Bromopyrroles other

Although pyrrolyl halides are well-known compounds, their instability to acid, alkali, and heat precludes their commercial availability. Since pyrrole is a very reactive, Jt-excessive heterocycle, it undergoes halogenation extremely readily [6, 7], For example, the labile 2-bromopyrrole, which decomposes above room temperature, is a well-known compound, as are A-aIkyl-2-halopyrroles, readily prepared by direct halogenation, usually with NBS for the synthesis of bromopyrroles [8, 9], The 2-halopyrrole is usually the kinetic product but the 3-halopyrrole is often the thermodynamic product, and this property of halopyrroles can be exploited in synthesis. For example, A-benzylpyrrole (1) can be dibrominated to give 2 as the kinetic product, which rearranges to 3 upon treatment with acid [10, 11]. Other A-alkyl-2,5-dibromopyrroles are available in this fashion. 

Other examples of N-substituted 3-bromopyrroles that have been successfully derivatized at the 3-position include either 4- or 5-substituted-3-bromo-l-tosylpyrroles 5 (90TL6785 91T7615) 3-bromo-l-tritylpyrrole 6 (91UP1) and the bromo-azafulvene dimer , which leads to 4-substituted pyrrole-2-carboxaldehydes 8 after reaction with electrophiles and hydrolysis (88TL3215). 

Bromopyrrole-2-carbamide (116) was isolated from the Papua New Guinean sponge Agelas nakamurai. It exhibits antimicrobial activity against Staphylococcus aureus (IC50 0.78 pg/ml) and other bacteria and fungi [92]. 

A novel Pd-catalyzed asymmetric annulation was reported between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines <07OL2357>. The resulting pyrrolopiperazinones such as 58 served as key intermediates in the enantioselective synthesis of longamide B and a number of other pyrrole alkaloids. 

Bromination of Aromatic Compounds. Phenols, anilines, and other electron-rich aromatic corrqiounds can be monobromi-nated using NBS in DMF with higher yields and higher levels of para selectivity than with Br2 iV-TrimethyIsilylanilines and aromatic ethers are also selectively brominated by NBS in CHCI3 or ecu. A-Substituted pyrroles are brominated with NBS in THF to afford 2-bromopyrroles (1 equiv) or 2,5-dibromopyrroles (2 equiv) with high selectivity, whereas bromination with Br2 affords the thermodynamically more stable 3-bromopyrroles. The use of NBS in DMF also achieves the controlled bromination of imidazole and nitroimidazole. Thiophenes are also selectively brominated in the 2-position using NBS in acetic acid-chloroform. ... 

Acid-mediated hydrolysis of 5-halopyrrole-2-carboxylates provides access to 5-carboxy-3-pyrrolin-2-ones, but this transformation often lacks the regioselectivity of other methods. This reaction was first reported by Siedel (1943LAC144). In a more recent example, Battersby and coworkers have treated 5-bromopyrrole-2-carboxylate 548 with sulfuric add in methanol, and a mixture of 3-pyrrolin-2-ones 549 and 550 was obtained in low yield (Scheme 156 1988PT(1)1557). These reaction conditions led to both hydrolysis of the bromine and deprotection of the <-butyl ester followed by decarboxylation. In a related reaction involving a symmetrical substrate, Lugtenberg and de Groot converted 5-bromo-2-trichloroacetyl-3,4-dime-thylpyrrole into 3,4-dimethyl-3-pyrrolin-2-one via treatment with NaOH (1982MI2). 

Benzosceptrins A-C are other dimeric bromopyrrole alkaloids with a unique benzo-cyclobutane moiety. Benzo-sceptrin A was isolated from a Halichondrid sponge of the genus Phakellia collected around Solomon Islands, and benzosceptrins B and C were isolated from a New Caledonian and a Japanese (Okinawa) Agelas sp. (Appenzeller et al, 2009 Kubota et al, 2009). 

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