Thienyl pyrrole derivatives

The reaction was performed in an autoclave under an initial acetylene pressure of 8-15 atm. The IR spectrum of 2-(2-thienyl)-pyrrole (23) and its N-vinyl derivative (24) displays characteristic bands of the thiophene... 

Crystallization of 2-(2-thienyl)pyrroles 125 produced gold-like and bronze-like metallic crystals <02BCJ2359, 02T10233>, while structurally related derivatives produced red-violet metallic crystals <02T10225>. A crystal structure analysis of 2,5-bis(4-biphenylyl)thiophene and the effect of structure on optical properties has been reported <02AM498>. 

Methyl-2-(2-thienyl)pyrrole 686 (X = S) reacted with tetracyanoethylene to yield the 3-tricyanovinyl isomer 687 along with 4-tricyanovinyl derivative 688 (Equation 165) <2001ARK37>. Under these conditions, 2-(2-furyl)-5-methylpyrrole 686 (X = O) behaved differently, namely, the major direction of the reaction with tetracyanoethylene involves the attack on the a-position of the furan ring giving rise to product 689 (Equation 165) <2001ARK37>. 

Aroyl- and thiophene-substituted pyrrole derivatives, for example, 45 (R = FI, Me, Et Ar = Ph, 2-thienyl, 4-CIC6H4, etc. Ar = Ph, 5-chloro-2-thienyl, 4-CIC6FI4, etc.) have been synthesized as a new class of COX-l/COX-2 inhibitors <2000EJM499>. iV-(Pyridin-3-ylmethyl)-3-[5-chloro-l-(4-chlorobenzyl)indol-3-yl]propanamide 46 represents one of the most potent compounds evaluated in the 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear swelling assay, with a level of activity higher than that of ibuprofen and comparable to that of dexametha-sone <2004BML5441>. 

The direct synthesis by anodic oxidation of a new series of electrically conducting poljnners is described.. Our polymers derive from sulfur and/or nitrogen containing hetero-cycles such as 2-(2-thienyl)pyrrole, thiazole, indole, and phthalazine. The anodic oxidation of these monomers is carried out in acetonitrile solutions containing tetrabu-tylammonium salts (TBA X ) ith X = BF, tetraethylammonium salt, TEA H C-C H -S0. Characterization of the materials by electrical conductivity, electron spin resonance, uv-visible spectroscopy, and cyclic voltammetry is discussed. 

Reaction of the derivative 149 (R1 = R2 = 2,5-dimethyl-3-thienyl) with DMF acetal gives the amidine 150 (85%) (Scheme 28) (01MI2424). Condensation of the derivatives 149 (R1, R2 = alkyl or aryl) with 2,5-dimethoxytetrahydrofuran, in the presence of 4-chloropyridinium chloride, gives the pyrrole derivatives 151 (25-86%) (Scheme 28) (96JHC2007, 98JHC1313). 

The reactivity of pyrrole and thiophene during copolymerization with their derivatives depends strongly on the oxidation potentials of the monomers. Accordingly, the use of a monomer feed of bithiophene and pyrrole is the optimum method for preparing thiophene/pyrrole copolymers. But the best route to thiophene/1-methylpyrrole copolymers is to homo-polymerize A/-methyl-2,5-di-(2-thienyl)-pyrrole. 

SCHEME 1.60 Synthesis of 3-alkyl-2-(2-thienyl)pyrroles and their N-vinyl derivatives from alkyl thienyl ketoximes and acetylene. 

It is pertinent to emphasize that the trifluoroacetylation of diverse pyrrole systems attracts the attention of researchers for a long time [1,2,623-625]. This reaction has frequently been used to compare the reactivity of pyrroles, furans, and thiophenes in electrophilic substitution processes [617,618,626]. The ratios of the trifluoroacetylation rates of these heterocycles with trifluoroacetylc anhydride are (5.3-10 ) (1.4-10 ) 1 [627]. Therefore, it is expected that 2-(2-furyl)- and 2-(2-thienyl)pyrroles and their N-vinyl derivatives will be acylated only at position 5 of the pyrrole ring (direction 1) (Scheme 2.168). 

