Base Strengths of Amines

The base strength of an amine can be defined using the following equations  

In the same way as for because the concentration of water, [H2O], is large and changes very little it is incorporated into the value of the equilibrium constant which is re-named as K, . 

The larger the value of the stronger the base. The smaller the value of pXb the stronger the base, because. b = logio b (see Table 7.3.2) (see similar logic for the meaning of pH, Unit 5.5). 

Overlap between non-bonded electrons on N and the benzene electron cloud makes phenylamine a weaker base than methylamine 

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W Williams, GT Young. Amino acids and peptides. XXXV. Effect of solvent on the rates of racemization and coupling of acylamino acid p-nitrophenyl esters. Base strengths of amines in organic solvents, and related investigations. J Chem Soc Perkin Trans 1 1194, 1972. 

Conversely, fluorine or fluorocarbon groups have a major effect in reducing the base strength of amines, ethers and carbonyl compounds for example, 2,2,2-trifluoroethylamine (pKb = 3.3) is ca. 10 times less basic than ethylamine. Also, pentafluoropyridine is only protonated in strong acid [6], whereas hexafluoroacetone is not protonated even in superacids [7-9] and perfluorinated tertiary amines and ethers are sufficiently non-basic for them to be used as inert fluids interchangeably with perfluorocarbons. 

Base Strength of Amines As Measured by Their Basicity Constants and the Dissociation Constants of Their Conjugate Acids ... 

R. R. Grinstead, Base strength of amines in liquid-liquid extraction systems. Proceedings of Solv. Extr. Chem. Int. Conf, 1966, pp. 425—432. 

A convenient way to compare the base strengths of amines is to compare the pA values of their conjugate acids, the corresponding alkylaminium ions (Sections 3.6C and 20.3D). 

Based on inductive effects and steric effects, it is possible to categorize the base strength of amines in a general sense. The trend is NHg < RgN < RNH2 < RgNH, where secondary amines are the strongest bases and ammonia is the weakest base. Steric hindrance can play a subtler role in many amines, so this trend must be viewed as general, not absolute. 

It must be admitted that this traditional discussion of base strength of amines in terms of the pAT of the related ammonium ion is indirect. There is another, less common but undeniably more direct method. That is to frame the discussion in terms of the p. b ( log where ATb is the basicity constant of the amine (Fig. 6.47). 

Recently Stamhuis et al. (33) have determined the base strengths of morpholine, piperidine, and pyrrolidine enamines of isobutyraldehyde in aqueous solutions by kinetic, potentiometric, and spectroscopic methods at 25° and found that these enamines are 200-1000 times weaker bases than the secondary amines from which they are formed and 30-200 times less basic than the corresponding saturated tertiary enamines. The baseweakening effect has been attributed to the electron-withdrawing inductive effect of the double bond and the overlap of the electron pair on the nitrogen atom with the tt electrons of the double bond. It was pointed out that the kinetic protonation in the hydrolysis of these enamines occurs at the nitrogen atom, whereas the protonation under thermodynamic control takes place at the -carbon atom, which is, however, dependent upon the pH of the solution (84,85). The measurement of base strengths of enamines in chloroform solution show that they are 10-30 times weaker bases than the secondary amines from which they are derived (4,86). 

Since OCH3 is electron-donating through extended n bonding, it increases electron density on N and the base strength of the amine because the ring accepts less electron density from N. 

A straightforward treatment of the base strength of aniline can be given. A saturated aliphatic amine such as methylamine has a base constant Kb of about 5 X 10 4, corresponding to the reaction H H... 

The base strengths of simple alkanamines usually are around Kb = 10-4 (Ka = 10-10) in water solution, and vary within perhaps a factor of 10 from ammonia to primary, secondary, and tertiary amines, as can be seen from the data in Table 23-1. Cyclohexanamine has about the same base strength as methanamine, whereas the effect on the basic nitrogen of being in a saturated ring, as in azacyclohexane, increases the base strength somewhat. 

Exercise 23-11 Draw atomic-orbital models for benzenamine and its conjugate acid and describe the features of these models that account for the low base strength of benzenamine relative to saturated amines. 

The base One equivalent, at least, of a base relative to the aryl halide must be present to achieve the alkene substitution catalytically. Most often a tertiary amine is employed. Secondary amines also appear to be suitable but primary amines usually are not. The base strength of the amine is important since only quite basic amines such as triethylamine work well. Acetate salts, carbonates and bicarbonates also are suitable bases but solubility may cause difficulties in some instances. The addition of a phase transfer agent such as a quaternary ammonium salt has often solved this problem. The inorganic bases, of course, may cause other problems such as ester hydrolysis, aldol condensations and other undesired side reactions. 

Triflate, tosylate and mesylate are the anions of strong acids. The weak conjugate bases are poor nucleophiles. Nucleophilicity increases in parallel with the base strength. Thus, amines, alcohols and alkoxides are very good nucleophiles. Base strength is a rough measure of how reactive the nonbonding electron pair is thus, it is not necessary for a nucleophile to be anionic. 

Amines react with strong acids to form amine salts. The pKas of amine salts are related to the base strength of the corresponding amines. Alkylammonium salts have pKas of 9-10 while arylammonium salts have pKas of 4-5. The fact that these salts are usually water-soluble can be exploited in separating amines from neutral or acidic contaminants. Chiral amines can be used to resolve enantiomeric acids, through the formation of diastereomeric salts. 

Because they vary by many orders of magnitude, base-dissociation constants are usually listed as their negative logarithms, or pATb values. For example, if a certain amine has Kb = 10-3, then pKb = 3. Just as we used pKa values to indicate acid strengths (stronger acids have smaller pKa values), we use pKb values to compare the relative strengths of amines as proton bases. 

What happens to the same reaction in aqueous solution Whereas the neutral reactants, ammonia and trimethylamine, are hydrated about equally well, the ammonium ion is hydrated much more strongly than is MejNH . As shown by Eqs. (4-21) and (4-22), solvation through hydrogen bonding will tend to increase the base strength of all amines... 

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