Pyrroles trisubstituted, formation

The addition of trithiazyl trichloride (NSC1)3 to 2,5-disubstituted furans and to N-2,5-trisubstituted pyrroles has led to the formation of isothiazole derivatives <96JHC1419>. 

It should be noted that the 1 1 adducts of benzyne with pyrrylmag-nesium iodide, and A -methyl- and iV-benzylpyrrole were isolated and characterized only as the hydrobromide (113), the methiodide (115), and the picrate of 102, respectively. The low yields of all these derivatives are due in part to further reactions of thenaphthalen-l,4-imines with benzyne (see Section III, F and G). Yields are better where the starting pjnrole has an electron-withdrawing N-substituent. Some analogous naphthalen-l,4-imines expected from 1,2,5-trisubstituted pyrroles apparently rearrange spontaneously to j3-naphthylamine derivatives under the conditions for their formation (see Section III, F). The related adducts 107 and 108 are formed from tetrahalobenzynes and N-methy Ipyrrole. 

Benzofuranyl)pyrroles, 2-(2-thienyl)pyrroles , 2,2 -dipyrroles, 3-(2-pyr-rolyl)indoles , 2-(2-benzimidazolyl)pyrroles and2-(2-, 3- and4-pyridyl)pyrroles were prepared using this method. Reaction of alkynes (for example, propyne) or allene with ketoximes in a superbase system (MOH/DMSO) leads to 2,5-di- or 2,3,5-trisubstituted pyrroles Pyrroles and dipyrroles were synthesized also from corresponding dioximes and acetylene in a KOH/DMSO system It has also been shown that 1,2-dichloroeth-ane can serve as a source of acetylene in pyrrole synthesis. Oxime 52 in the system acetylene/RbOH/DMSO at 70 °C afforded a mixture of three pyrroles 53-55 in low yields (equation 23). The formation of product 53 occurred through recyclization of pyrrolopy-ridine intermediate. ... 

Vinylpyrroles and 3-(3-pyrrolyl)propenoic acids (366 X = H or C02H) react under acid catalysis with trisubstituted pyrroles to yield the bispyrrolylethanes (367) and (368). The formation of (367) arises from the direct nucleophilic attack on the 3-vinyl group, whereas (368) results from the dissociation of the initial adduct to produce the 2-vinylpyrrole, which reacts further (58LA(611)205). The structures of the bispyrrolylethanes were established... 

The 3-vinylpyrroles (366 X = H or C02H) also react with electrophiles. No products were isolated, but it was suggested that the blue colouration produced upon the acid-catalyzed reaction with Ehrlich s reagent was due to the formation of (370) and that it was identical with that of the product obtained from the reaction of the trisubstituted pyrrole and the cinnamaldehyde. Similarly, the red colouration obtained from the reaction of (366 X = H or C02H) with diazotized sulfanilic acid was ascribed to the formation of (371) <58LA(611)205). 

Similar reaction conditions as those by Bose were used for a range of other applications, for example, the synthesis of heterocycles. A combination of a microwave-assisted Paal-Knorr reaction15 with a transfer hydrogenation takes place in the preparation of 2,5-di- and 1,2,5-trisubstituted pyrroles from -l,4-diaryl-2-butene-l,4-diones in a one-pot operation. Hydrogenation was achieved with ammonium formates and 10% Pd/C as catalyst in PEG-200. Yields of up to 92% were obtained within 0.5-2 min (Scheme 4.2)16. 

A titanium-catalyzed hydroamination of 1,4-diynes and 1,5-diynes produces 1,2,5-trisubstituted pyrrroles in one synthetic step <04OL2957>. Treatment of 1,4-diyne 33 with titanium complex 34 led to the formation of pyrrole 35 via a hydroamination to an imino alkyne followed by an intramolecular 5-endo dig cyclization. Another transition metal-mediated pyrrole... 

Cyclocondensation of nitroalkenes with CH-acidic isocyanides in the presence of bases leads to the formation of trisubstituted pyrroles 20 (Barton-Zard synthesis) [43] ... 

The enaminones 57a and b were found to react with fi-bromonitrostyrenes 124 in water, leading to the formation of a set of trisubstituted pyrroles 125 and 126, respectively, in 72-90% yield (Scheme 12.48) [72]. 

The cycloaddition of a-metalated methyl isocyanides onto the triple bond of electron-deficient acetylenes to 2,3,4-trisubstituted pyrroles in 17-97% yield was realized in de Meijere group (Scheme 8.6). Several copper could catalyze the polysubstituted pyrrole formation. Moreover, they also developed a new copper catalyst system for the synthesis of 2,3-disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides in 5-88% yield [16,17]. 

When formation of N-O-dvinyl hydroxylamine is favored, its [3,3]-rearrange-ment leads to 2,3,4-trisubstituted pyrroles while 1,3-prototropic shift to the O-l-propenyl oximes is hindered, [l,3]-sigmatropic rearrangement occurs to give 2,3,5-trisubstituted pyrrole (after cyclization of intermediate amino aldehyde) Scheme 1.143. 

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