Electrophilic aromatic substitution nitrogen

The orbital and resonance models for bonding in arylamines are simply alternative ways of describing the same phenomenon Delocalization of the nitrogen lone pair decreases the electron density at nitrogen while increasing it m the rr system of the aro matic ring We ve already seen one chemical consequence of this m the high level of reactivity of aniline m electrophilic aromatic substitution reactions (Section 12 12) Other ways m which electron delocalization affects the properties of arylamines are described m later sections of this chapter... 

Arylamines contain two functional groups the amine group and the aromatic ring they are difunctional compounds The reactivity of the amine group is affected by its aryl substituent and the reactivity of the ring is affected by its amine substituent The same electron delocalization that reduces the basicity and the nucleophilicity of an arylamme nitrogen increases the electron density in the aromatic ring and makes arylamines extremely reactive toward electrophilic aromatic substitution... 

The y-nitrogen atom of a sulfonic acid azide is electrophilic and reacts in an electrophilic aromatic substitution with an activated benzene or naphthalene derivative, e.g., a phenoxide ion, forming a l-tosyl-3-aryltriazene (2.47). The 1,4-quinone diazide is obtained by hydrolysis (Scheme 2-30, Tedder and Webster, 1960). The general applicability of this reaction seems to be doubtful. With 1-naphthol the 1,2-naphthoquinone diazide was obtained, not the 1,4-isomer. 

The reaction of 151 with methanol to give dimethyl phosphate (154) or with N-methylaniline to form the phosphoramidate 155 and (presumably) the pyrophosphate 156 complies with expectations. The formation of dimethyl phosphate does not constitute, however, reliable evidence for the formation of intermediate 151 since methanol can also react with polymeric metaphosphates to give dimethyl phosphate. On the other hand, reaction of polyphosphates with N-methylaniline to give 156 can be ruled out (control experiments). The formation of 156 might encourage speculations whether the reaction with N,N-diethylaniline might involve initial preferential reaction of monomeric methyl metaphosphate via interaction with the nitrogen lone pair to form a phosphoric ester amide which is cleaved to phosphates or pyrophosphates on subsequent work-up (water, methanol). Such a reaction route would at least explain the low extent of electrophilic aromatic substitution by methyl metaphosphate. 

Individual substitutions may not necessarily be true electrophilic aromatic substitution reactions. Usually it is assumed that they are, however, and with this assumption the furan nucleus can be compared with others. For tri-fluoroacetylation by trifluoroacetic anhydride at 75 C relative rates have been established, by means of competition experiments 149 thiophene, 1 selenophene, 6.5 furan, 1.4 x 102 2-methylfuran, 1.2 x 105 pyrrole, 5.3 x 107. While nitrogen is usually a better source of electrons for an incoming electrophile (as in pyrrole versus furan) there are exceptions. For example, the enamine 63 reacts with Eschenmoser s salt at the 5-position and not at the enamine grouping.150 Also amusing is an attempted Fischer indole synthesis in which a furan ring is near the reaction site and diverted the reaction into a pyrazole synthesis.151... 

Electron-transfer activation of electrophilic aromatic substitution 274 Electron-transfer activation in nitrogen dioxide reactivity toward organic donors 292... 

Electrophilic addition reactions. See also Addition reactions with butylenes, 4 405-408 of maleic anhydride, 75 490 with methacrylic acid/derivatives, 76 236-237 of propylene, 20 774 Electrophilic aromatic substitution, benzene, 3 599-601 Electrophilic attack, at nitrogen and carbon, 27 98... 

Electrophilic substitutions Pyridine s electron-withdrawing nitrogen causes the ring carbons to have significantly less electron density than the ring carbons of benzene. Thus, pyridine is less reactive than benzene towards electrophilic aromatic substitution. However, pyridine undergoes some electrophilic substitution reactions under drastic conditions, e.g. high temperature, and the yields of these reactions are usually quite low. The main substitution takes place at C-3. 

Electrophilic aromatic substitutions The chemistry of pyrimidine is similar to that of pyridine with the notable exception that the second nitrogen in the aromatic ring makes it less reactive towards electrophilic substitutions. For example, nitration can only be carried out when there are two ring-activating substituents present on the pyrimidine ring (e.g. 2,4-dihydroxypyrimidine or uracil). The most activated position towards electrophilic substitution is C-5. 

The ring that bears the nitrogen in benzanilide is activated toward electrophilic aromatic substitution. The ring that bears the C=0 is strongly deactivated. 

Attack at C-3 gives a carbocation that is resonance-stabilized by a nonbonded pair of electrons on the adjacent nitrogen. Attack at C-2 gives a cation in which the positive charge is not adjacent to an atom bearing nonbonded electrons. Any additional resonance contributors disrupt the benzenoid structure in the left ring. Therefore, electrophilic aromatic substitution reactions of indole occur primarily at C-3. 

Scheme 1. Palladacycle formation through a sequence of oxidative addition, insertion, and electrophilic aromatic substitution. L= phosphorous or nitrogen ligands, solvent, or coordinating species.

Pyrimidine forms 4-bromopyrimidine when the hydrochloride is heated with bromine at 160°C (or at 130°C in nitrobenzene) (73JHC153), the process being preceded by a vigorous reaction at lower temperature (57CB1837 58AG571). It is likely that N-bromo compounds and perbro-mides are implicated in these reactions, which occur (3 to the ring nitrogens, and they are not conventional electrophilic aromatic substitutions. 

We have already described how nitration leads eventually to aromatic amines by reduction of the nitro group. In the next chapter you will meet the further development of these amines into diazoni-um salts as reagents for nucleophilic aromatic substitution by the S l mechanism with loss of nitrogen. In this chapter we need to address their potential for electrophilic aromatic substitution without the loss of nitrogen as this leads to the important azo dyes. Treatment of the amine with nitrous acid (H0N=0) at around 0°C gives the diazonium salt. 

The other simple five-membered heterocycles are furan, with an oxygen atom instead of nitro- pyrrole gen, and thiophene with a sulfur atom. They also undergo electrophilic aromatic substitution very Ft ft readily, though not so readily as pyrrole. Nitrogen is the most powerful electron donor of the three, 1 J> oxygen the next, and sulfur the least. Thiophene is very similar to benzene in reactivity. N... 

The aromatic ring is deactivated toward electrophilic aromatic substitution by the combined electron-withdrawing inductive effect of electronegative nitrogen and oxygen. The lone pair of electrons of nitrogen can, however, stabilize by resonance the ortho and para substituted intermediates but not the meta intermediate. 

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