Nitrogen Bronsted bases

Most of the imprinted sorbents used in MISPE were prepared using MAA and ethylene glycol dimethacrylate (EDMA) as monomers. In these cases elution of more weakly bound analytes such as triazines [19,30,32], 7-hydroxy-coumarin (2) [26] or theophylline (12) [28] can be achieved using methanol or water as elution solvent. For more strongly bound analytes such as stronger nitrogen Bronsted bases, efficient elution has been achieved using eluents of the same base solvent but with the addition of small amounts of acids (e.g. acetic acid, trifluoroacetic acid (TEA)) or base (e.g. triethylamine (TEA)) [20-22,25,33]. 

Aprotic protophillic solvents all nitrogen bases without protons, e.g., pyridine, and other conjugated amines, and fully alkylated amines or amides. The solvents function as Bronsted bases as well as Lewis bases and may have high permittivity. 

Caffeine and theophylline have pharmaceutically important chemical properties. Both arc weak BrOnsted bases. The reported pK values are 0.8 and 0.6 fur caffeine and 0.7 for theophylline. These values represent the basicity of the imino nitrogen at position 9. As acids, caffeine has a pK., above 14. and theophylline, a pK., of 8.8. In theophylline, a proton can be donated from position 7 (i.e.. it can act as a Bronsted acid). Caffeine cannoi donate a proton from position 7 and does not act as a Bretnsted acid at pH values under 14. Caffeine docs have electrophilic sites at positions I. 3. and 7. In addition to its Bronsted acid site at 7. theophylline has electrophilic sites at I and 3. In condensed terms, both compounds arc electron-pair donors, but only theophylline is a proton donor in most pharmaceutical system.s. 

Table 16.5 lists a number of common weak bases and their ionization constants. Note that the basicity of all these compounds is attributable to the lone pair of electrons on the nitrogen atom. The ability of the lone pair to accept a ion makes these substances Bronsted bases. 

Whenever any metal salt and any Bronsted base (an anion or other molecule with electronegative atoms, such as nitrogen or oxygen, that has the capacity to donate electrons) come into contact, coordination is likely to occur to give a complex compound. For example, when solid nickel chloride (yellow) reacts with a stream of ammonia gas, it is converted to purple hexamminenickel(II) chloride ... 

PROBLEM 13.51 Pyridine and imidazole are modest Bronsted bases at nitrogen, whereas pyrrole is not. 

Acyl compounds and nitriles are Bronsted bases and Lewis bases as well, with the carbonyl oxygen or the nitrile nitrogen being the center of basicity (Fig. 18.16). 

Amines are organic bases whose acid—base chemistry is like that of ammonia. For example, methyl-amine behaves as a Bronsted base because the nonbonded electron pair of the nitrogen atom can accept a proton from an acid such as hydronium ion. When methylamine accepts a proton, the conjugate acid, methyl-ammonium ion, is produced. 

Chiral Bronsted base catalysis began with the recognition of a natural product class of compounds in the cinchona alkaloid family [2]. Cinchona alkaloids are templates for Bronsted bases when their quinuclidine nitrogen is protonated by nucleophilic substrates, resulting in a stabihzed chiral intermediate for stereochemical attack of an electrophile. Systematic evaluation of structural variants to the scaffold... 

Michael donors and acceptors are common components in Bronsted base-mediated catalysis. Such transformations offer an uncomplicated route towards all-carbon quaternary stereocenters. In the most basic form, a, 5-unsaturated aldehydes are highly reactive templates towards nucleophilic reactions. Under such conditions, mechanistic studies show no polymerization of the unsaturated aldehydes under cinchona alkaloid catalysis [10]. This absence of polymerization is a key mechanistic indicator that the quinucUdine nitrogen of the catalyst does not act as a nucleophilic promoter. Rather, the quinucUdine nitrogen acts, as predicted, in a Bronsted basic deprotonation-activation of various cycUc and acyclic... 

Table 8.3 lists the base dissociation constants for several weak bases at 25°C. Nitrogen-containing compounds are Bronsted-Lowry bases, because the lone pair of electrons on a nitrogen atom can bond with H+ from water. The steps for solving problems that involve weak bases are similar to the steps you learned for solving problems that involve weak acids. 

Nucleophilicity. A distinction is usually made between nucleophilicity and Lowry-Bronsted basicity [213]. The latter involves specifically reaction at a proton which is complexed to a Lewis base (usually H2O), while the former refers to reactivity at centers other than H. Linear correlations have been shown for gas-phase basicity (proton affinity) and nucleophilicity of nitrogen bases toward CH3I in solution [214] where the solvent is not strongly involved in charge dispersal. In each case, reaction of the base/nucleophile... 

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