Heterocyclic aromatic amines, basicity

Imidazole and its derivatives form an interesting and important class of heterocyclic aromatic amines. Imidazole is approximately 100 times more basic than pyridine. 

Imidazole and its derivatives form an interesting and important class of heterocyclic aromatic amines. Imidazole is approximately 100 times more basic than pyridine. Protonation of imidazole yields an ion that is stabilized by the electron delocalization represented in the resonance structnres shown ... 

Malonyl dichloride and its disubstitution products react with strongly basic amines to give preferentially the diamides. Ring closure to cyclic imides occurs only between disubstituted malonyl dichlorides and weakly basic aromatic or heterocyclic-aromatic amines. 3,3-Disubstituted l-(disubstituted-amino)-2,4-azetidinediones are obtained analogously from iV,iV-disubstituted hydrazines.602... 

Morpholine (B) is the stronger base (pKb 5.79). It has a basicity comparable to that of secondary aliphatic amines. FVridine (A), a heterocyclic aromatic amine pl 8.75), is considerably less basic than aliphatic amines. Benzylamine (D), a primary aliphatic amine, is the stronger base (p/Cj, 3-4). o-Toluidine (C), an aromatic amine, is the weaker base (pKb 9-10). In the absence of Table 10.2, one can see that the electron pair on nitrogen in o-toluidine can participate in resonance with the benzene ring, while there are no resonance possibilities in benzylamine.This results in o-toluidine s electron pair being less available for reaction with an acid. 

We discussed fhe sfrucfure and bonding in pyridine and imidazole in Section 21.2D. In accounting for the relative basicities of fhese and other heterocyclic aromatic amines, it is important to determine first whether the unshared pair of electrons on nitrogen is a part of fhe An + 2) tt elecfrons giving rise to aromaticity. In the case of pyridine, fhe unshared pair of elecfrons is nof a part of the aromatic sextet. 

The basicity of N atoms within heterocyclic aromatic amines depends on whether the N lone pair is part of the aromatic v system. 

Basicity of Heterocyclic Aromatic Amines (Section 23.5C) Heterocyclic aromatic amines are considerably weaker bases than aliphatic amines. 

Because the imidazole group on the side chain of histidine contains six tt electrons in a planar, fully conjugated ring, imidazole is classified as a heterocyclic aromatic amine (Section 21.2D). The unshared pair of electrons on one nitrogen is a part of the aromatic sextet, whereas that on the other nitrogen is not. The pair of electrons that is not part of the aromatic sextet is responsible for the basic properties of the imidazole ring. Protonation of this nitrogen produces a resonance-stabilized cation. 

The nitrogen of aHphatic and aromatic amines is alkylated rapidly by alkyl sulfates yielding the usual mixtures. Most tertiary amines and nitrogen heterocycles are converted to quaternary ammonium salts, unless the nitrogen is of very low basicity, eg, ia tn phenylamine. The position of dimethyl sulfate-produced methylation of several heterocycles with more than one heteroatom has been examined (22). Acyl cyanamides can be methylated (23). Metal cyanates are converted to methyl isocyanate or ethyl isocyanate ia high yields by heating the mixtures (24,25). 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

They showed that use of the phosphonium IL resulted in milder conditions and yields comparable with conventional solvents. Both aliphatic and aromatic amines reacted well in presence of phosphonium ILs, in contrast with ammonium ILs where only aliphatic amines acted as Michael donors. Yang et al. demonstrated the use of aromatic amines and N-heterocycles as Michael donors in presence of a basic IL such as [emim]OH. They reacted cyclohexenone with aniline in presence of [emim]OH at room temperature to give the corresponding Michael adduct, Scheme 25. 

The basic ionic liquid [BmimJOH has been introduced as a catalyst for the aza-Michael addition of aromatic amines and A-heterocycles to cyclic or acyclic ketones under solvent-free conditions.138... 

Enamine Dyes are obtained by condensation of heterocyclic methylene- a) -aldehydes with aromatic amines in an acid medium. Technically important dyes contain 1,3,3-trimethyl-2-methyleneindoline-a)-aldehyde as aldehyde component [7], C.I. Basic Yellow 11, the condensation product formed with 2,4-dimethoxyan-iline, is of particular importance (see 3.8.4). This compound dyes polyacrylonitrile a lightfast, brilliant, greenish-yellow shade. 

