Electrophilic Attack on Nitrogen

Electrophilic attack on the nitrogen atom of aziridines and azirines results in either derivatization or a subsequent ring-opening reaction. Reactions involving nucleophilic attack at carbon promoted by protonation or Lewis acid complexation at nitrogen are covered in Section 1.01.6.3.2. 

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Acylations were often carried out with diaziridines. Twofold acylation is normally observed when two NH groups are present. Most acylations were performed with benzoyl chloride, acetyl chloride or phenyl isocyanate (B-67MI50800). Ring opening reactions during acylation, foreseeable for intermediates of electrophilic attack on nitrogen, were observed only seldom, provided mild conditions were used. 

In addition to those methods described in CHEC(1984) and CHEC-II(1996) (primarily alkylation and acylation reactions), Vicentini <1996T7179> has shown that 5-methylimidazo[4,5-f]pyrazole 28 can undergo electrophilic attack on nitrogen by hydroxylamine 0-sulfonic acid to yield the 4-amino species 29 (Equation 1). 

An intramolecular reaction, which could be viewed as an electrophilic attack on nitrogen, is mentioned under the reactions of the carbocyclic ring (see Section 7.21.6.1.3) <83CPB1518>. The dihydrobenzodipyrrole (45) was acylated on the pyrrolidine nitrogen atom (87CC1406). The oxidation of some benzodipyrroles, e.g. compound (6), and related tripyrroles, to their JV-oxides can be viewed as an electrophilic attack on nitrogen. 

A. Reactivity of Ring Atoms 1. Electrophilic Attack on Nitrogen... 

We conclude that W(Me)o and W(NMe2)e generally react via different mechanisms. W(Me)e reacts (28) via initial nucleophilic attack at tungsten whereas W(NMe2)e reacts via electrophilic attack on nitrogen nonbonding lone pairs. 

So far, all electrophilic attacks on nitrogen in this section have occurred at ring N-atoms with maintenance of the... 

Electrophiles attack on nitrogen in protonation, alkylation, and N-oxidation reactions. Electrophihc substitutions at carbon are not observed in the parent compound. Donor substituents (e.g., OH or NH2) increase the SsAr reactivity of the pyrimidine system (two substituents lead to an S Ar reactivity corresponding to benzene, three to that of phenol) and enable nitration, nitrosation, aminomethylation, and azo-coupHng to take place at the 5-position, for example ... 

Electrophilic Attack at Nitrogen. The lone pair on pyridiae (1) = 5.22) reacts with electrophiles under mild conditions, with protonic... 

Chloramines are formed by electrophilic attack on ammonia nitrogen via a series of bimolecular reactions, where k M ) and K (Af ) are the... 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

The pyrazole molecule resembles both pyridine (the N(2)—C(3) part) and pyrrole (the N(l)—C(5)—C(4) part) and its reactivity reflects also this duality of behaviour. The pyridinic N-2 atom is susceptible to electrophilic attack (Section 4.04.2.1.3) and the pyrrolic N-1 atom is unreactive, but the N-1 proton can be removed by nucleophiles. However, N-2 is less nucleophilic than the pyridine nitrogen atom and N(1)H more acidic than the corresponding pyrrolic NH group. Electrophilic attack on C-4 is generally preferred, contrary to pyrrole which reacts often on C-2 (a attack). When position 3 is unsubstituted, powerful nucleophiles can abstract the proton with a concomitant ring opening of the anion. 

In the preceding parts of Section 4.04.2.1.3 the electrophilic attack on pyrazolic nitrogen with the concomitant formation of different classes of N—R bond has been examined N—H (iv, v), N—metal (vi), N—C(sp ) (vii, viii, xi), N—C(sp ) (be, x, xi), N—SO2R (x), N—halogen (xii), N—O (xiii) and N—-N (xiv). In this last part the reaction with other Lewis acids leading to the formation of pyrazole N—metalloid bonds will be discussed, and the study of their reactivity will be dealt with in Section 4.04.2.3.lO(viii). 

Sodium and silver pyrazole salts (Section 4.04.2.1.3(vl)) are often used Instead of neutral pyrazoles to facilitate electrophilic attack on the ring nitrogen atoms. For example, pyrazolyl-methanes (234)-(236) have been prepared from pyrazole anions (Section 4.04.2.1.3(vlll)). Unstable 2-acetyllndazoles are obtained from the reactive silver salts of indazoles (Section 4.04.2.1.3 (x)). Electrophilic attack on the ring carbon atoms also occurs more readily in... 

Experimental evidence, obtained in protonation (3,6), acylation (1,4), and alkylation (1,4,7-9) reactions, always indicates a concurrence between electrophilic attack on the nitrogen atom and the -carbon atom in the enamine. Concerning the nucleophilic reactivity of the j3-carbon atom in enamines, Opitz and Griesinger (10) observed, in a study of salt formation, the following series of reactivities of the amine and carbonyl components pyrrolidine and hexamethylene imine s> piperidine > morpholine > cthyl-butylamine cyclopentanone s> cycloheptanone cyclooctanone > cyclohexanone monosubstituted acetaldehyde > disubstituted acetaldehyde. 

The trimer having been produced, protonation of the central pyrrolidine nitrogen occurs, and the formal positive charge then sufficiently retards further electrophilic attack on the two pyrrole nuclei to allow the isolation of tripyrrole. 

The nitrogen atoms in ADC compounds are highly electrophilic. Nucleophilic attack on nitrogen is easy, and as with electrophilic acetylenes, such as dimethyl acetylenedicarboxylate, it seems likely that some cycloaddition reactions of ADC compounds with unsymmetrical substrates proceed via a stepwise mechanism. PTAD is a powerful electrophile, although TCNE is more reactive, and chlorosulfonyl isocyanate is more reactive still.58... 

Diazines are generally resistant to electrophilic attack on carbon, and, as for pyridine, addition on nitrogen is observed. Alkyl halides give mono-quaternary salts di-quatemary salts are not formed under normal conditions. Of conrse, if the diazine ring carries a snbstitnent that makes the starting... 

Reactivity of Fuiiy Conjugated Rings 10.02.5.1 Electrophilic Attack on Carbon and Nitrogen... 

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