Substituted pyrroles ethyl

Pyrrolealdehyde has been prepared from pyrrole, chloroform, and potassium hydroxide from pyrrolemagnesium iodide and ethyl, propyl, or isoamyl formate and, by the method here described, from pyrrole, phosphorus oxychloride, and dimethylformamide. Smith has suggested a possible intermediate in this process. The method has also been applied to substituted pyrroles and is similar to that described in this series for the preparation of -dimethylaminobenzaldehyde from di-methylaniline. ... 

Cold, aqueous sodium hydroxide brings about the collapse of diethyl 2,7-dimelhyl-4//-azepine-3,6-dicarboxylate (3) to the 1-substituted pyrrole 4,29 whereas with aqueous ethanolic ammonia solution ring contraction is accompanied by loss of the butenoic acid side chain and formation of ethyl 2-methylpyrrole-3-carboxylate (94% mp 77-78cC). 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

Recently, the synthesis of 5-aryl-2-oxopyrrole derivative 210 as synthon for the highly substituted pyrrole 211 as starting compound for fused heterocycle 212 was published [56], Diethyl 6-bcnzyl-5-phenyl-6//-thieno[2,3-/ ]pyrrolc-2,4-dicarboxylatc 212 was prepared from ethyl l-benzyl-5-chloro-4-formyl-2-phcnyl-l //-pyrrolc-3-carboxylate 211 and ethyl 2-sulfanylacetate in refluxing ethanol (Scheme 41). 

Several new routes involve formation of one carbon-carbon bond in pre-formed substrates. Palladium-catalyzed cyclization of /3-hydroxyenamine derivatives has been employed in a route to substituted pyrroles and 4,5,6,7-tetrahy-droindoles with multiple substituents by formation of the C-3-C-4 bond as the key feature, as illustrated by construction of the molecule 534 (Equation 146) <2006T8533>. Zinc perchlorate-catalyzed addition of alcohols to the nitrile functionality of a-cyanomethyl-/3-ketoesters, followed by annulation gave access to a series of substituted ethyl 5-alkoxypyrrole-3-carboxylates <2007T461>. Similar chemistry has also been used for synthesis of a related set of pyrrole-3-phosphonates <2007T4156>. A study on preparation of 3,5,7-functionalized indoles by Heck cyclization of suitable A-allyl substituted 2-haloanilines has also appeared <2006S3467>. In addition, indole-3-acetic acid derivatives have been prepared by base induced annulation of 2-aminocinnamic acid esters (available for instance from 2-iodoani-lines) <2006OL4473>. 

Synthesis of bis(pyrrole) monomers. The condensation of ethyl diacetyl succinate with amines to give dialkyl esters of N substituted pyrroles proceeds in near quantitative yields to the bis(dicarboethoxy dimethyl pyrrole). 

Pyrrole reacts with aqueous formaldehyde and secondary amines in the presence of acetic acid to afford, in some cases, mixtures of products derived from attack at the 2- and 2,5-positions. The disubstitution products can be obtained in very high yields at about room temperature for example, a 92% yield of 2,5-bis(piperidylmethyl)pyrrole is obtained using this method. The same procedure apparently does not yield a Mannich base with l-methylpyrrole, but the use of aqueous formaldehyde and dimethylamine hydrochloride at 60 °C results in the formation of the 2-substitution product in 73% yield. Even highly substituted pyrroles react. Thus, ethyl 4,5-dimethylpyrrole-2-carboxylate and ethyl 2,5-dimethylpyrrole-3-carboxylate both undergo C-aminoalkylation at the unsubstituted position in 45 and 68% yields, respectively, with dimethylamine and formaldehyde in ethanolic solution. A number of tri- and tetra-substituted 2-methylpyrroles have been investigated with the exception of Knorr s pyrrole all gave side-chain substituted products with formaldehyde and a secondary amine in acetic acid. ... 

A similar synthesis to give octaacetic acid porphyrin is much less productive (Chiusoli et al., 1989). Highly substituted porphyrins with eight P-pyrrolic ethyl groups and four phenyl groups in the meso positions have been obtained similarly. The latter, highly overcrowded porphyrins (see chlorophyll synthesis) are totally stable (Evans et al., 1977). 

The Paal-Knorr cyclization was employed to produce highly aryl-substituted pyrrole carboxylates as useful medicinal chemistry leads. Therefore, l,4-diketone-2,3-diester was assembled from an Sn2 displacement of ethyl 2-bromoacetoacetate with the anion of the ketoester. Condensation with an aniline then provided a library of fully substituted pyrroles. 

While a 2-(D-arabino-tetritol-l-yl)-l-methylpyrazole derivative was obtained from the condensation of 2-deoxy-2-methylamino-D-glucose with ethyl acetoacetate (c.f. Vol.l4, p.89), the 3-substituted pyrrole analogues (72) were obtained from 1-deoxy-l-raethylamino-... 

