Flash vacuum pyrolysis (FVP) of indol-1-ylacrylate derivatives 11 and 15 or the isomeric indol-3-ylacrylates 21, 22, and 24 at 925 degrees C (0.05 Torr) provides pyrrolo[1,2-a]indol-3-ones 2, 18, 28, and 29 in 53-90% yield by a cascade mechanism that involves a sigmatropic migration, elimination, electrocyclization sequence. Pyrrolo[1,2-a]imidazol-5-ones 3 and pyrrolo[1,2-c]imidazol-5-ones 4 were similarly obtained by FVP of corresponding 2,5-unsubstituted imidazol-1-ylacrylates (e.g., 33), with the former isomer predominating in ca. 80:20 ratio. Migration to the 2-position is therefore favored in the initial sigmatropic shift. FVP of 2-substituted imidazol-1-ylacrylates 35, 37, and 51 (825-875 degrees C) instead give pyrrolo[1,2-c]imidazol-5-ones 56-58 only (88-91%), and that of 4,5-disubstituted imidazol-1-ylacrylates 39 and 41 (825-850 degrees C) provide pyrrolo[1,2-a]imidazol-5-ones 59 and 60 exclusively (93-95%), and thus the selectivity of the initial shift can be controlled by the presence of substituents on the imidazole 2- and 5-positions. FVP of the benzimidazole analogues 61 and 62 at 950 degrees C gave the pyrrolo[1,2-a]benzimidazol-1-ones 6 (71%) and 63 (36%), respectively.
Flash vacuum pyrolysis (FVP) of the pyrrolylcinnamate derivative 3 gives the pyrrolo[1,2-a]quinoline 10, the pyrrolo[2,1-a]isoindole 13 (R = Me) and the benzindoles 14 and 15, all in low yield, whose structures were determined by NMR methods. The isomeric precursor 4 cyclises efficiently under the same conditions to give the pyrrolizin-3-one 16.
Isoindolo[2,1-a]indol-6-one 1 is formed by a sigmatropic shift-elimination-cyclisation cascade by flash vacuum pyrolysis (FVP) of methyl 2-(indol-1-yl)benzoate 7 at 950 degrees C. The dihydro compound 16 is easily obtained by catalytic reduction of 1, but the reaction is very sensitive to steric effects at the 11-position. Attempted ring-opening of 1 in basic methanol provides an equilibrium of isoindolo[2,1-a]indol-6-one 1 and the ester 19. Lithium aluminium hydride reduction of 1 provides the alcohol 22 which can be dehydrated to a mixture of 23 and 24 by FVP at 800-950 degrees C.
Z)-Urocanic acid and its derivatives can be made stereospecifically by ring-opening of pyrrolo [1,2-c]imidazol-5-ones in aqueous tetrahydrofuran.(E)-Urocanic acid [(E)-1] is a major chemical component of the epidermis, formed from histidine by the enzyme histidase in the stratum corneum. 1 Upon ultraviolet irradiation of the skin, trans-urocanic acid [(E)-1] isomerizes to the cis-form (Z)-1, which is of current biomedical 2 and photophysical 3 interest (Scheme 1). In particular, (Z)-urocanic acid [(Z)-1] is known to have an immunosuppressive effect in vivo or in vitro and its mode of action has been recently investigated. 4Photoisomerization of the commercially available E-isomer (E)-1 5 or its methyl ester (E)-2 6 are the only known routes to Z-urocanic acid [(Z)-1]. A photostationary equilibrium between the two isomers is attained (at which the conversion reaches 70%) and so a chromatographic separation is necessary. 5,7 Relatively few derivatives of urocanic acids have been synthesized, especially as Z-isomers, though fluorinated analogues provide an interesting exception. 8In this paper, we report a new, stereospecific route to (Z)-urocanic acid [(Z)-1] and its derivatives, by ring-opening of the pyrrolo[1,2-c]imidazol-5-one (azapyrrolizinone 9-12 ) system 4. These heterocycles are best made by flash vacuum pyrolysis (FVP) of (imidazol-4-yl)acrylate esters 2, by an isomerization-elimination-electrocyclization sequence 10 or by FVP of 2-substituted (imidazol-1-yl)acrylate esters 3, in which directed sigmatropic migration of the 1-substituent precedes the elimination and cyclization steps (Scheme 2). 11,12 Few reactions of azapyrrolizinones have been published. However, pyrrolizin-3-ones themselves are readily ringopened by treatment with hard nucleophiles 7,13 and the aza-analogues, which have an imidazole unit as a formal leaving group, would be expected to show greater reactivity.In practice, heating 4a-c in aqueous THF (in the absence of any acidic or basic reagents) for three hours provided (Z)-urocanic acid [(Z)-1] and its analogues (Z)-5a,b in high yields (Scheme 3). The progress of the reaction could be monitored by the disappearance of the characteristic yellow color of the azapyrrolizinones. For the preparation of (Z)-1, it is particularly important to minimize decomposition of the azapyrrolizinone 4c by adding the THF-water mixture directly to the azapyrrolizinone in the FVP cold finger trap and carrying out the hydrolysis immediately after the pyrolysis step. Isolation and manipulation of the azapyrrolizinone 4c can cause decomposition.After the hydrolysis step, the products were isolated simply by removal of the solvents without the need for chromatography. In this way, the Z-urocanic acid [(Z)-1] and its derivatives (Z)-5a,b were obtained in 72-89% overall yields based on the pyrolysis precursor. The Z-configuration of the alkene unit of (Z)-1 and (Z)-5a was clear from their NMR spectra ( 3 J = 12.5-13.0 Hz) and in the case of (Z)-5b by a NOESY experiment. No isomerization of the alkene took place...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.