Acidity and Basicity of Amines

Let us see whether the remainder of the spectral data supports our tentative assignment. The C NMR spectrum, indeed, exhibits the expected six lines with the appropriate chemical shifts (Table 10-6, Section 21-3). 

What approximate spectral data (IR, NMR, mjz) would you expect for A-ethyl-2,2-dimethylpropanamine, shown in the margin  

Like the alcohols (Section 8-3), amines are both basic and acidic. Because nitrogen is less electronegative than oxygen, the acidity of amines is about 20 orders of magnitude less than that of comparable alcohols. Conversely, the lone pair is much more available for protonation, thereby causing amines to be better bases. 

We have seen evidence that amines are much less acidic than alcohols Amide ions, R2N , are used to deprotonate alcohols (Section 9-1). The equilibrium of this proton transfer lies strongly to the side of the alkoxide ion. The high value of the equilibrium constant, about 

is due to the strong basicity of amide ions, which is consistent with the low acidity of amines. The pA a of ammonia and alkanamines is of the order of 35. 

---

Steric interactions between bulky substituents such as t-Bu, leading to larger C-E-C bond angles, obviously affect the Lewis basicity caused by the increased -character of the electron lone pair. However, the strength of the Lewis acid-base interaction within an adduct as expressed by its dissociation enthalpy does not necessarily reflect the Lewis acidity and basicity of the pure fragments, because steric (repulsive) interactions between the substituents bound to both central elements may play a contradictory role. In particular, adducts containing small group 13/15 elements are very sensitive to such interactions as was shown for amine-borane and -alane adducts... 

Many phosphine-borane complexes Y3P BZ3 have been characterized. They include compouuds where Y = alkoxy, aUcyl, amino, halide, and hydride groups, and Z = alkyl, halide, and hydride. The stabilities of these complexes vary widely depending on the Lewis acidity and basicity of the boron and phosphorus moieties, respectively. The relative stabilities of Lewis acid-base complexes with BH3 are R3P > R3N > R3AS > R3Sb, but with BF3 the order is R3N > R3P > R3AS > RsSb. The stabihties of the borou halide complexes of phosphines follow the same order as the amine complexes BI3 > BBrs > BCI3 > BF3. 

As indicated, it is possible to preferentially stabilize the ion-pair side of the proton transfer potential by allowing the complex to interact with a polarizable medium. By incrementally raising the polarizability, one can manually fine-tune the relative stability of the ion pair relative to the neutral pair. This lowering of one end of the proton transfer potential relative to the other is very much akin to an adjustment of the acidity and basicity of the partners. When the systems described above were immersed in a dielectric continuum model of a polarizable medium, the equilibrium position of the proton did indeed shift toward the base. It was possible to raise p to the point where it became positive, indicating the complex had more ion pair character than neutral pair. Just as the sensitivity of p to the basicity of the amine increases in the order HF < HCl < HBr, so too does its sensitivity to the polarizability of the medium. Whereas complexes with HF show little displacement of the proton s equilibrium position as the polarizability of the medium increases, those in which HBr acts as the acid experience a rapid increase in p with more polarizable medium. This treatment was later confirmed at the correlated MP2 level in that the HjN- -HCl neutral pair is superceded in stability by the corresponding ion pair when immersed in a dielectric continuum. ... 

The halogen activity fits well the data on acidity and basicity of the arene (cyclopentadienyl) iron acids and amines. 

These reactions were studied in terms of steric effect, acidity and basicity of carboxylic acids, amines, and tertiary amines (e.g. pyridine) by using phosphorous acid and its mono-, di-, and tri-esters, as proposed in Scheme 1 for the case of the reaction with diesters. These N-phosphonium salts (i-4) were separated and characterized on the bases of the IR spectra, acid-base titration, and their reactions. 

N. C. J. Stutchbury and D. L. Cooper, J. Chem. Phys., 79, 4967 (1983). Charge Partitioning by Zero-Flux Surfaces Tbe Acidities and Basicities of Simple Aliphatic Alcohols and Amines. 

Acidity and basicity of ZnS have been studied by means of titrations using n-butyl amine and benzoic acid. According to the study, ZnS exhibited no basicity, but it contained a considerable amount of very weak acid sites. Upon heating at 570 — 770K, the acid amount increased to 1.1 or 2.5 mmole g for /fo 4.8, but acid sites stronger than 1.5 were not detected. Measurement of heat of adsorption of n-butylamine indicated the presence of 1.3 mmole g" of weak acidity on untreated ZnS. . ... 

Because of the analogy with ammonia, you should feel comfortable with the idea of amines as bases. The p/C value for a protonated amine, [RjNHjh is about 9, so it is a stronger acid than water, but not as strong as HjOh However, amines may also act as acids and can be deprotonated. For a typical secondary amine, the p/C is 36 (Equation 4.1). We will explore in more detail the acidity and basicity of all classes of compounds in Chapter 8. 

The basicities of amines, ethers, and carbonyl compounds are invariably decreased by fluonnation. 2,2,2-Tnfluoroethylamine (p f = 3.3 [61]) and C 5NH2 = -0.36 [62]) are about 10 times less basic than CH3CH2NH2 and CgH5NH2, respectively, and (CF3)2CHNH2 (p j, = 1 22 [71]) is over 10 times less basic than 1-C3H2NH2. The relative gas-phase acidities in Table 15 illustrate the large effect of fluonnation. Perfluoro-rerf-amines (R )3N and ethers R Rf have no basic character m solution [, 74], and CF3COCF3 is not protonated by superacids [72]. 

II This dual filling permits the absorption of both acid and basic vapours which may be evolved. Thus an amine hydrochloride, which has been recrystalliseu from concentrated hydrochloric acid, may be readily dried in such a desiccator. If concentrated sulphuric acid alone were used, so much hydrogen chloride would be liberated that the pressure inside the desiccator would rise considerably, and the rate of drying would be reduced. With sodium hydroxide present, however, the hydrogen chloride is removed, and the water is absorbed in the normal manner by the reagents but largely by the acid. 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

The strong electronegativity of the fluorinated substituents is reflected in the effect that this group has upon the acidity of alcohols and carboxylic acids, as well as the effect it has on the basicity of amines (Tables 1.3-1.5). 

However, these trends, which cannot provide an absolute scale for Lewis acidity and basicity, do not necessarily allow predictions of what kind of adducts will be formed.18 Gallane GaH3 for instance forms more stable adducts with phosphines than with amines. Consequently, reactions between H3Ga-<— NMe3 and tertiary phosphines PR3 yield the corresponding phosphine adducts. In sharp contrast, A1H3 forms significantly more stable adducts with amines than phosphines.19... 

Hydrogen bond donor solvents are simply those containing a hydrogen atom bound to an electronegative atom. These are often referred to as protic solvents, and the class includes water, carboxylic acids, alcohols and amines. For chemical reactions that involve the use of easily hydrolysed or solvolysed compounds, such as AICI3, it is important to avoid protic solvents. Hydrogen bond acceptors are solvents that have a lone pair available for donation, and include acetonitrile, pyridine and acetone. Kamlet-Taft a and ft parameters are solvatochromic measurements of the HBD and HBA properties of solvents, i.e. acidity and basicity, respectively [24], These measurements use the solvatochromic probe molecules V, V-die lliy I -4-n i in tan iline, which acts as a HBA, and 4-nitroaniline, which is a HBA and a HBD (Figure 1.17). 

---