Many compounds have been reported in the literature to be chemical antiozonants, and nearly all contain nitrogen. Compound classes include derivatives of 2,2,4-trimethyl-l, 2-dihydroquinoline, N-substituted ureas or thioureas, substituted pyrroles, and nickel or zinc dithiocarbamate salts. The most effective antiozonants, however, are derivatives of p-phenylenediamine (p-PDA). The commercial materials are grouped into three classes N,N -dialkyl-p-PDAs, Nalkyl-N -ary 1-p-PDAs, and NX-diary 1-p-PI) As. The NX-dialkyl-p-PDAs (where the alkyl group may be 1-methylheptyl, l-ethyl-3-methylpentyl, 1,4-dimethylpentyl, or cyclohexyl) are the most effective in terms of their reactivity to ozone. These derivatives increase the critical stress required for the initiation of crack growth, and they also reduce the rate of crack growth significantly. The sec-alkyl group is most active, for reasons that are not yet completely clear. The drawbacks of these derivatives are ... 

C-2 substituted pyrroles 93 and 94 were obtained in fair yields when a tandem palladium-catalyzed C—H functionalization of ethyl diazoacetate... 

Polypyrrole can also be synthesized with substituents on the nitrogen. However, these substitutions can dramatically alter the properties of the films and have deleterious effects on their conductivities. For example, although poly- V-methylpyrrole has an appearance and level of doping similar to those of polypyrrole, the conductivity is diminished to 10 S cm" [4]. PoIy-A -methylpyrrole has an oxidation potential of 0.45 V (versus SCE), a positive shift of 0.65 V compared with polypyrrole. In general, N-substituted polypyrroles are more difficult to oxidize and correspondingly less air sensitive than the parent polymer [119]. Substituted pyrroles with ethyl, propyl, or butyl groups attached to the nitrogen can also... 

A mixture of amine (1 5 mmol), 1,4-dicarbonyl compound (2 6 mmol), and sulfamic acid (25 mg, 5 mol%) was stirred at room temperature under solvent-free conditions for specified period (30-90 min for varying entries). After completion of the reaction, as indicated by thin-layer chromatography (TLC), the reaction mixture was diluted with diethyl ether and filtered to recover the catalyst. The ether layer was washed with brine, dried (MgS04), and coti-centrated in vacuo. The residue was purified by silica-gel column chromatography (20% ethyl acetate in hexane) to afford the desired substituted pyrrole (3) in excellent yield (81-93%). The recovered catalyst was washed with diethyl ether and activated at 70 "C prior to reuse it could be reused for the next reaction without losing any significant activity as tested for at least three times. All the products were characterized by H NMR, HRMS and analytical data. 

Rhodium catalyzed reactions of ethyl isocyanoacetate 353 with 3-fluoroacetylacetone 352 provides a new facile method for the catalytic synthesis of substituted pyrroles. The key step of the reaction is the activation of the C-H bond of isonitrile 353 induced by the a-heteroatom effect. 3-Fluoropyrrole 44 was obtained in 40 % by this method [115]. The mechanism of the transformation includes rhodium promoted decarbonylation of formamide 354 followed by cyclocondensation of intermediate 355 to form the corresponding pyrrole 44. 

Hoffmann MG, Wenkert E (1993) Natural product synthesis in agricultural chemistry. 2. A new and efficient synthesis of 2-trifluoromethyl substituted pyrroles and ethyl-2,3-bis(ethoxycarbonyl)-lH-pyrrole-1-propionate. Tetrahedron 49 1057-1062... 

Fischer and Treibs used the differing basicities of substituted pyrroles to effect separations by means of hydriodic acid. 2,3,4-Trimethylpyrrole gave a crystalline hydrochloride, and with hydrobromic in acetic acid, crypto-pyrrolecarboxylic (2,4-dimethylpyrrole-3-j3-propionic) and related acids gave hydrobromides which could be recrystallized from acetic acid. Cookson showed that addition of hydrochloric acid to an alcoholic solution of cryptopyrrole (3-ethyl-2,4-dimethylpyrrole) removed the ultra-violet absorption band at 200 m[i, and produced a new maximum at 261 m(x (e, 4,000). The acid solution was stable for at least 10 min and the spectrum reverted to its original form upon addition of alkali. Other pyrroles with electron-attracting substituents did not show these changes which are clearly due to salt formation. 

For preparative purposes the Gattermann reaction is much more useful. It was first usedS5 to prepare ethyl 2-formyl-3,5-dimethyl- and ethyl 3-formyl-2,5-dimethyl-pyrrole-4-carboxylate, by means of hydrogen cyanide and hydrogen chloride in ether. Later applications sometimes involved minor changes such as the use of chloroform as solvent, or of Adams modification of the reaction . Formylation generally occurs at an a-position, but if none is open there is usually no difficulty in jS-substitution. Pyrrole-2-aldehyde cannot be made this way, for it reacts further to form dyestuffs, but several 1-alkylpyrroles have been satisfactorily formylated . The initial... 

C-Acylation and -carboxylation also occur with pyrrole Grignard reagents (p. 106). Whilst lithium pyrrole and lithium 2,4-dimethylpyrrole react with ethoxycarbonyl chloride to give ethyl pyrrole-2- and 2,4-dimethylpyrrole-5-carboxylate, respectively the corresponding potassium salts give the N-substituted pyrroles (p. 81). 

Substituted pyrroles such as ethyl 2,4-dimethyl-3- or 2,5-dimethyl-3-carboxylate are hydroxymethylated at the empty nuclear position by formalin and sodium hydroxide or potassium cyanide . Similarly, the initial carbinols from pyrroles and aldehydes can he isolated if they are stabilized in any other way an example is the carbinol (17) which, like others of its class, can be obtained from the appropriate pyrrole and chloral hydrate in the presence of hydrochloric acid . 

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