Many physiological responses to dioxin-like compounds (DLCs), including polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are mediated by the aryl-hydrocarbon receptor (AhR). In birds, activation of the AhR stimulates the transcription of cytochrome P4501A (CYP1A) genes, including CYP1A4 and CYP1A5, and ultimately leads to expression of biotransformation enzymes, including ethoxyresorufin-O-deethylase (EROD). It is well established that potencies of different DLCs range over several orders of magnitude. There is also a wide variation among birds in their responsiveness to DLCs both in efficacy and threshold for effects. A molecular basis for this differential sensitivity has been suggested. Specifically, a comparison of the AhR ligand-binding domain (LBD) indicated that key amino acid residues are predictive of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitivity. Based on sequencing of the AhR LBD from numerous avian species a sensitive classification scheme has been proposed (in order of decreasing sensitivity, chicken (type I; sensitive) > Common pheasant (type II; moderately sensitive) > Japanese quail (type III; insensitive)). A series of egg injection studies with White-leghorn chicken (<i>Gallus gallus domesticus</i>), Common pheasant (<i>Phasianus colchicus</i>) and Japanese quail (<i>Coturnix japonica</i>) were performed to determine whether molecular and biochemical markers of exposure to DLCs are predictive of the proposed classification scheme. In addition, I was interested in determining whether this classification scheme applies to other DLCs, specifically dibenzofurans. Determining which species are "chicken- like", "pheasant-like" and "quail-like" in their responses to DLCs should allow more refined risk assessments to be conducted as there would be less uncertainty about the potential effects of DLCs in those species for which population-level studies do not exist.<p> Several concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or 2,3,7,8-tetrachlorodibenzofuran (TCDF) (triolein vehicle) were injected into the air cells of Japanese quail, Common pheasant and chicken eggs. Liver from 14 d post-hatch chicks was harvested for analysis of CYP1A4 and CYP1A5 mRNA abundance by quantitative real-time PCR (Q-PCR), and EROD activity. Lowest observed effective concentration (LOEC) and relative potency (ReP) values for CYP1A mRNA abundance and EROD activity were determined and used to make comparisons of sensitivity between each species and DLC potency within each species.<p> The TCDD is widely considered to be the most potent DLC and this is supported by the rank order of LOEC values for CYP1A5 mRNA abundance in White-leghorn chicken (TCDD > PeCDF > TCDF). CYP1A4 mRNA abundance and EROD activity in White-leghorn chicken were significantly increased in the lowest dose exposure groups of each of the three DLCs, so the potency of these compounds based on these endpoints was not established. Interestingly, TCDD was not the most potent DLC in Common pheasant and Japanese quail. In Common pheasant, PeCDF is the most potent as a CYP1A4 mRNA inducer, followed by TCDD and TCDF. However, TCDF was the most potent EROD activity inducer for Common pheasant, followed by PeCDF, and then TCDD. No significant increases were found in CYP1A5 mRNA abundance in pheasant within the tested dose ranges for all the three DLCs. No significant increases in either CYP1A5 mRNA abundance or EROD activity were found in Japanese quail. In addition, PeCDF and TCDF, but not TCDD, significantly increased CYP1A4 mRNA abundance.<p> According to the predicted relative sensitivity by comparing the AhR LBD amino acid sequences, the White-leghorn chicken is more responsive to DLCs than the Common pheasant which is more responsive than the Japanese quail. By comparing the relative sensitivity calculated based on the LOEC values from my study, the sensitivity order to TCDD and TCDF support the proposed molecular based species sensitivity classification scheme (chicken > pheasant > quail), while pheasant is almost as sensitive as chicken to PeCDF ( pheasant ¡Ý chicken > quail).<p> Taken together, the data suggest that TCDD is the most potent DLC in White-leghorn chicken, but not in Common pheasant, or or Japanese quail. The data suggest that in type II avian species PeCDF may be more potent than TCDD. In addition, I found in my study that different biomarkers have different responses, which depends on species and chemicals as well. These data provide further insight into avian sensitivities to DLCs.</p>

Many physiological responses to dioxin-like compounds (DLCs), including polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are mediated by the aryl-hydrocarbon receptor (AhR). In birds, activation of the AhR stimulates the transcription of cytochrome P4501A (CYP1A) genes, including CYP1A4 and CYP1A5, and ultimately leads to expression of biotransformation enzymes, including ethoxyresorufin-O-deethylase (EROD). It is well established that potencies of different DLCs range over several orders of magnitude. There is also a wide variation among birds in their responsiveness to DLCs both in efficacy and threshold for effects. A molecular basis for this differential sensitivity has been suggested. Specifically, a comparison of the AhR ligand-binding domain (LBD) indicated that key amino acid residues are predictive of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitivity. Based on sequencing of the AhR LBD from numerous avian species a sensitive classification scheme has been proposed (in order of decreasing sensitivity, chicken (type I; sensitive) > Common pheasant (type II; moderately sensitive) > Japanese quail (type III; insensitive)). A series of egg injection studies with White-leghorn chicken (<i>Gallus gallus domesticus</i>), Common pheasant (<i>Phasianus colchicus</i>) and Japanese quail (<i>Coturnix japonica</i>) were performed to determine whether molecular and biochemical markers of exposure to DLCs are predictive of the proposed classification scheme. In addition, I was interested in determining whether this classification scheme applies to other DLCs, specifically dibenzofurans. Determining which species are "chicken- like", "pheasant-like" and "quail-like" in their responses to DLCs should allow more refined risk assessments to be conducted as there would be less uncertainty about the potential effects of DLCs in those species for which population-level studies do not exist.