Resonance stabilization amines

This resonance stabilization is lost when the amine group becomes protonated and o-cyanoaniline is therefore a weaker base than aniline... 

Alkylation of pyrimidin-2(or 4)-amine on a ring-nitrogen gives an imine, e.g. (8), of quite high basic strength (pjSTa 10.7) because its cation, e.g. (13 R = Me), has typical and effective resonance stabilization indeed, methylation of pyrimidine-2,4-diamine gives a still stronger base (pjSTa> 13) due to an even more resonance-stabilized cation (14). 

Hydrolysis of an enamine yields a carbonyl compound and a secondary amine. Only a few rate constants are mentioned in the literature. The rate of hydrolysis of l-(jS-styryl)piperidine and l-(l-hexenyl)piperidine have been determined in 95% ethanol at 20°C 13). The values for the first-order rate constants are 4 x 10 sec and approximately 10 sec , respectively. Apart from steric effects the difference in rate may be interpreted in terms of resonance stabilization by the phenyl group on the vinyl amine structure, thus lowering the nucleophilic reactivity of the /3-carbon atom of that enamine. 

Aliphatic amines undergo a characteristic a cleavage in the mass spectrometer, similar to that observed for alcohols. A C-C bond nearest the nitrogen atom is broken, yielding an alkyl radical and a resonance-stabilized, nitrogen-containing cation. 

In contrast with amines, amides (RCONH ) are nonbasic. Amides don t undergo substantial protonation by aqueous acids, and they are poor nucleophiles. The main reason for this difference in basicity between amines and amides is that an amide is stabilized by delocalization of the nitrogen lone-pair electrons through orbital overlap with the carbonyl group. In resonance terms, amides are more stable and less reactive than amines because they are hybrids of two resonance forms. This amide resonance stabilization is lost when the nitrogen atom is protonated, so protonation is disfavored. Electrostatic potential maps show clearly the decreased electron density on the amide nitrogen. 

Figure 24.3 Arylamines have a larger positive AG for protonation and are therefore less basic than alkylarnines, primarily because of resonance stabilization of the ground state. Electrostatic potential maps show that lone-pair electron density is delocalized in the amine but the charge is localized in the corresponding ammonium ion.

The products from benzotriazole, aldehydes and primary or secondary amines exist in the melt or in solution as equilibrium mixtures of 1- and 2-benzotriazolyl compounds, 99 and 100, whereas the solids are 1-benzotriazoles 99115. The equilibrium involves the resonance-stabilized aminomethyl cation and the delocalized benzotriazolide anion it accounts for the ease with which the bond attached to the benzotriazole moiety is cleaved. 

For Ar reactions with amines, the presence of a nitro group in a position ortho to the nucleofuge plays an important role. In spite of the steric effects which will tend to decrease the reactivity of o-nitroaromatics, and the fact that the rate-enhancing effect of the resonance stabilization of the transition state will be more important from the para position, a k°/kp ratio greater than unity is usually found in the reactions of nitroaromatics... 

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. 

Whereas the pATa for the a-protons of aldehydes and ketones is in the region 17-19, for esters such as ethyl acetate it is about 25. This difference must relate to the presence of the second oxygen in the ester, since resonance stabilization in the enolate anion should be the same. To explain this difference, overlap of the non-carbonyl oxygen lone pair is invoked. Because this introduces charge separation, it is a form of resonance stabilization that can occur only in the neutral ester, not in the enolate anion. It thus stabilizes the neutral ester, reduces carbonyl character, and there is less tendency to lose a proton from the a-carbon to produce the enolate. Note that this is not a new concept we used the same reasoning to explain why amides were not basic like amines (see Section 4.5.4). 

Like amides, 2- and 4-pyridones are also very weak bases, mnch weaker than amines. Like amides, they actnally protonate on oxygen rather than nitrogen (see Section 4.5.4). This fnrther emphasizes that the nitrogen lone pair is already in nse and not available for protonation. On the other hand, the N-H can readily be deprotonated pyridones are appreciably acidic abont 11). The conjngate base benefits from considerable resonance stabilization, both via... 

Chloroquinine is more basic than quinine, and the pATa suggests we must be looking at an aliphatic amine. There are two so which Note though that one of the amine functions is para to the quinoline nitrogen, so we may expect resonance stabilization when the quinoline nitrogen is protonated. 

Compcired to the aliphatic amines, the aromatic amines have lower values. This lower value indicates that the product of the protonation of aromatic amines is less stable. The decrease in stability is due to a loss in resonance stabilization of the protonated form. 

The lone pair of electrons on the nitrogen atom makes the amines Lewis bases. As Lewis bases, they may behave as nucleophiles. Because aromatic amines are resonance stabilized, they re weaker nucleophiles than alkyl amines. 

Amines react with nitrous acid (formed by the reaction NaN02 + H HNO2) to give a variety of products. The nitrous acid isn t very stable, so generating it in place from sodium nitrite is necessary. (Sodium nitrite is a meat preservative and a color enhancer.) Under acidic conditions, nitrous acid dehydrates to produce the nitrosonium ion, NO. The NO ion is a weak electrophile that s resonance stabilized. (See Chapter 7.) Figure 13-22 illustrates the dehydration of nitrous acid. 

As seen in Figure 13-24, secondary amines react directly with acidic sodium nitrite to form a nitrosamine. (These compounds are very, very toxic.) Primary amines react under similar conditions to form unstable diazonium salts (see Figure 13-25). Diazonium salts readily lose the very stable N2 to form reactive carbocations that are useful in a number of synthetic pathways. Figure 13-26 shows the resonance stabilization of a diazonium ion. 

Stork enamine synthesis takes advantage of the fact that an aldehyde or ketone reacts with a secondciry cimine to produce an enamine. Enamines cire resonance stabilized (see Figure 15-25) and have multiple applications. In the first resonance structure, the nitrogen is the nucleophile, while in the second resonance structure, the Ccirbanion is the nucleophile. Some commonly used secondary amines, pyrrolidine, piperidine, and morpholine, are shown in Figure 15-26. 

Basicity of aniline Aniline, like all other amines, is a basic compound ( Tb = 4.2 X 10 °). Anilinium ion has a = 4.63, whereas methylammo-nium ion has a pK = 10.66. Arylamines, e.g. aniline, are less basic than alkylamines, because the nitrogen lone pair electrons are delocalized by interaction with the aromatic ring tt electron system and are less available for bonding to H+. Arylamines are stabilized relative to alkylamines because of the five resonance structures as shown below. Resonance stabilization is lost on protonation, because only two resonance structures are possible for the arylammonium ion. 

A troublesome aspect still to be considered is the observation that salicylanil undergoes amine exchange, though 4-phenyliminopentane-2-one does not. Probably, this is due to the difference in resonance stabilization of the two compounds... 

When R and/or R1 = H, an M - 1 peak is usually visible. This is the same type of cleavage noted above for alcohols. The effect is more pronounced in amines because of the better resonance stabilization of the ion fragment by the less electronegative N atom compared with the O atom. 

Decreasing resonance stabilization of intermediates by altering the position of amine or replacing electron-conducting intercyclic linkages... 

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