Heteroaromatic amines basicity

This scheme eliminates the process of converting bis(etherimide)s to bis(ether anhydride)s. When polyetherimides are fusible the polymerization is performed in the melt, allowing the monamine to distill off. It is advantageous if the amino groups of diamines are more basic or nucleophilic than the by-product monoamine. Bisimides derived from heteroaromatic amines such as 2-arninopyridine are readily exchanged by common aromatic diamines (68,69). High molecular weight polyetherimides have been synthesized from various N,lSf -bis(heteroaryl)bis(etherimide)s. 

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. 

Aromatic and heteroaromatic amines can be linked to insoluble supports using strategies similar to those used for aliphatic amines. Because of the lower basicities of aromatic amines, however, their /V-bcnzyl derivatives will usually be more susceptible to acidolytic cleavage than aliphatic /V-bcnzylamincs. For the same reason, N-acyl derivatives of aromatic amines will generally be more sensitive towards nucleophiles than the corresponding derivatives of aliphatic amines. 

The bulk of this Appendix is on acidity because many more functional groups are acidic than are basic. Basically (oooh, sony), only one functional group is basic amines. There is variation among aliphatic, aromatic, and heteroaromatic amines these are covered thoroughly in text sections 19-5 and 19-6. One point in the text. Just before Table 19-3, deserves emphasis for any conjugate acid-base pair ... 

High trimerization rates have also been observed in the presence of basic catalysts. Aliphatic and heteroaromatic amines, alkali hydroxides and alkali alkoxides have been used.247 249,256 The base presumably adds to the carbon atom of the cyanate group, and then the adduct takes part in the trimerization reaction.257 Pyridines and derivatives are superior in catalytic activity compared to tertiary alkylamines. 

Basic Red 22 (134), which contains 1 part ia 7 of the yellowish red 1,4-dimethyl isomer, Basic Red 29 (135), and Basic Yellow 25 (136) are all examples of delocalized cationic azo dyes. Dyes of this type can also be synthesized by Hbnig s oxidative coupling reaction of heteroaromatic hydrazones with tertiary aromatic amines. 

Autocatalysis may arise when the nucleophilic atom of the reagent is bound to a hydrogen atom which is eventually eliminated during the reaction. This occurs with neutral reagents such as primary or secondary amines, thiols, and alcohols. If the displaced group (usually an anion) is a sufficiently weak base, the proton is effectively transferred to any basic reactant. Hence, the best known examples of autocatalysis involve chloro-A-heteroaromatic compounds as the substrates. 

We mention Williams work briefly here because it may also explain Blangey s observations strongly basic primary amines unequivocally form 7V-nitrosoanilinium ions in strongly acidic media. In contrast to the rate-limiting deprotonations of the less basic aromatic and heteroaromatic nitrosoamine cations discussed in this section, the TV-nitroso cation of a strongly basic amine deprotonates extremely slowly. Therefore, the nitroso rearrangement, the Fischer-Hepp reaction, competes effectively with the 7V-deprotonation. 

Compounds with a high HOMO and LUMO (Figure 5.5c) tend to be stable to selfreaction but are chemically reactive as Lewis bases and nucleophiles. The higher the HOMO, the more reactive. Carbanions, with HOMO near a, are the most powerful bases and nucleophiles, followed by amides and alkoxides. The neutral nitrogen (amines, heteroaromatics) and oxygen bases (water, alcohols, ethers, and carbonyls) will only react with relatively strong Lewis acids. Extensive tabulations of gas-phase basicities or proton affinities (i.e., —AG° of protonation) exist [109, 110]. These will be discussed in subsequent chapters. 

Monobasic derivatives do not yield potent antiviral agents, nor do they induce interferon when compared to the corresponding bis basic derivatives. Removal of the amine terminus results in loss of antiviral activity. Maximum activity is observed with no less than 3-rings in the central aromatic or heteroaromatic nucleus. 

In the reaction of 1/7-indol-l-ylsilylamine 256 and lithium amide the latter acts as the lithiation reagent for the more basic nitrogen atom of the heteroaromatic system. The products are 1-lithium indolide and amine 253 (R = Bu"). For this reason a reverse synthetic strategy is necessary to obtain compound 256 (Scheme 53) <1996JOM(524)203>. 

The foimation of aromatic diazonium salts from aromatic primary amines is one of the oldest synthetic procedures in organic chemistry. Methods based on nitrosation of amine with nitrous acid in aqueous solution are die best known, but diere are variants which are of particular use widi weakly basic amines and for the isolation of diazonium salts fiom nonaqueous media. General reviews include a book by Saunders and AUen and a survey of preparative methods by Schank. There ate also reviews on the diazotization of heteroaromatic primary amines and on the diazotization of weakly basic amines in strongly acidic media. The diazotization process (Scheme 11) goes by way of a primary nitrosamine. 

The pyrrolic nitrogen (a), in which the lone pair is involved in the imidazole heteroaromatic system, is non-basic. The middle nitrogen (b) is the imide nitrogen in which the lone pair is in an sp- hydrbridized orbital. The side-chain amine (c) is the most basic. 

This procedure has found wdde application in the synthesis of aromatic and heteroaromatic azides the yields are usually high and often quantitative. General procedures have been developed by Smith and co-workers the method of choice mainly being determined by the basicity of the amine involved or the solubility of its salts. Weakly basic amines, for example, are diazotized with amyl nitrite in an acetic acid-concentrated sulphuric acid mixture and aqueous sodium azide is subsequently added. Amines which form insoluble salts with common mineral acids zu e converted to the more soluble 2-hydroxyethanesulphonic acid salts prior to diazotization. This procedure has been applied in the diazotization of the N-(aminophenyl)phthalimides (254). Treatment of the resulting diazonium compounds (255) with hydrazoic acid and removal of the protecting phthalimido group affords the otherwise inaccessible azidoanilines (equation 134). Some representative examples of azides recently synthesized by these methods, are shown in Table 11. 

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