<p> Several concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or 2,3,7,8-tetrachlorodibenzofuran (TCDF) (triolein vehicle) were injected into the air cells of Japanese quail, Common pheasant and chicken eggs. Liver from 14 d post-hatch chicks was harvested for analysis of CYP1A4 and CYP1A5 mRNA abundance by quantitative real-time PCR (Q-PCR), and EROD activity. Lowest observed effective concentration (LOEC) and relative potency (ReP) values for CYP1A mRNA abundance and EROD activity were determined and used to make comparisons of sensitivity between each species and DLC potency within each species.<p> The TCDD is widely considered to be the most potent DLC and this is supported by the rank order of LOEC values for CYP1A5 mRNA abundance in White-leghorn chicken (TCDD > PeCDF > TCDF). CYP1A4 mRNA abundance and EROD activity in White-leghorn chicken were significantly increased in the lowest dose exposure groups of each of the three DLCs, so the potency of these compounds based on these endpoints was not established. Interestingly, TCDD was not the most potent DLC in Common pheasant and Japanese quail. In Common pheasant, PeCDF is the most potent as a CYP1A4 mRNA inducer, followed by TCDD and TCDF. However, TCDF was the most potent EROD activity inducer for Common pheasant, followed by PeCDF, and then TCDD. No significant increases were found in CYP1A5 mRNA abundance in pheasant within the tested dose ranges for all the three DLCs. No significant increases in either CYP1A5 mRNA abundance or EROD activity were found in Japanese quail. In addition, PeCDF and TCDF, but not TCDD, significantly increased CYP1A4 mRNA abundance.<p> According to the predicted relative sensitivity by comparing the AhR LBD amino acid sequences, the White-leghorn chicken is more responsive to DLCs than the Common pheasant which is more responsive than the Japanese quail. By comparing the relative sensitivity calculated based on the LOEC values from my study, the sensitivity order to TCDD and TCDF support the proposed molecular based species sensitivity classification scheme (chicken > pheasant > quail), while pheasant is almost as sensitive as chicken to PeCDF ( pheasant ¡Ý chicken > quail).<p> Taken together, the data suggest that TCDD is the most potent DLC in White-leghorn chicken, but not in Common pheasant, or or Japanese quail. The data suggest that in type II avian species PeCDF may be more potent than TCDD. In addition, I found in my study that different biomarkers have different responses, which depends on species and chemicals as well. These data provide further insight into avian sensitivities to DLCs.</p>

The production of sand can be a major issue in many young, unconsolidated sandstone formations where there is little to no cement holding the individual sand grains together. When such reservoirs are produced, quite often operators face problems with reduced well productivity and equipment failure. Because of these issues, the industry has developed numerous techniques in its effort to control formation sand production. Sand consolidation is one technology that has been studied and used since the 1940s. The theory behind sand consolidation technology is to place a liquid material which will create a grain to grain contact that will bind individual sand grains together. Most consolidation treatments contain a preflush to clean and wet the surface, the consolidating system to bind the sand grains and give residual strength, and, finally, an overflush to ensure the formation is still able to produce fluids. With the successful placement of this fluid, the sand grains will be locked in placed so that they will not be produced. The technology has gone through many phases of conception since the 1940s; however, most consolidation material that is pumped in the past has been based upon an epoxy or furan backbone. While there are many technologies available, for the purpose of my research, the epoxy technology was experimentally investigated. The testing of the fluid involved investigating numerous additives to obtain the correct residual strength of the sample, as well as the necessary retained permeability. For the epoxy fluid, the optimal preflush, epoxy system and overflush formulations were determined after 250 checkout tests. Based upon these tests, the fluid was optimized to its working time and UCS results. The optimal system included the addition of PA2 to the preflush, along with PA1 and an aromatic amine curing agent to the epoxy system. PA1 and PA2 are adhesion promoter additives which were deemed necessary as a result of the testing. This system was then tested further in a HP/HT cell. While there is still room for improvement with respect to retained permeability, the system still performs very well in terms of UCS.

