Aroyl pyrroles

Condensation of an MSMA isonitrile with an aroylfluoride gives a salt which undergoes loss of trimethylsilyl fluoride to form a nitrile ylid. This transient species reacts with DMAD to form 2-aroyl pyrrole in high yield.162 Substitution of acyl chloride for acyl fluoride in the reaction affords only poor yields of adducts.465... 

The large class of antiinflammatory phenylacetic acids are treated at some length in Chapter 4. A number of these agents consist of acetic or propionic acids substituted "by an aroyl group. It is of interest that the central benzene ring of these molecules can be replaced by pyrrole with retention of activity. 

Furo[3,4-c]pyrrolediones are important intermediates in the synthesis of diketo-pyrrolopyrrole (DPP) pigments. Smith and coworkers have described the preparation of several different 3,6-diaryl-substituted furo[3,4-c]pyrrole-l,4-diones by microwave-assisted cyclization of readily available 4-aroyl-4,5-dihydro-5-oxo-2-arylpyrrole-3-carboxylates (Scheme 6.192) [353]. While conventional heating in Dowtherm A at 230-240 °C for 64 h provided only moderate product yields, microwave irradiation of the neat starting material at 250 °C for 10 min provided significantly increased yields. 

Itahara has also found that the phenylation of A-aroylpyrroles can be achieved using Pd(OAc>2 [30, 31]. Although A-benzoylpyrrole (22) yields a mixture of diphenylpyrrole 23, cyclized pyrrole 24, and bipyrrolyl 25 as shown, l-(2,6-dichlorobenzoyl)pyrrole 26 gives the diphenylated pyrrole 27 in excellent yield. The IV-aroyl groups are readily cleaved with aqueous alkali and the arylation reaction also proceeds with p-xylene and p-dichlorobenzene. Unfortunately, N-methyl-, iV-acetyl-, and A-(phenoxycarbonyl)pyrroles give complex mixtures of products. 

Massa, S., Mai, A., Sbardella, G Esposito, M., Ragno, R., Loidl, P. et al. (2001) G. 3-(4-Aroyl-lH-pyrrol-2-yl)-N-hydroxy-2-propenamides, a new class of synthetic histone deacetylase inhibitors. Journal of Medicinal Chemistry, 44, 2069—2072. 

Franco, F. F., Greenhouse, R., Muchowski, J. M., Novel syntheses of 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids, J. Org. Chem. 1982, 47, 1682-1688. 

The presence of an aroyl fragment in azomethine ylides obtained from opening of three-membered rings in the case of dipolarophiles with high LUMO (lowest unoccupied molecular orbital) energy or in the absence of an external dipolarophile can lead to the possibility of such unusual reactions as intramolecular 1,3-dipolar cycloaddition [80]. Examples of such reactions are the thermal isomerization of aroyl aziridines 63 into a pyrrole derivative 64 [81, 82] or into 2,5-diphenyloxazole 65 (in the presence of diphenyliodonium iodide) [83] (Scheme 1.16). 

Reaction of pyrroles 205 with 3-phenylprop-2-ynenitrile and l-aroyl-2-phenylethynes proceeds smoothly and... 

In recent years, the addition of pyrroles as C-nucleophiles to the electron-deficient triple bond has been extensively studied because this reaction provides the most direct approach to functionally substituted C-vinylpyrroles. Thus, the noncatalytic reactions of pyrroles 632 with terminal aroyl ethynes 633 proceeded under mild conditions either without a... 

The reactions of the pyrroles 632 with l-aroyl-2-phenyl ethynes 635 (R = Ph, 2-furyl) in the superbase KOH/DMSO system afforded a mixture of N- 637 ((E)- and (Z)-isomers) and C- 638 ((Z)-isomers) adducts, in a total yield of60-80%, the ratio of the products being dependent on the structure of the starting pyrrole (Equation 151) <2003RJ01195,2003S1272>. 

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>. 

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