Pyrrole isolation

Methylpyrrole is one of the four pyrroles isolated in the pyrolysis of trigonelline by Viani and Horman (1974). It was also formed by heating D-xylose with methylamine (Kato, 1966), from a cysteine/ cystine ribose browning system (Mulders, 1973c). Kato and Fujimaki (1968) observed the formation of A -substituted pyrrole-2-carbaldehydes when D-xylose reacted thermally with various amines or amino acids (glycine, alanine, 3-alanine, leucine). The intermediate 3,4-dideoxypentosulos-3-ene would either give 2-furaldehyde (mainly with a-amino acids) or substituted pyrrole-2-carbaldehydes and melanoidins (with 3-alanine or other amines). 

Pyrrole-2-carboxaldehyde (10 g, 0.1 mol) was dissolved in 300 mL of water in an Erlenmeyer flask. NaBH4 (11 g, 0.3 mol) was dissolved in 100 mL of water and added to the pyrrole-2-carboxaldehyde solution dropwise over a 10-min period. The mixture was allowed to stir at room temperature for 1 h. The reaction solution was then extracted with diethylether (3 x 100 mL), washed with satd NaaCOs (3 x 100 mL), and dried over MgS04 (anhydrous). The solvent was evaporated to yield 9 g of 2-(hydroxymethyl)pyrrole, isolated as a colorless oil (90% yield based on 10 g of the pyrrole-2-carboxaldehyde starting material). 

Although only ppm levels of nitrogen are found in the mid-distillates, both neutral and basic nitrogen compounds have been isolated and identified in fractions boiling below 345°C (12). Pyrroles and indoles account for about two-thirds of the nitrogen. The remaining nitrogen is found in the basic pyridine and quinoline compounds. Most of these compounds are alkylated. 

Table 1 Hsts the polyether antibiotics arranged by the number of carbons in the skeleton. Many of these compounds were isolated independendy in separate laboratories and thus have more than one designation. The groups are subdivided depending on the number of spiroketals. Two classes fall outside this scheme the pyrrole ether type containing a heterocycHc ring, and the acyltetronic acid type, that has an acyHdene tetronic acid instead of a carboxyHc acid. These compounds are ionophores and because of their common features are included as polyethers.

Pyrroles react with the conjugate acids of aldehydes and ketones to give carbinols (e.g. 67) which cannot normally be isolated but which undergo proton-catalyzed loss of water to give reactive electrophiles (e.g. 68). Subsequent reaction may lead to polymeric products, but in the case of reaction of pyrrole and acetone a cyclic tetramer (69) is formed in high yield. 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

Nicotelline, CjoHgNj. This base, isolated by Pictet and Rotschy, forms colourless needles, m.p. 147-8°, b.p. above 300° its aqueous solution is neutral to litmus. Unlike other tobacco bases it yields a sparingly soluble, crystalline dichromate. It does not decolorise acid permanganate, and appears not to be a pyrrole derivative. ... 

Several alkaloids have been recorded for plants of this sub-order. From Nymphoea alba Linn., Bures and Plzik isolated nymphoeine, C14H23O2N it is amorphous, has m.p. 76-7°, gives a hydrochloride, m.p. 230° (dec.), contains a hydroxyl group, appears to be a secondary base, and to contain a pyrrole ring. It is toxic to frogs and produces tetanus-like symptoms. 

From S. tuberosa, Loureiro, Lobstein and Grumbach obtained stemonine, C H3304N, m.p. 160 , [a]D 4- 76-5 , which gives pyrrole reactions and whose pharmacological action is described. (For another stemonine see p. 765.) Suzuki s investigation of the same plant led to a different result, the isolation of the alkaloid tuberostemonine. 

Dewar pyrrole [756] and Dewar thiophene stabilized by the presence of fluormated substituents have been successfully isolated, and their chemical pro perties have been studied [757, 1S8, 159, 160, 161] The olefinic bond m these... 

