Basicity of nucleophiles

Wadsworth et al. (1983) has correlated the stereochemistry of substitution with basicity of nucleophile in the reaction of 2-chloro-l,3,2-dioxaphos-phorinanes with a number of nucleophiles. However, as Hall and Inch (1980b) emphasize, such trends can only be observed in the reactions of specific six-membered phosphorus species with specific nucleophiles. 

The rates of nucleophilic addition to carbonyl groups that you met in Chapter 6 depend on the basicity of nucleophiles. As nitrogen bases are much stronger than oxygen bases (or, if you prefer, ammonium ions are much weaker acids than H3O ), amines are also much better nucleophiles than water or alcohols. This is dramatically illustrated in an amide synthesis from aniline and acetic anhydride in aqueous solution. 

The high acidity of superacids makes them extremely effective pro-tonating agents and catalysts. They also can activate a wide variety of extremely weakly basic compounds (nucleophiles) that previously could not be considered reactive in any practical way. Superacids such as fluoroantimonic or magic acid are capable of protonating not only TT-donor systems (aromatics, olefins, and acetylenes) but also what are called (T-donors, such as saturated hydrocarbons, including methane (CH4), the simplest parent saturated hydrocarbon. 

The nucleophilicity of the nitrogen atom survives in many different functional groups, although its basicity may be lost. Reactions of non-basic, but nucleophilic urea nitrogens provide, for example, an easy entry to sleeping-pills (barbiturates) as well as to stimulants (caffeine). The nitrogen atoms of imidazoles and indole anions are also nucleophilic and the NH protons can be easily substituted. 

The reaction of amines with the 4-phenylazo derivative (228) results in their rearrangement into triazolines. Depending on the basicity of the amines and the size of the alkoxy group, three different triazolines (229. 230, and 231) are obtained (Scheme 117) (454. 459, 472). In all cases, the first step involves nucleophilic addition of the amine to the carbonyl group followed by ring opening and further ring closure. 

With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

Taking into account the previous discussion of the reactivities of simple halogenothiazoles or nitrothiazoles, the mechanism of nucleophilic reac tivity of 2-halogeno-5-nitrothiazoles with an excess of basic nucleophile such as CHjO can be proposed (Scheme 14). 

A second factor that can tip the balance m favor of substitution is weak basicity of the nucleophile Nucleophiles that are less basic than hydroxide react with both pri mary and secondary alkyl halides to give the product of nucleophilic substitution m high yield To illustrate cyanide ion is much less basic than hydroxide and reacts with 2 chlorooctane to give the corresponding alkyl cyanide as the major product... 

The noteworthy properties of amines are their basicity and their nucleophilicity The basicity of amines has been discussed m Section 22 4 Several reactions m which amines act as nucleophiles have already been encountered m earlier chapters These are sum marized m Table 22 4... 

This scheme eliminates the process of converting bis(etherimide)s to bis(ether anhydride)s. When polyetherimides are fusible the polymerization is performed in the melt, allowing the monamine to distill off. It is advantageous if the amino groups of diamines are more basic or nucleophilic than the by-product monoamine. Bisimides derived from heteroaromatic amines such as 2-arninopyridine are readily exchanged by common aromatic diamines (68,69). High molecular weight polyetherimides have been synthesized from various N,lSf -bis(heteroaryl)bis(etherimide)s. 

Equation 4 can be classified as S, , ie, substitution nucleophilic bimolecular (221). The rate of the reaction is influenced by several parameters basicity of the amine, steric effects, reactivity of the alkylating agent, and solvent polarity. The reaction is often carried out in a polar solvent, eg, isopropanol, which may increase the rate of reaction and make handling of the product easier. 

Isoxazolium salts can be prepared by reaction with alkyl iodides or sulfates, although the low basicity of isoxazoles and their sensitivity to nucleophilic attack may necessitate special care. Isoxazolium salts containing bulky Af-substituents can be prepared by the reaction of isoxazoles with alcohols in the presence of perchloric acid. For example, the reaction of 3,5-dimethylisoxazole (53) with some alcohols in the presence of 70% perchloric acid gave isoxazolium salts, (54a) in 29%, (54b) in 57% and (54c) in 82% yield 79AHC(25)147, 68JOC2397). Attempts to quaternize 3,5-dimethyl-4-nitroisoxazole failed 71JCS(B)2365). 

The 1-azirine ring also undergoes a number of reactions in which the heterocycle plays the role of the nucleophile. Although the basicity of the nitrogen atom in the azirine ring is much lower than in simple aliphatic amines, this system can still function as a nucleophilic reagent. One example of this involves the acid-catalyzed hydrolysis of 1-azirines to a-aminoketones (200) which represents a well-established reaction. In fact, in many reactions of 1-azirines where acid catalysis is used, formation of a-aminoketones is difficult to avoid (67JA44S6). 

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. ... 

The kinetics of the hydrolysis of some imines derived from benzophenone anc primary amines revealed the normal dependence of mechanism on pH with ratedetermining nucleophilic attack at high pH and rate-determining decomposition of the tetrahedral intermediate at low pH. The simple primary amines show a linear correlation between the rate of nucleophilic addition and the basicity of the amine Several diamines which were included in the study, in particular A, B, and C, al showed a positive (more reactive) deviation from the correlation line for the simple amines. Why might these amines be more reactive than predicted on the basis of thei ... 

Care must also be taken in the choice of rubber to insure that the rubber, or one of its additives, does not initiate the premature polymerization of the monomer. Even very low concentrations of a basic or nucleophilic material in the rubber or elastomer will cause the premature polymerization of an alkyl cyanoacrylate adhesive formulation. 

Apolymerfi e, AmberliteIRA900)-supportedreagent,f (W/ ) f (K=0-2), where P is the cationic part of the anion-exchange resin, acts as a source of nucleophilic fluorine and yet exhibits linuted basic character, thereby reducing the... 

Replacement of iodine in (perfluoroalkyl)ethyl iodides predominates over the usual conversion to olefins when the reagent is very nucleophilic and weakly basic Soft nucleophiles like sodium thiocyanate and sodium thiolates react well in displacements [46, 47] (equation 42)... 

The connection between basicity and nucleophilicity holds when compaiing atoms in the same row of the periodic table. Thus, HO is more basic and more nucleophilic than F , and H3N is more basic and more nucleophilic than H2O. It does not hold when proceeding down a column in the periodic table. For exanple, I is the least basic of the halide ions but is the most nucleophilic. F is the most basic halide ion but the least nucleophilic. 

Both the Edwards equation and Pearson s HSAB concept take as primary determinants of nucleophilicity the polarizability and basicity. A two-term equation of Bartoli and Todesco" uses these ideas also, but as a measure of polarizability the... 

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