Nucleophilicity of bases

Nuclear magnetic resonance, 236 Nucleophiles, 35, 44, 47 Nucleophilic displacement, 121 Nucleophilicity of bases. 121 Nucleophilic substitutions, aromatic, 215 Nylon 6 and 66, 360... 

The high nucleophilicity of sulfur atoms is preserved, even if it is bound to electron withdrawing carbonyl groups. Thiocarboxylales, for example, substitute bromine, e.g. of a-bromo ketones. In the presence of bases the or-acylthio ketones deprotonate and rearrange to episulfides. After desulfurization with triphenylphosphine, 1,3-diketones are formed in good yield. Thiolactams react in the same way, and A. Eschenmoser (1970) has used this sequence in his vitamin B]2 synthesis (p. 261). 

The nucleophilicity of amine nitrogens is also differentiated by their environments. In 2,4,5,6-tetraaminopyrimidine the most basic 3-amino group can be selectively converted to a Schiff base. It is meta to both pyrimidine nitrogens and does not form a tautomeric imine as do the ortho- and /xira-amino groups. This factor is the basis of the commercial synthesis of triamterene. 

Typical nucleophiles known to react with coordinated alkenes are water, alcohols, carboxylic acids, ammonia, amines, enamines, and active methylene compounds 11.12]. The intramolecular version is particularly useful for syntheses of various heterocyclic compounds[l 3,14]. CO and aromatics also react with alkenes. The oxidation reactions of alkenes can be classified further based on these attacking species. Under certain conditions, especially in the presence of bases, the rr-alkene complex 4 is converted into the 7r-allylic complex 5. Various stoichiometric reactions of alkenes via 7r-allylic complex 5 are treated in Section 4. 

The nucleophilic reacbvity of the C-5 oxygen is well documented however, no quantitative data are available. A-2-Thiazoline-5-ones (212) react at oxygen with acetyl chloride or acetic anhydride (447. 452). benzoyl chloride (447). methyl or phenyl isocyanate (467). carbamoyl chloride (453, 467). or phosphorus derivatives (468, 428) in the presence of bases to give 213, 214, 215. or 216 (Scheme 109). Strong bases such as... 

The mechanism of this reaction is outlined m Figure 17 8 It is analogous to the mech anism of base catalyzed hydration m that the nucleophile (cyanide ion) attacks the car bonyl carbon m the first step of the reaction followed by proton transfer to the carbonyl oxygen in the second step... 

Both the basicity and the nucleophilicity of amines originate m the unshared electron pair of nitrogen When an amine acts as a base this electron pair abstracts a... 

There are three general reactions of perfluoroepoxid.es pyrolyses (thermal reactions), electrophilic reactions, and by far the most important, reactions with nucleophiles and bases. 

A AlI lation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nucleophilicity of the resulting indole anion. Conditions which typically result in A/-alkylation are generation of the sodium salt by sodium amide in Hquid ammonia, use of sodium hydride or a similar strong base in /V, /V- dim ethyl form am i de or dimethyl sulfoxide, or the use of phase-transfer conditions. 

The importance of this group of reactions to the chemistry of isoxazoles is shown by the considerable amount of effort expended on this topic (63AHC(2)365,79AHC(25)147). The lability of the isoxazole nucleus towards nucleophiles and bases distinguishes this heterocycle from other azoles. The conditions which lead to ring cleavage are quite varied and depend on the position and the nature of the substituents. 

The term nucleophilicity refers to the effect of a Lewis base on the rate of a nucleophilic substitution reaction and may be contrasted with basicity, which is defined in terms of the position of an equilibrium reaction with a proton or some other acid. Nucleophilicity is used to describe trends in the kinetic aspects of substitution reactions. The relative nucleophilicity of a given species may be different toward various reactants, and it has not been possible to devise an absolute scale of nucleophilicity. We need to gain some impression of the structural features that govern nucleophilicity and to understand the relationship between nucleophilicity and basicity. ... 

For the other broad category of reaction conditions, the reaction proceeds under conditions of thermodynamic control. This can result from several factors. Aldol condensations can be effected for many compounds using less than a stoichiometric amount of base. Under these conditions, the aldol reaction is reversible, and the product ratio will be determined by the relative stability of the various possible products. Conditions of thermodynamic control also permit equilibration among all the enolates of the nucleophile. The conditions that permit equilibration include higher reaction temperatures, protic solvents, and the use of less tightly coordinating cations. 

Krespan ° has prepared a number of macrocycles, having both aza- and oxa-linkages in them, based on the 3,3-dimethyleneoxetane unit (see also Sect. 8.4 and Eq. 8.12). Typically, 3,3-bis(chloromethyl)oxetane is treated with a diol as shown in Eq. (3.40), in the presence of base. Once the bicyclic system is formed, further treatment with other nucleophiles (e.g., ammonia) can lead to opening of the 4-membered ring. 

It was pointed out earlier that the low nucleophilicity of fluoride ion and its low concentration in HF solutions can create circumstances not commonly observed with the other halogen acids. Under such conditions rearrangement reactions either of a concerted nature or via a true carbonium ion may compete with nucleophilic attack by fluoride ion. To favor the latter the addition of oxygen bases, e.g., tetrahydrofuran, to the medium in the proper concentration can provide the required increase in fluoride ion concentration without harmful reduction in the acidity of the medium. 

Mechanism of Base-Catalyzed Hydration The base-catalyzed mechanism (Figure 17.5) is a two-step process in which the first step is rate-detennining. In step 1, the nucleophilic hydroxide ion attacks the carbonyl group, forming a bond to carbon. An alkoxide ion is the product of step 1. This alkoxide ion abstracts a proton from water in step 2, yielding the geminal diol. The second step, like all other proton transfers between oxygen that we have seen, is fast. 

Kevin and co-workershave developed nucleophilicity scales based on the solvolysis of cationic substrates R-X, the leaving group being neutral rather than anionic. Their/V ,jO+ scale is defined in Eq. (8-72). 

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