Despite its apparent simplicity, the PK pyrrole synthesis has retained its mystique since being discovered. Several investigations into the PK mechanism have been reported, including a gas phase study. Current evidence (intermediate isolation, kinetics, isotope effects) suggests the following (abbreviated) mechanism for the formation of pyrrole 13. However, the specific PK mechanism is often dependent on pH, solvent, and amine and dicarbonyl structure, especially with regard to the ringclosing step. 

Pyridine is a polar, stable, relatively unreactive liquid (bp 115°C) with a characteristic strong penetrating odor that is unpleasant to most people. It is miscible with both water and organic solvents. Pyridine was first isolated, like pyrrole, from bone pyrolysates. Its name is derived from the Greek for fire (pyr) and the suffix idine used to designate aromatic bases. Pyridine is used as a solvent, in addition to many other uses including products such as pharmaceuticals, vitamins, food flavorings, paints, dyes, rubber products, adhesives, insecticides, and herbicides. Pyridine can also be formed from the breakdown of many natural materials in the environment. 

Ciamician and Dennstedt reacted the potassium salt of pyrrole with chloroform in ether and isolated, after much purification, 3-chloropyridine, which was confirmed by crystallization with platinum. While the pyrrole salt can be used as the base, the chloroform carbene is typically formed with an alkali alcohol. Forty years later, Robinson and co-workers made 3-chloroquinolines from indoles using the Ciamician-Dennstedt reaction. ... 

Methylpyrrole and dimethyl acetylenedicarboxylate interact at 0°C to give a 1 2 adduct which is now known " to have structure (48). It is formed by addition of the ester across the 2,5-positions of the pyrrole yielding (47), which was not isolated but combined with a second molecule of the ester across the 2,7-positions accompanied by scission of the 4,7-bond as indicated. This adduct (48) was oxidized by bromine in methanol to trimethyl l-methylindole-2,3,4-tricarboxyl-ate and reacted further with hot dimethyl acetylenedicarboxylate. 

The classical age of preparative organic chemistry saw the exploration of the extensive field of five-membered heterocyclic aromatic systems. The stability of these systems, in contrast to saturated systems, is not necessarily affected by the accumulation of neighboring heteroatoms. In the series pyrrole, pyrazole, triazole, and tetrazole an increasing stability is observed in the presence of electrophiles and oxidants, and a natural next step was to attempt the synthesis of pentazole (1). However, pentazole has eluded the manifold and continual efforts to synthesize and isolate it. 

Pyrrole gives one 2-pyrrylidene isomer, but without activation a mixture of geometric isomers is isolated. 

One decade later, the parent compounds 21 were synthesized (78BCJ1427). For example, the reaction of 2-methylthio-l,3-dithiolium iodide with pyrrole gave 2-(2-pyrrolyl)-l,3-dithiolium iodide in a 92% yield, which on treatment with DBU gave 5-aza-l,4-dithiafulvalene 21 (R = H, Z = S, no Ph at dithiole-ring) as thermally stable orange crystals. Using the same type of reaction, the benzoderivatives of type 24 could be isolated (78BCJ1427). 

In 1970, Hiraoka reported that 2-cyanopyrrole, irradiated in methanol with a low-pressure mercury arc for 20 h, gave a mixture of 3-cyanopyrrole and pyrrole-2-carbaldehyde [70JCS(CC)1306]. l-Methyl-2-cyanopyrrole (38) also gave this reaction (Scheme 15) [71JCS(CC)1610]. In this case, the author isolated the product of the isomerization 39, the product of the shift in C-2 of the IV-methy 1 group 40, and a third product that was assumed to be derived from the addition of methanol to the Dewar pyrrole 41. The reaction depends on the temperature used in fact, no reaction occurred when the reaction was performed at -68°C. This result is in agreement with the presence of a thermal-activated step [78JCS(CC)131]. More... 