Examples of aromatic amines that can be dia-zotized are shown in Fig. 13.83. This extremely abbreviated list is designed to show that a wide variety of amines can be used, including hydrophobic, weakly basic, hydrophilic, and heterocyclic compounds. orf/zo-Diamines are not typically used because of their propensity to undergo triazole formation (Fig. 13.84). 

The impetus for the development of synthesis and characterization of complexes of lanthanides with organic nitrogen donor ligands is due to the search for more efficient luminescent rare earth compounds. One of the difficulties is the risk of precipitating lanthanide hydroxides in the process of synthesis of lanthanide complexes with organic amines. In the early stages, lanthanide complexes of heterocyclic bases of low basicities were prepared in aqueous alcoholic media [224], In the synthesis section it was appropriately pointed out the need for the anhydrous conditions and involved procedures for the preparation of lanthanide complexes of ligands of non-ionizable nature. Some representative complexes of both aliphatic and aromatic amines are listed in Table 4.19. 

The six-membered nitrogen heterocycle pyridine (Figure 3.19) is also a weak base. In the case of pyridine, however, only one electron from the nitrogen contributes to the aromatic sextet. This leaves an unshared pair of electrons, which can accept a proton, so that pyridine is measurably basic with a pKa value of 5.2. This value is similar to that found in aromatic amines such as aniline (aminobenzene). 

It has long been observed that some aromatic nitrogen heterocyclic compounds aminate more easily than others. For instance, 1-methylbenzimidazole is aminated in a matter of a few minutes, whereas pyridine requires about 2 hr. In order to explain this, chemists in the U.S.S.R. have considered four factors they believe are most responsible for causing different rates of amination in aprotic solvents at elevated temperatures (heterogeneous conditions). They are (1) basicity of the heterocycle (2) positive charge on the carbon atom adjacent to the nitrogen (3) polarizability of the C=N bond and (4) ease of aromatization of the a-adduct (76CHE210). The first three pertain to the addition step of the Chichibabin reaction and the last factor depends upon the hydride-ion elimination step. 

The basic component is a primary or secondary aliphatic, cycloaliphatic or aromatic amine, an aliphatic, aromatic or heterocyclic hydroxy compound, or an oxime of aliphatic, cycloaliphatic or heterocyclic ketones. 

Most unsaturated ring quats of industrial importance are alkylpyridinium halides (I) and substituted imidazolinium compounds (11). To prepare alkylpyridinium halide, pyridine is reacted with the equimolar amounts of alkyl halide for several hours at 100-150 °C without solvent according the reactions given above. The reaction is two orders slower in this case because the basicity of pyridine is much weaker in comparison with aliphatic tertiary amines and heterocyclic aliphatic amines, such as N-alkylpiperidine and N-alkylmorpholine, too. Typical examples of the aromatic quaternaries are given below ... 

Oxidative amination of aromatic amines which are less basic than aliphatic amines proceeds smoothly without protection of amines. The intramolecular reaction of aniline derivatives offers good synthetic methods for heterocycles. 2-Methylindole is obtained by 5-exo amination of 2-allylaniline [50]. As an application, A-methyl-2-methyl-3-siloxyindole 114 was prepared from A-methyl-2-(l-siloxyallyl)aniline 113. Without silyl protection, no reaction occurred [51]. If there is another olefinic bond in the same molecule, the aminopalladation product 116 of the amide 115 undergoes olefin insertion to give the tricyclic compound 117 [50]. 2,2-Dimethyl-1,2-dihydroquinoline (119) was obtained by 6-endo cyclization of 2-(3,3-dimethylallyl)aniline (118). 

The question of the rate-determining step in the Chichibabin reaction is still open. Clearly, it is difficult to expect that such a complex process can be controlled by any single parameter. On the basis of the rate of hydrogen gas evolution, the following sequence of the reactivity of aza-heterocyclic compounds has been established 1-R-benzimidazoles > isoquinoline > 1-R-perimidines > benzo[/]quinoline > pyridine acridine. Evidently, this raw indicates that sodamide amination depends on number of factors, involving electron deficiency of the substrate C(a)-atom, ease of the adduct aromatization, substrate basicity, etc. Evidently, acridine s position in this raw reflects the difficulty of the y-amination. 

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