Dioximes of 1,3-Diketones in the Trofimov Reaction: New 3-Substituted Pyrroles

Abstract

Dioximes of 1,3-diketones enter into the Trofimov reaction forming pyrroles containing an acyl or an O-vinyloxime substituent in position 3 of the pyrrole. In the case of sterically hindered dioximes the main reaction products are isoxazoles.Heterocyclic compounds containing a 3-acylpyrrole fragment are of interest for making new pharmacological preparations. For example, the cannabinoid activity of 1-alkyl-3-(naphthoyl)pyrroles [1] and 1-alkyl-3-(naphthoyl)indoles [2] is known, as is the antibiotic activity of verrucarin E, 3-acetyl-4-hydroxymethylpyrrole, isolated from Myrothecium verrucaria [3]. 3-Acylpyrroles and other 3-substituted pyrroles obtained from them are precursors of liquid crystal materials [4] and polypyrroles [5], possessing high electrical conductivity in comparison with their 1-substituted analogs [6]. Such conjugated polymers may be used for example to construct gas sensors [7], and also sensors capable of distinguishing DNA molecules [8].The acylation reaction used in the majority of cases for the synthesis of 3-acylpyrroles has low efficiency since electrophilic attack occurs predominantly at position 2 of the pyrrole ring. To direct substitution to position 3 it is necessary to introduce readily removable blocking groups into position 2 (a thiocarboxylate group [9]) or position 1 (triisopropylsilyl [10, 11], 1-phenylsulfonyl or 1-tosylsulfonyl [7,12, 13]).In the present work we have studied the possibility of synthesizing new 3-functionalized pyrroles with the aid of the Trofimov reaction [14-19] by the interaction of dioximes of acetylacetone (1a), benzoylacetone (1b), 5-ethylnonane-4,6-dione (1c), and 5,5-dimethylcyclohexane-1,3-dione (dimedone) (1d) with acetylene in the presence of KOH in DMSO.The selectivity of the interaction of dioxime 1a with acetylene depends strongly on the reaction temperature. At 100°C (1 h) the O-vinyloxime pyrrole derivative 2a is formed exclusively (11% yield), and at 120°C (1 h) the main product is the 2,3'-bipyrrole 3 (7% yield).Attention is attracted by the unusually high stability of the O-vinyloxime group of compound 2a under the reaction conditions. The formation of a second pyrrole ring with its participation occurs only on increasing the temperature to 120°C. It is known that for O-vinyloximes of 3-acylindoles pyrrolization in the system KOH-DMSO is also hindered and at 100-105°C occurs completely only after 8-10 h [20]. The reduced reactivity of the O-vinyloxime function at position 3 of the pyrrole ring in O-vinyloximes of 3-acylindoles __________________________________________________________________________________________ A. E.

Chiral molecules containing the pyrrole framework

“…52) in low yields. 171 The two pyrrole rings are non-planar and it was argued that the formation of the second pyrrolic ring from O-vinyloxime 227 was hindered due to the increased electron density at the 3-position of the existing pyrrolic ring compared with that at the 2-position. It was suggested that the bipyrrole formation occurs following a [3,3] sigmatropic rearrangement of an enehydroxylamine and that the electron-donating effect of the heterocycle on the O-vinyloxime 227 leads to a reduction of the C-H acidity of the neighbouring methyl group, which is unfavourable for tautomeric conversion of the vinyloxime into an enehydroxylamine.…”

Lewis Acid-Catalyzed One-Pot, Three-Component Route to Chiral 3,3‘-Bipyrroles

“…Hinz et al have synthesized 2,2‘-bipyrrole using pyrolysis of 2-azido-5-(2-pyrrolyl)penta-2,4-dienoic esters. Apart from 2,2‘-bipyrrole, Zaitsev et al have also prepared 2,3‘-analogues of bipyrrole through the intermediacy of O -vinyloxime pyrroles. The first notable observation was made during the synthesis of CC-1065, a potent antitumor and antibiotic wherein 3,3‘-bipyrrole was the building block …”