Flavio Cermola

Determination of photostability and photodegradation products of indomethacin in aqueous media

Photochemical behaviour of indomethacin in aqueous media at 254nm, 310nm and sunlight was studied by HPLC. The drug exhibited a similar behaviour in all the irradiation experiments affording eight photoproducts that were separated and identified. The main photochemical routes are suggested to proceed via decarboxylation, followed by oxygenation to give an alcohol and an aldehyde and/or by solvent trapping to produce the alcohol. Photoinduced hydrolysis of CO-N bond and oxidative C2-C3 bond breakage also occur.

The first nucleophilic aromatic substitution of suitably activated 2-methoxyfurans with grignard reagents

Abstract The reaction of 2-methoxyfuroates 1 with Grignard reagents 2 leads to tertiary alcohols or SNAr products depending on the position of the alkoxycarbonyl group. OMe-Displacement occurs only for 3-substituted derivatives. It takes place even for 3-acetyl-2-methoxyfuran while the presence of a further ester function at 4 position induces the formation of the sole 4-tertiary alcohol. The OMe-substitution has been verified for a wide range of furans and Grignard reagents and low yields have been found only in the reactions with the benzylic and allylic reagents which are delocalized anions. A mechanistic interpretation is given.

Effects of sensitizers on the photodegradation of the systemic fungicide triadimenol.

The photochemical behaviour of triadimenol (1) under various conditions has been examined. Significant degradation is obtained only in the presence of electron-acceptor sensitizers as 9,10-dicyanoanthracene or 2,4,6-triphenylpyrylium tetrafluoroborate, and long irradiation times are required. 1H-1,2,4-Triazole (2), 4-chlorophenyl formate (3), 4-chlorophenol (4), 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one (5), 4-chlorophenyl 2,2-dimethylpropanoate (6) and 4-chlorobenzoic acid (7) were identified as photoproducts by NMR and GC-MS.

Photochemical fate and eco-genotoxicity assessment of the drug etodolac

The photochemical behavior of etodolac was investigated under various irradiation conditions. Kinetic data were obtained after irradiation of 10(-4) M aqueous solutions by UVB, UVA and direct exposure to sunlight. The Xenon lamp irradiation was used in order to determine the photodegradation quantum yield under sun-simulated condition (ϕsun). The value was determined to be=0.10±0.01. In order to obtain photoproducts and for mechanistic purposes, experiments were carried out on more concentrated solutions by exposure to sunlight and to UVA and UVB lamps. The drug underwent photooxidative processes following an initial oxygen addition to the double bond of the five membered ring and was mainly converted into a spiro compound and a macrolactam. Ecotoxicity tests were performed on etodolac, its photostable spiro derivative and its sunlight irradiation mixture on two different aquatic trophic levels, plants (algae) and invertebrates (rotifers and crustaceans). Mutagenesis and genotoxicity were detected on bacterial strains. The results showed that only etodolac had long term effects on rotifers although at concentrations far from environmental detection values. A mutagenic and genotoxic potential was found for its derivative.

