91587-24-5Relevant academic research and scientific papers
Intervention of carbonyl and oxonium ylides in reactions of [(alkoxycarbonyl)phenyl]carbenes in the gas phase forming 3-alkylphthalides and 2-alkoxy-1(2H)-benzocyclobutenone. 13C and 18O labeling studies
Tomioka, Hideo,Kobayashi, Noriyuki,Murata, Shigeru,Ohtawa, Yasuki
, p. 8771 - 8778 (2007/10/02)
The generation of isomeric [(methoxycarbonyl)phenyl]carbenes (6a-c) by flash vacuum pyrolysis (FVP, 350-450 C, 10-5 Torr) of the corresponding diazomethanes (1a-c) produced 3-methylphthalide (2) and 2-methoxy-l(2H)-benzocyclobutenone (3), presumably as a result of carbene-carbene rearrangement followed by the interaction of the methoxycarbonyl group with the carbene center in the ortho isomer (6a). Labeling studies were carried out in order to determine the mechanism of the reaction. Thus, FVP of [o-(carboxy-13C](methoxycarbonyl)phenyl]diazomethane produced 3-methyl[carbonyl-13C]phthalide and 2-methoxy-1(2H)-[carbonyl-13C]benzocyclobutenone, thereby indicating that 3 was formed via Stevens-type migration of the acyl group in an oxonium ylide intermediate (9). FVP of [p-[carfronyl-18O](methoxycarbonyl)phenyl]diazomethane, on the other hand, produced 3-methyl[ether-18O]phthalide, along with a small amount of 3-methyl[carbonyl-18O]phthalide and 3-methoxy-1(2W)-[carbonyl-18O]benzocyclobutenone, indicating that 2 was produced mainly via 1,5-methyl migration in a carbonyl ylide intermediate (7). Generation of other [(alkoxycarbonyl)phenyl]diazomethanes (16, where alkoxy = EtO and PriO) under similar conditions also produced 3-alkylphthalides (17) and 2-alkoxybenzocyclobutenones (18), but phthalide 19, which was not detected in the FVP of 1, was also formed in this case, presumably as a result of α,β-elimination of alkenes in the oxonium ylide. These results showing the intervention of the oxonium ylide of the ester group are in marked contrast to the observation that, at much lower temperatures in the liquid and solid phases, only the carbonyl ylide has been involved.
Conformationally Restricted Retinoids
Dawson, Marcia I.,Hobbs, Peter D.,Derdzinski, Krzysztof,Chan, Rebecca L.-S.,Gruber, John,et al.
, p. 1516 - 1531 (2007/10/02)
A series of conformationally restricted retinoids was synthesized and screened in two assays used to measure the ability of retinoids to control cell differentiation, namely, the reversal of keratinization in tracheal organ culture from vitamin A deficient hamsters and the inhibition of the induction of mouse epidermal ornithine decarboxylase by a tumor promoter.These compounds had bonds corresponding to selected bonds of the E-tetraene chain of retinoic acid (1) held in a planar cisoid conformation by inclusion in an aromatic ring.The meta-substituted analogue 3 of 4-benzoic acid (2) was far less active than 2 in both assays.In contrast, the vinyl homologue of 2 (4) and the 7,8-dihydro and 7,8-methano analogues (5 and 6) had activity comparable to that of 2.Analogues of 4-benzoic acid (7) were also screened.Replacement of the tetrahydronaphthalene ring of 7 by a benzonorbornenyl group (9) significantly reduced activity, as did removal of the vinylic methyl group from 9 (10).Replacement of the propenyl group of 9 by a cyclopropane ring (12) also reduced activity.Replacement of the tetrahydronaphthalene ring of 7 by 4,4-dimethyl-3,4-dihydro-2H-1-benzopyran and -benzothiopyran rings (13 and 14) also decreased activity.Inclusion of the 7,9 double bond system of 1 in an aromatic ring (15 and 16) reduced activity, whereas inclusion of the 5,7 double bond system in an aromatic ring enhanced activity (7 and 19).Inclusion of the 11,13 and 9,11,13 double bond systems in aromatic rings (2 and 18) also reduced activity below that of 1.Retinoic acid, 7, 13, 14, and 19 inhibited papilloma tumor formation in mice.Toxicity testing indicated that 7 was more toxic than 1, 13, 14, and 19, 19 was more toxic than 1, and 13 and 14 were less toxic than 1.
