Reactions of Ring Atoms with Nucleophiles

All examples of nucleophilic reactions have involved reducing agents A2-pyrazolines are common products. 

---

C. Reactions of Ring Atoms with Nucleophiles 1. Reducing Agents... 

Reaction of propylene oxide with nucleophiles in the presence of the zeolite, H-X, gave a mixture of products, 37 and 38. In contrast to the ring opening by methanol that was promoted by Nafion-H (Eqn. 22.35), when H-X was used as the catalyst the major product was that in which the nucleophile was found on the terminal carbon atom. Reaction of propylene oxide with ethanol... 

Nucleophilic reactivity of the sulfur atom has received most attention. When neutral or very acidic medium is used, the nucleophilic reactivity occurs through the exocyclic sulfur atom. Kinetic studies (110) measure this nucleophilicity- towards methyl iodide for various 3-methyl-A-4-thiazoline-2-thiones. Rate constants are 200 times greater for these compounds than for the isomeric 2-(methylthio)thiazole. Thus 3-(2-pyridyl)-A-4-thiazoline-2-thione reacts at sulfur with methyl iodide (111). Methyl substitution on the ring doubles the rate constant. This high reactivity at sulfur means that, even when an amino (112, 113) or imino group (114) occupies the 5-position of the ring, alkylation takes place on sulfiu. For the same reason, 2-acetonyi derivatives are sometimes observed as by-products in the heterocyclization reaction of dithiocarba-mates with a-haloketones (115, 116). 

The mechanism of the cycloaddition reaction of benzaldehyde 2a with Danishefsky s diene 3a catalyzed by aluminum complexes has been investigated theoretically using semi-empirical calculations [14]. It was found that the reaction proceeds as a step-wise cycloaddition reaction with the first step being a nucleophilic-like attack of Danishefsky s diene 2a on the coordinated carbonyl compound leading to an aldol-like intermediate which is stabilized by interaction of the cation with the oxygen atom of the Lewis acid. The next step is the ring-closure step, giving the cycloaddition product. 

Reactions at ring atoms consist mainly of electrophilic attack at nitrogen and cycloadditions. Examples of the reaction of 2-substituted 1,3,4-oxadiazoles with bifunctional compounds at both ring nitrogen and at the substituent, leading to cyclic systems, are included in Section 4.06.5.2 irrespective of where the initial point of attack took place. A few examples of nucleophilic attack at unsubstituted carbon are described, the more common nucleophilic attack at substituted carbon being included under reactions of the appropriate substituent (Sections 4.06.7.1-7.5). 

It is well known 113,14 20 25> that the addition of hydroxyl-containing compounds (water, alcohols, phenols, acids) considerably promotes the interaction of epoxy compounds with amines and other nucleophilic reagents. In this case, the epoxy ring carbon atom becomes more sensitive to nucleophilic attack. The reaction proceeds through a trimolecular transition state initially suggested by Smith26 27) for the reactions of epoxy compounds with amines2... 

This chapter covers reactions in which coordination of a transition metal to the ir-system of an arene ring activates the ring toward addition of nucleophiles, to give V-cyclohexadienyl-metal complexes (1 Scheme 1). If an electronegative atom is present in the ipso position, elimination of that atom (X in 1) leads to nucleophilic aromatic substitution (path a). Reaction of the intermediate with an electrophile (E+) can give disubstituted 1,3-cyclohexadiene derivatives (path b). If a hydrogen occupies the ipso posi-... 

In some cases, the function of the metal ion is more to deactivate alternative sites of reaction than to activate a particular atom towards attack by an electrophile. A good example of this is seen in the transamination reaction of ornithine (5.12) with urea. Co-ordination of the ornithine to copper(n) results in the formation of a five-membered chelate ring, leaving the amino group of the 3-aminopropyl substituent as the most nucleophilic site in the complex. Reaction of this complex with urea results in a transamination process and the formation of the copper(n) complex of the substituted urea, which is the amino acid citrulline (5.13) (Fig. 5-20). The complex may be demetallated to yield the free amino acid in respectable yields. 

A different synthetic approach to l-sila-2,4-diaza-3-oxocyclopentanes utilized the reaction of silenes 68 with ureas and afforded the heterocycles 69 in moderate yields (50-65%) (Equation 6). It was proposed that the reaction proceeds in two steps with the ring-forming process being the nucleophilic attack of the nitrogen atom at the carbon center <20030M1314>. 

Although the attack of nucleophiles upon aromatic rings in the gas phase was reported more than a decade ago, not many publications on this topic have appeared since then. Thus, it was shown in earlier work that alkoxide ions react with fluorobenzene to give F and with hexafluoro-benzene to give pentafluorophenoxide anions (Briscese and Riveros, 1975), that (M + N02) adducts can be formed from reaction of N02 with < -, m-and /7-dinitrobenzenes (Bowie and Stapleton, 1977) and that (M — H + 0) ions are generated in reactions of Ot ions with benzene, naphthalene, pyridine, alkylbenzenes, methylpyridines and fluorotoluenes by displacement of a ring hydrogen atom (Bruins et al., 1978). 

---