Methylpyrrole 2- formyl-5-

Modifications iaclude the use of P-ketoaldehydes as acetals, eg (9), which leads to loss of the formyl group (21) the product ia this example is 5-ethoxycarbonyl-2-methylpyrrole [3284-51 -3]. 

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... 

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]. 

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). 

As mentioned previously, the final cyclization step requires loss of one of the terminal methyl groups on the a,c-biladiene intermediate. Though no firm mechanistic details have been published on this procedure, which resembles the synthesis of symmetrically substituted dipyrrylmethanes from self-condensation of 2-bromo- or 2-acetoxy-methylpyrroles, it has been noted that cyclization of an a,c-biladiene (204) with vacant positions above the 1-and 19-methyl groups results in production of a formylporphyrin (205), the new formyl... 

Condensation of 5,5 -diunsubstituted dipyrrylmethanes (210) with one mole of a 2-formyl-5-methylpyrrole (211) affords high yields of tripyrroles (212), apparently uncontaminated with by-products due to reaction of the pyrrole at both ends of (210). The tripyrrole intermediates can then be reacted with a different formylpyrrole (213) to give the appropriate a,c-biladiene (214) cyclization then gives good yields of porphyrins (215) (Scheme 15) (73DOK(210)1090>. 

Examples of selective side-chain oxidation were reported for two reagents Ceric ammonium nitrate was found to convert 5-methylpyrrole-2-carboxylates to 5-formylpyrrole-2-carboxylates. <95TL4345> Several examples of oxidation of C2 and C3 methyl groups to formyl in 1-(phenylsulfonyl)indoles with Mn02 were reported. <95SC2407>... 

Other furans included methyl- 2-furfural [4], 2-acetylfuran [5], 2-propionylfuran [6], l-(2-furanyl)-2-propanone [7] and l-(-2-furanyl)-3-butanone [8]. Several alkylpyrazines were also found, with the 2,5-dimethyl [9] and 2-methy 1-5-ethyl [10] the most abundant derivatives, and some 2-acyl-l-methylpyrroles of which only the formyl [11] and acetyl [12] derivatives were conclusively identified. 

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-formyl-1-methylpyrrole and with 3-formylindole produces (443 Hetero = l-methyl-2-pyrrolyl, 3-indolyl), (444) and (445) under acidic conditions (76JHC83). 

Although an impressive number of alkaloids have been isolated from plant sources, only a few contain simple pyrrole rings. These include a series of tropane alkaloids from the bark of Erythroxylum vacciniifoUum, for example, 82, that share as common structural features a methylpyrrole moiety <2005JNP1153> methyl-(5-formyl-l//-pyrrole-2-yl) -hydroxybutyrate 83 from sweet chestnut seeds <2002MI22> and solsodomine A 84 and B 85 from the fresh berries of Solanum sodomaeum L. <1998JNP848>. The latter are the first pyrrole alkaloids from the genus Solanum. 

Huni and Frank66 found that, by oxidation of 2-formyl-3-ethyl-4-methylpyrrole a mixture of two pyrrolinones are obtained, although in small yields. By carrying out the oxidation of 2-formylpyrrole in water, succinimide was obtained.44... 

The time scale of the build-up and decay of the NOE is often such that it can be used to study processes that proceed appreciably more slowly than those aceessible to band-shape studies. This has been used in studies of restricted rotation in amides (205,214) the cis-trans equilibrium of 4-bromo-2-formyl-l-methylpyrrole (215) exchange in water solution of the system l-(T-pyrazolyl)ethanol-acetaldehyde (216) and the cis-trans equilibrium in 4-bromo-2-formylfuran. (217)... 

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