Protons on Nitrogen Amines

Under these conditions, the predominant species in solution is the protonated amine, and intermole-cular proton exchange is slowed, often allowing us to observe spin-spin coupling interactions that are decoupled and masked by exchange in the free amine. 

In amides, which are less basic than amines, proton exchange is slow, and coupling is often observed between the protons on nitrogen and those on the a carbon of an alkyl substituent that is substituted on the same nitrogen. 

The spectra of n-butylamine (Fig. 6.7) and 1-phenylethylamine (Fig. 6.8) are examples of uncomplicated spectra (no NH—CH splitting). Unfortunately, the spectra of amines are not always this simple. Another factor can complicate the sphtting patterns of both amines and amides nitrogen itself has a nuclear spin, which is unity (7 = 1). Nitrogen can therefore adopt spin states -f-1, 0, and -1. On the 

Geminal couphng Vicinal couphng V and V negligible (i.e., almost always zero) 

The 3 methyl protons split each peak into a quartet 

342 Nuclear Magnetic Resonance Spectroscopy Part Four 

Copyright 2013 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. 

Unfortunately, the spectra of amines are not always this simple. Another factor can complicate the splitting patterns of both amines and amides Nitrogen itself has a nuclear spin, which is unity (/ = 1). 

Nitrogen can therefore adopt three spin states +1,0, and -1. On the basis of what we know so far of spin-spin couphng, we can predict the following possible types of interaction between H and N  

---

The amine must be primary (RNH2) or secondary (R2NH) Tertiary amines (R3N) can not form amides because they have no proton on nitrogen that can be replaced by an acyl group... 

Reaction of an aldehyde or ketone with a secondary amine, R2NH, rather than a primary amine yields an enamine. The process is identical to imine formation up to the iminium ion stage, but at this point there is no proton on nitrogen that can be lost to form a neutral imine product. Instead, a proton is lost from the neighboring carbon (the a carbon), yielding an enamine (Figure 19.10). 

Pre-eminent amongst examples is the case of amides, which do not show the typical basicity of amines. Acetamide, for example, has pATa — 1.4, compared with a 10.7 in the case of ethylamine. This reluctance to protonate on nitrogen is caused by delocalization in the neutral amide, in which the nitrogen lone pair is able to overlap into the n system. This type of resonance stabilization would not be possible with nitrogen protonated, since the lone pair is already involved in the protonation process. Indeed, if amides do act as bases, then protonation occurs on oxygen, not on nitrogen. Resonance stabilization is still possible in the D-protonated amide, whereas it is not possible in the A-protonated amide. Note that resonance stabilization makes the D-protonated amide somewhat less acidic than the hydronium ion (pATa — 1.7) the amide oxygen is more basic than water. 

Amides may be hydrolysed to carboxylic acids by either acids or bases, though hydrolysis is considerably slower than with esters. Although amines are bases and become protonated on nitrogen via the lone pair electrons, we know that amides are not basic (see Section 4.5.4). This is because the lone pair on the nitrogen in amides is able to overlap into the carbonyl... 

We also recognized that compound 5 possessed a very acidic proton on the amine nitrogen and that many known compounds that exhibit odor and taste contain acidic SH, OH, or NH protons. We thought it desirable to replace the proton on the amine with an... 

The use of trifluoroacetic acid as both a protonat-ing agent and a solvent frequently allows classification of amines as primary, secondary, or tertiary. This is illustrated in Table 3.4 in which the number of protons on nitrogen determines the multiplicity of the methylene... 

Nitrogen is not as electronegative as oxygen and the halogens, so the protons on the a carbon atoms of amines are not as strongly deshielded. Protons on an amine s a carbon atom generally absorb between 8 2 and 8 3, but the exact position depends on the structure and substitution of the amine. 

An enamine results from the reaction of a ketone or aldehyde with a secondary amine. Recall that a ketone or aldehyde reacts with a primary amine (Section 18-15) to form a carbinolamine, which dehydrates to give the C=N double bond of an imine. But a carbinolamine from a secondary amine does not form a C=N double bond because there is no proton on nitrogen to eliminate. A proton is lost from the a carbon, forming the C=C double bond of an enamine. 

Af,Af-dimethylvinylamine derivatives with alkyl substituents at the carbon atoms should behave similarly to saturated amines, being protonated on nitrogen. The results of both monomethylation and dimethylation at the ft carbon are consistent which such a behaviour, as shown by the SAG° values below. Consequently, they should be protonated at the nitrogen atom. On the other hand, the a,/7-dimethyl derivative appears to be protonated at a different site, so it could be a carbon base. 

The neutral intermediate, 4-26, can be protonated on either oxygen or nitrogen, but only protonation on nitrogen leads to product formation. Notice that the NH2 group is now an amine and is much more basic than the NH2 group of the starting amide. 

Calculation of the heats of combustion for imidazoles suggest that, in substituent-nucleus tautomerism, the tautomer with the mobile proton on nitrogen should be more stable than that with it on carbon, and that the amino forms of amines, and the carbonyl forms of hydroxy compounds, are preferred. ... 

The reaction between all classes of amines (except tertiary) and either ketones or aldehydes is usually straightforward and generally leads to imines in the case of primary amines and to enamines with secondary amines, which bear only one labile proton on nitrogen (equation 4). 

The hydrolysis of simple imines occurs readily in aqueous acid, and has been studied in detail by kinetic methods. The precise mechanism is a function of the reactant structure and the pH of the solution. The overall mechanism consists of an addition of water to the C=N bond, followed by expulsion of the amine from a tetrahedral intermediate. There are at least four variants of the tetrahedral intermediate that differ in the extent and site of protonation. In the general mechanism below, the neutral intermediate is labeled TI° and the zwitterionic form is labeled. There are two possible monoprotonated forms, one protonated on oxygen (TI +) and one protonated on nitrogen (TI +). 

---