Unlike 2-phenylpyrrole [615], 2-(2-furyl)- and 2-(2-thienyl)pyrroles are not tri-fluoroacetylated exhaustively under similar conditions the conversion is 50%-60% and the yields of the corresponding 5-trifluoroacetyl derivatives range from 40% to 50% (Table 2.16). The use of a twofold excess of the anhydride (relative to 2-(2-furyl)pyrrole) and increase of temperature (50°C) do not change by the reaction direction only 2-(2-furyl)-5-trifluoroacetylpyrrole is formed, although its yield raises to 75%. 

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. 

Formation of this ring system was also reported in the reaction of a,/3-unsaturated ketones with substituted pyrrol-5-ones, giving the tricyclic products in 41—46% yield <2004PS(179)61>. 4-Thienyl and 4-furyl derivatives of a dihydropyrano[2,3- 5,6-c]dipyrazole were also obtained via the heterocycle-substituted acrylonitrile in 77% and 74% yield, respectively <2005RJ0742>. 

Aromatic species include the neutral molecules pyrrole, furan and thiophene (1 Z = NH, O, S) and the pyrrole anion (2). The radicals derived from these rings are named pyrryl, furyl and thienyl. The 2-furylmethyl radical is called furfuryl. Compounds in which two pyrrole nuclei are joined by a CH2 group are called dipyrromethanes when the linkage is by a CH group, they are named dipyrromethenes . The 2- (3) and 3-pyrrolenines (4) are isomeric with the pyrroles, but are nonaromatic as the ring conjugation is broken by an. s/r -hybridized carbon atom. 

Fused pyrroles have been prepared by the condensation of an amino group with a suitably positioned carbonyl function. Thus, reduction of ethyl (3-nitro-2-thienyl)pyruvate (226) with tin(IV) chloride gave 5-ethoxycarbonyl thieno[3,2-6]pyrrole (47), by the spontaneous cyclization of the intermediate amino derivative (227 Scheme 76) (64JOC2160). The formation of indolo[3,2-6]indole (229), a dibenzannelated pyrrolopyrrole, by the cyclization of (228) with tin(IV) chloride (Scheme 77) is an example of a case where reduction of the imino function in the starting material is necessary before cyclization will occur (78AHC(22)183). 

The reaction of alkyl thienyl ketoximes with acetylene proceeds smoothly at 100-130°C and can be performed under both elevated and atmospheric pressure. Normally, yields of thienylpyrroles are 50-70% (Table XVII). The ratio of pyrroles and their N-vinyl derivatives formed in a synthesis can be controlled by the reaction conditions, i.e., time, temperature, and variation of alkali cation. 2-(2-Thienyl)-l-vinylpyrrole is more readily obtained in an autoclave under elevated acetylenic pressure and by heating the reagents (120°C) in the presence of KOH (17-30% of methyl... 

Synthesis of 2-[5-(l//-pyrrol-2-yl)-2-thienyl]-l//-pyrrole 1355, monomer for polyconjugated polymers, is based on the reaction of l,4-di(l//-pyrrol-2-yl)-l,4-butanedione 1354 with Lawesson s reagent (Equation 292) <1997CM2876>. Compound 1356 was prepared by Triton B-catalyzed condensation of 17/-pyrrole-2-carbaldehyde and the appropriate nitrile derivative (Equation 293). 

The groups of Hirao and Yokoyama have examined various new base pairs. Base-pairing partners for 6-thienylpurine nucleoside (114) have been examined. This does not form stable base pairs with thymidine as there is a steric clash between the thienyl group and the thymidine C4-oxo group, but specific base pairs are obtained with the pyridinone analogues (115). The 5 -triphosphates of the ribonucleoside derivatives (115) were incorporated specifically opposite (114) with T7 RNA polymerase. In addition, (115, R=phenylethynyl) was shown to stabilise an internal loop of a theophylline-binding RNA aptamer. " Pyrrole-2-carbaldehyde derivatives (116) also form specific base pairs with the... 

Pyridine, pyrrols and quinoline derivatives are found in Group 28. Thiazole, thiophenes, thiazolines and thienyl derivatives are summarised in Group 29. Among miscellaneous compounds Group 30 lists hydrogen sulphide and ammonia. In Group 31 we find aliphatic and aromatic hydrocarbons like limonene (Flavis 01.001, FEMA 2633). 

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