Azaferrocene reacts with aromatic hydrocarbons in the presence of aluminium chloride, giving rise to the cationic complexes of the type (Ti -arene)(Ti -cyclopenta-dienyl)iron(l+) isolated as BF4 salts [87JOM(333)71]. The complex 28 is obtained by reaction of the sulfane compound [Cp(SMc2)3Fe]BF4 with pentamethyl-pyrrole [88AG(E)579 88AG(E)1468 90ICA(170)155]. The metallic site in this center reveals expressed Lewis acidity (89CB1891). 

Pyrrole, then, polymerizes very readily in acid. By the controlled use of dry HCl in ether or of 6iY aqueous HCl for a few seconds, variable yields of a homogeneous trimer may be obtained. The isolation of pyrrole dimer has not yet been reported, although what may be a fairly homogeneous complex of dimer and SnCU has been described. Attempts to liberate the free base from this complex were unsuccessful. 

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 first question one asks is why does the reaction with 2-methyl-pyrrole stop at the dimer stage, whereas the pyrrole dimer itself cannot be isolated, but reacts further to form the trimer. The answer probably lies in the greater electrophilic reactivity of... 

A mechanism has been formulated, starting with a condensation to give the imine 4, that can tautomerize to the corresponding enamine 5. The latter can be isolated in some cases, thus supporting the formulated mechanism. A cyclization and subsequent dehydration leads to the imine 6, which tautomerizes to yield the aromatic pyrrole 3 ... 

Py rrolostatin is a novel lipid peroxidation inhibitor, which is isolated from Sirepinmyces diresinmyceiiois. Its stnicnire consists of a pyrrole-3-carboxyiic acid v/ith a geranyl group at the 4-posidon. It is readily prepared by applying the Barton-Zard pyrrole synthesis, as shown inEq. 10.33. ... 

Chlorophyll a, the green photosynthesis pigment, is the prototype of the chlorin (2,3-dihydro-porphyrin) class of products. It was first isolated by Willstatter1 at the turn of the century. The common structural unit in this class is the chlorin framework named after chlorophyll. The chromophore with a partially saturated pyrrole ring, which is formally derived from the completely unsaturated porphyrin, is less symmetric than the latter and systematically named according to IUPAC nomenclature as 2,3-dihydroporphyrin. 

Systematic investigations have deary demonstrated that in the presence of metal ions the conjugated hexahydroporphyrin forms are thermodynamically favored by complexation whereas in the absence of metal ions the porphyrinogen form with isolated aromatic pyrrole rings is the thermodynamically stable tautomer. 

As with the pyrroles, N-chloroamides have been widely employed in indole chlorination [66JOC2627 80H( 14)867 81JOC2054]. Chloroindolen-ines may be isolated under controlled conditions [80H( 14)867 81JOC2054], 2-Phenyl-, l-methyl-2-phenyl-and 3-methyl-2-phenyl-indoles were converted by 1-chloroisatin (NCI) into the 3-chloro derivatives... 

Kobayashi and Mutai75 have recently reported an interesting rearrangement of the 1,4-dithiin sulfone (53) to the thiophenes (54) and (55) (equation 12). While 54 presumably arises as a result of simple photoextrusion, the rearranged thiophene (55) is postulated to arise via the valence isomer (56), followed by cyclization to the thiophene, concomitant with, or preceded by, loss of S02. Some support for the intermediacy of the thioketone (56) was revealed by the isolation of the pyrrole (57), when the photolysis was conducted in n-butylamine. Compound 57 presumably arises by cyclization of the iV-butylimine analog of 56 initially formed. 

In 1968 DairOlio et al. published the first report of analogous electrosyntheses in other systems. They had observed the formation of brittle, filmlike pyrrole black on a Pt-electrode during the anodic oxidation of pyrrole in dilute sulphuric acid. Conductivity measurements carried out on the isolated solid state materials gave a value of 8 Scm . In addition, a strong ESR signal was evidence of a high number of unpaired spins. Earlier, in 1961, H. Lund had reported — in a virtually unobtainable publication — that PPy can be produced by electrochemical polymerization. 

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