2- -l-methylpyrrol

In contrast, 2-(l-methylpyrrol-2-yl)propene 42e afforded an ene adduct 241 [85JCR(S)12]. 

Methylpyrazine (300) gave 2-[2-(l-methylpyrrol-2-yl)vinyl]pyrazine (299) [NaH, Me2NCHO, 60°C, N2, 1 h then l-methyl-2-pyrrolecarbaldehyde J, 50°C, 5 h 40% compare conditions with those required for alkylidenation of the more activated methyl group in substrate (297)].1485... 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

The products were trimethyl hemimellitate (49) and trimethyl l-methylpyrrole-2,3,4-tricarboxylate (50), which were presumably... 

Tricarbonyl(l-methylpyrrole)chromium(0) (Tricarbonyl[(l,2,3,4,5- /)-l-mcthyl-l//-pyrrolc]chromium)... 

The principal products of irradiation of 2-cyano-l-methylpyrrole (166) in methanol, however, are the corresponding 3-cyanopyrrole 167 and the methanol adduct 168.129 These products appear to arise by a 2,5-bonding process followed by a thermal walk rearrangement as shown in Scheme 5. 

Similarly, 4-acetyl-2-(l,4-anhydro-D-ara fno-tetrahydroxybutyl)-5-methyl-pyrrole has been oxidized to 2-(4-acetyl-5-methylpyrrole-2)diglyoolaldehyde.S0... 

Reaction of l-Methylpyrrole-2-acetonitrile 43 with 6 New Efficient Synthesis of Highly Substituted Indoles (Type-IV, 4a Model)... 

Various iodinated pyiToles have been prepared by direct iodination [19,24] or via thallation [25]. For example, 3-iodo-V-TIPS-pyrrole is prepared in 61% yield from 6 [19], and 3,4-diiodo-2-formyl-l-methylpyrrole is available in 54% yield via a bis-thallation reaction [25]. 

A Heck coupling of 2-lithio-l-methylpyrrole and bromohydrin 153 affords 154 [112]. 

Reaction of 2-aminopyrroles with equimolar amounts of dimethyl sulphate under phase-transfer catalysed basic conditions produces the 2-amino-1-methylpyrrole in good yield [17]. When two equivalents of the alkylating agent are used, a mixture of the mono- and dimethylamino-l-methylpyrroles and 2-amino-1-methylpyrroles is obtained. 

Tolmetin Tohnetin, l-methyl-5-n-tolylpyrrol-2-acetic acid (3.2.61) is synthesized from 1-methylindole, which is aminomethylated using formaldehyde and dimethylamine, forming 2-dimethylaminomethyl-l-methylindol (3.2.57). The product is methylated by methyl iodide, giving the corresponding quaternary salt (3.2.58). Reaction of the product with sodium cyanide gives l-methylpyrrole-2-acetonitrile (3.2.59), which is acylated at the free... 

In addition to the parent heterocycle, both AT,N-diethyl-l-methylpyr-role-3-carboxamide and l-methylpyrrole-3-carboxaldehyde have been selectively a-lithiated in the 2-position (85TL6213 87JOC104), the latter compound via the intermediacy of an a-(Af-methylpiperazino) alkoxide (Scheme 6). The a-amino alkoxide is formed in situ, via the addition of... 

Tetrachloro-l-methylpyrrole is fluorinated92 with potassium tetrafluorocobalt-ate(III) at 180°C to give a mixture (ca. 60% yield) of 3,4-dichloro-2,2,5,5-tetrafluoro-l-methyl-2,5-dihydropyrrole (1) and 3,4-dichloro-2,2,5,5-tetrafluoro-l-(fluoromethyl)-2,5-dihydropyr-role (2). 

Formylation of 2-methoxycarbonyl-l-methylpyrrole with dichloromethyl methyl ether and aluminum chloride occurs in the 4-position, while under Vilsmeier conditions the main product is the 5-formyl derivative (78JOC4849). 

The products of the base-catalyzed Stobbe condensation of 3-formylindole and of 2-formylpyrroles undergo acid-catalyzed cyclization to yield l-hydroxycarbazole-3-carboxylic esters and 4-hydroxyindole-6-carboxylic esters, respectively (73JPR295, 74JPR386, 76JPR816). The analogous condensation of dimethyl homophthalate with 2-formyi-l-methylpyrrole and with 3-formylindole produces (443 Hetero= l-methyl-2-pyrrolyl, 3-indolyl), (444) and (445) under acidic conditions (76JHC83). 

Scheme 2 Synthesis of 4-(fert-Butoxycarbonylamino)-l-methylpyrrole-2-carboxylic Acid A Heterocyclic Subunit for Several Naturally Occurring Oligopeptidesl101...

Methyl 4-Amino-l-methylpyrrole-2-carboxylate Hydrochloride Salt (5) 1 01... 

Methyl 4-amino-l-methylpyrrole-2-carboxylate hydrochloride (5 340 g, 1.78 mol) was dissolved in 10% aq Na2C03 (1L) in a 3-L flask equipped with a mechanical stirrer Boc20 (400 g, 1.83 mol) slurried in dioxane (500 mL) was added over a period of 30 min while a temperature of 20 °C was maintained. The reaction was allowed to proceed for 3 h and was determined complete by TLC the mixture was cooled to 5 °C for 2 h and the resulting white precipitate collected by filtration. The product, which was contaminated with Boc20, was used without further purification for the next step. 

Crude methyl 4-(ferf-butoxycarbonylamino)-l-methylpyrrole-2-carboxylate (6) from the previous step was dissolved in MeOH (700 mL) 2M NaOH (700 mL) was added and the soln was heated at 60 °C for 6h. The mixture was cooled to rt and washed with Et20 (4x1 L), the pH of the aqueous layer lowered to ca. 3 with 10% H2S04, and the mixture was extracted with EtOAc (4 x 2000 mL). The combined EtOAc extracts were dried (Na2S04) and concentrated under reduced pressure to provide a tan foam. The foam was dissolved in CH2C12 (500 mL) and petroleum ether (2 L) added, and the resulting slurry was concentrated. The residue was redissolved and concentrated three additional times to provide 7 as a fine white powder yield 320 g (75% from 5). 

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