Nucleophiles pyrrole

Thus, pyrrole and acetone react as shown above. This involves pyrrole acting as the nucleophile to attack the protonated ketone in an aldol-like reaction. This is followed by elimination of water, facilitated by the acidic conditions. This gives an intermediate alkylidene pyrrolium cation, a highly reactive electrophile that reacts with another molecule of nucleophilic pyrrole. We then have a repeat sequence of reactions, in which further acetone and pyrrole molecules are incorporated. The presence of the two methyl substituents from acetone forces the growing polymer to adopt a planar array, and this eventually leads to a cyclic tetramer, the terminal pyrrole attacking the alkylidene pyrrolium cation at the other end of the chain. 

When the p-ketoamide 133, containing an acidic methine group and pendant nucleophilic pyrrole substituent, was dissolved with methyl vinyl ketone (53) in dichloromethane and treated at room temperature with PS-BEMP (10%), the Michael adduct 134 was formed as the sole reaction product in 100% yield. 

Table 21.1 clearly shows that complex [a Ti Ti -(OCH2)(Me2NCH2)C2B9H9]Ti(NMe2) (7.1-3a) is a very robust, effective, and elegant catalyst for the addition of primary and secondary aliphatic and aromatic amines to carbodiimides with good functional group tolerance. It also works very well for less nucleophilic pyrrole, indole, and benzotriazole. ... 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

Pyrrole, furan or thiophene do not react with nucleophilic reagents by substitution or addition but only by proton transfer. However, it should be noted that protonated pyrroles are susceptible to nucleophilic attack (see Section 3.02.2.4.5). 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

The rearrangement of thiophenes to the isomeric pyrroles has proven synthetically useful (Schemes 98a and 98b). In the absence of a suitable internal nucleophilic nitrogen, so-called degenerate ring transformations may occur (Schemes 98c and 98d). 

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. 

Azirines react with enolate anions. Initial nucleophilic attack on phenyl 1-azirine by the enolate anion derived from acetophenone gives intermediate (223) which undergoes 1,2-bond cleavage, cyclization and hydroxyl group elimination to give pyrrole (226). 

Imidazolium halides pyrolysis, 5, 449 Imidazolium ions acylation, 5, 402 H NMR, 5, 352 hydrogen exchange, 5, 417 nucleophilic attack, 5, 375 reactivity, 5, 375 ring opening, S, 375 Imidazolium oxides in pyrrole synthesis, 4, 344 Imidazolium perchlorate, 1,3-diphenyl-acylation, 5, 402 Imidazolium salts 1-acetyl-... 

N-alkylation, 4, 236 Pyrrole, 2-formyl-3,4-diiodo-synthesis, 4, 216 Pyrrole, 2-formyl-1-methyl-conformation, 4, 193 Pyrrole, 2-formyl-5-nitro-conformation, 4, 193 Pyrrole, furyl-rotamers, 4, 546 Pyrrole, 2-(2-furyl)-conformation, 4, 32 Pyrrole, 2-halo-reactions, 4, 78 Pyrrole, 3-halo-reactions, 4, 78 Pyrrole, 2-halomethyl-nucleophilic substitution, 4, 274 reactions, 4, 275 Pyrrole, hydroxy-synthesis, 4, 97 Pyrrole, 1-hydroxy-cycloaddition reactions, 4, 303 deoxygenation, 4, 304 synthesis, 4, 126, 363 tautomerism, 4, 35, 197 Pyrrole, 2-hydroxy-reactions, 4, 76 tautomerism, 4, 36, 198... 

Benzyl carbamates of pyrrole-type nitrogens can be cleaVfed with nucleophilic reagents such as hydrazine hydrogenation and HF treatment are also effective. ... 

Weak nucleophiles attack the 2-position with ring opening to form pyrrole derivatives after cyclization. The bromopseudooxazalone 62a yields the pyrroline 65 in methanolic potassium carbonate. 

Organometallic chemistry of pyrrole is characterized by a delicate balance of the ti N)- and -coordination modes. Azacymantrene is an illustration of the considerable nucleophilicity of the heteroatom. However, azaferrocene can be alkylated at C2 and C3 sites. Ruthenium and osmium, rhodium, and iridium chemistry revealed the bridging function of pyrroles, including zwitterionic and pyrrolyne complex formation. The ti (CC) coordination of osmium(2- -) allows versatile derivatizations of the heteroring. 

The foregoing examples show that the nucleophilic attack to nitroarenes at theorr/io-posidcn followed by cyclizadon is a generid method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion dedved from ethyl isocyanoacetate as the reacdve anion for the preparadon of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyriirddines depending on the stnicture of nitroarenes fEqs. 9.56 and9.57. The synthesis of pyrroles is discussed in detail in Chapter 10. 

Heterocyclic aromatic nitro compounds are more reactive toward nucleophiles than carbo-cyclic aromatic nitro compounds Various heterocyclic aromatic nitro compounds are thus converted into the corresponding pyrroles by the Barton-Zard reaction fEq 10 37 ... 

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