could not be prepared its behavior to nucleophiles is therefore unknown (74JA3146). 

In this simplified scheme (the participation of the adjacent zinc atom as the nucleophilic attack carrier is omitted), the formation of poly(propylene ether-carbonate) characterised by a regioregular head-to-tail structure is shown. This is possible because of the nucleophilic attack on the Cp atom of the neighbouring ring to that coordinating with its more basic oxygen atom to the metal atom. Actually, the predominant head-to-tail structure of the poly(propylene ether carbonate) obtained at 80 °C with the diethylzinc-pyrogallol-water (3 1 0.5) catalyst has been proved [146]. 

---