Sensitized photooxygenation of the fungicide furalaxyl

BackgroundThe photolysis of pesticides is of high current interest since light is one of the most important abiotic factors which are responsible for the environmental fate of these substances and may induce their conversion into noxious products. The action of light can also be mediated by oxygen and synthetic or naturally occurring substances which act as sensitizers. Our objective in this study was to investigate the photochemical behaviour of the systemic fungicide furalaxyl in the presence of oxygen and various sensitizers, and to compare the toxicity of the main photoproduct(s) to that of the parent compound. Previous reports on the direct potolysis of the pesticide demonstrated a very slow degradation and the only identified photoproducts were N-2,6-xylyl-D,L-alaninate and 2,6-dimethylaniline.MethodsSolutions of furalaxyl in CH3CN were photooxygenated using a 500W high-pressure mercury lamp (through a Pyrex glass filter, »>300 nm) or a 650W halogen lamp or sunlight and the proper sensitizer. When sunlight was used, aqueous solutions were employed. The photodegradation was checked by NMR and/or GC-MS. The photoproducts were spectroscopically evidenced and, when possible, isolated chromatographically. Acute toxicity tests were performed on the rotifer Brachionus calyciflorus, the crustacean cladoceran Daphnia magna and the anostracan Thamnocephalus platyurus, while chronic toxiciry tests (sublethal endpoints) comprised a producer, the alga Pseudokirchneriella subcapitata and the crustacean Ceriodaphnia dubia, as a consumer.Results and DiscussionIn the presence of both oxygen and sensitizer, furalaxyl underwent rapid photochemical transformations mainly to N-disubstituted formamide, maleic anhydride and a 2(5H)-furanone derivative. The formation of these products was rationalized in terms of a furan endoperoxide intermediate derived from the reaction of furalaxyl with active dioxygenated species (singlet oxygen, superoxide anion or ground state oxygen). The 2(5H)-furanone exhibited a higher toxicity than the parent compound.ConclusionThis work reports the first data on the photosensitized oxygenation of furalaxyl with evidence of the high tendency of the pesticide to undergo photodegradation under these conditions leading, among other things, to a 2(5H)-furanone, which is more toxic than the starting furalaxyl towards aquatic organisms.Recommendations and OutlookInvestigation highlights that the photolytic fate of a pesticide, although quite stable to direct photoreaction due to its low absorption of solar radiation at ground level, can be significantly influenced in the environment by the presence of substances with energy or electron-transfer properties as natural dyes, e.g. chlorophyll, or synthetic pollutants, e.g. polycyclic aromatic hydrocarbons (PAH).

Bromination and iodination of donor-acceptor cyclopropanes. Evidence for an ET mechanism

Abstract Ethyl 2,2-dimethoxycyclopropanecarboxylates 1a – d react easily with Br 2 and I 2 in CCl 4 or CH 2 Cl 2 leading, in high yields, to 1-ethyl-4-methyl 2-halobutanedioates 2 and 3 , respectively. Bromination in the presence of pyridine, NBS, trimethyl phosphate, and iodination with ICl and ICl/pyridine has been also performed. A common SET mechanism may be proposed for both halogenations; depending on the reaction conditions, bromination can also occur via acid-catalysed or S E 2 routes. The reaction of the 2-ethoxyanalogues cis - 12 and trans - 12 with the same halogens proceeds in a similar manner, giving 3-formyl-2-haloesters along with the corresponding diethylacetals as main products. Iodination of 12 with the catalytic system NaI/ m -CPBA/18-crown-6 has also been investigated.

Photooxygenation of furans in water and ionic liquid solutions

Photooxygenation of differently functionalized furans is investigated in aqueous solutions and in ionic liquids [emim]Br and [bmim]BF4. The reaction is generally selective and the final products derive from rearrangement of the intermediate endoperoxides, depending mainly on the polarity and/or nucleophilic nature of the solvent.

A further selective pathway in thermal conversion of 2,5-epidioxy-2-alkoxy-2,5-dihydrofurans (2-alkoxyfuran endo-peroxides). Synthesis of the first 5-hydroperoxyfuran-2(5H)-ones

Thermal conversion of the epidioxydihydrofurans 1 leads, via dioxetanes 3, to the stereoisomeric dimers 4 which have a structural relationship with antitumour cyclic peroxides and represent convenient starting materials for several multifunctional compounds; their mild acid hydrolysis provides a convenient entry to the synthesis of the furanone derivatives 7 and 8 which are structurally related to biologically active products.

Ring-opening reactions of cyclopropanes. Part 8.1 Nitrosation of donor-acceptor cyclopropanes

The reaction of 2,2-dialkoxycyclopropane-1-carboxylates 1a–d and monoalkoxycyclopropane 1e with NOCl gives isoxazoline- and/or isoxazole-3-carboxylates by regioselective ring-opening at C1–C2 bond. A mechanistic interpretation suggests the intermediacy of well-stabilised dipolar species.

Photochemical behaviour of the systemic fungicide carboxin

Irradiation of carboxin (1) with a 500 W UV lamp (filter Pyrex) in CH3CN leads to the products 3, 5-8, 12-14 depending upon the reaction conditions. All photo-products were isolated and characterized. Photooxidation occurred even if unsensitized, while photoalteration was very slow in the absence of oxygen. The main oxygenated-products 3 and 13 were also recovered under biomimetic conditions by exposure of an aqueous solution of 1 to sunlight.