In the early 1990s polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) contamination of fish was widely associated with bleached kraft pulp mills. Regulations were put into place in Canada and elsewhere to reduce or eliminate the presence of these chemicals in pulp mill effluents. The industry quickly introduced treatment and process changes such as elemental (ECF) and total chlorine free (TCF) bleaching, which resulted in dramatically reduced PCDD/F concentrations in pulp mill effluents. However, PCDD/Fs may remain a concern for the receiving environment near bleached kraft pulp mills due to their tendency to persist in sediments and bioaccumulate in aquatic biota. Several studies conducted in the early 1990s reported significantly elevated levels of PCDD/Fs in white sucker (Catostomus commersoni) exposed to bleached kraft mill effluent (BKME). Particularly high concentrations were observed in the receiving environment of two mills in northern Ontario. The first mill, located in the town of Terrace Bay, discharges effluent into Jackfish Bay, Lake Superior. The second mill is located in Smooth Rock Falls, Ontario and discharges effluent into the Mattagami River where effects have been observed in fish collected downstream of the pulp mill. Over time, both mills have undergone a number of process upgrades, including a transition to 100% chlorine dioxide (ClO2) substitution. In 2006 the Tembec Smooth Rock Falls Pulp and Paper Mill closed permanently, while the mill in Terrace Bay has gone through a number of temporary shutdowns and is currently in the process of transitioning to a dissolving pulp process. Temporal changes in PCDD/F contamination was examined in white sucker historically exposed to BKME in Jackfish Bay and the Mattagami River, following mill process changes and closures. Historical data was summarized from studies conducted in the 1990s and analyzed along with liver tissue of male white sucker collected from each location in 2011 and 2012. The body burden of each fish was analysed using Toxic Equivalency (TEQ) calculations to account for concentration and relative toxicity of 2,3,7,8??? substituted PCDD/F congeners. At Jackfish Bay, concentrations of PCDD/Fs in surface sediment and dated sediment cores were used to document the spatial and temporal pattern of PCDD/F contamination in relation to historical process upgrades and operational changes at the mill. PCDD/Fs measured in white sucker liver samples collected from Jackfish Bay during gonadal recrudescence in the fall illustrate a decrease in mean TEQ from 74.2 ?? 20.9 pg???g-1 in 1991 to 3.34 ?? 2.05 pg???g-1 in 2012. These values were slightly elevated compared to the remote reference location at Mountain Bay, Lake Superior, which exhibited a mean TEQ of 1.88 ?? 0.45 pg???g-1 and 1.06 ?? 0.69 pg???g-1 in white sucker collected in fall 2011 and 2012, respectively. Although below consumption guidelines, trace levels of PCDD/Fs persist in fish collected from Jackfish Bay and these concentrations are suspected to reflect sediment contamination in Moberly Bay (part of Jackfish Bay). A unique PCDD/F contaminant profile, dominated by 2,3,7,8??? tetrachlorodibenzo???p???dioxin (TCDD) and dibenzofuran (TCDF), was observed in white sucker and sediment collected from Jackfish Bay. Analysis of surface sediment collected throughout Jackfish Bay revealed elevated PCDD/F concentrations, compared to reference areas in Lake Superior. TEQ values measured in surface sediment from the depositional areas of Moberly Bay exceeded the Canadian Council of Ministers of the Environment (CCME) guidelines. In 1991 PCDD/F contamination, reported as mean TEQ, of white sucker collected downstream of the pulp mill outfall in Smooth Rock Falls reached levels of 111 ?? 86.2 pg???g-1. At the time, the mill utilized molecular chlorine (Cl2) in the bleaching sequence and employed primary effluent treatment. A dramatic decline was observed in PCDD/F concentrations of fish collected in 1993 and 1995, corresponding to implementation of 100% ClO2 substitution in the bleaching process. PCDD/F contamination in white sucker collected from the Mattagami River in 2011 and 2012 were similar upstream (0.53???1.49 pg TEQ???g-1) and downstream (0.75???2.87 pg TEQ???g-1) of the historical pulp mill outfall at Smooth Rock Falls, suggesting a return to background condition following the 2006 mill closure. Levels of 2,3,7,8???TCDD and 2,3,7,8???TCDF in liver tissue of fish collected downstream declined drastically compared to concentrations measured in 1991. The PCDD/F congener profile observed in white sucker downstream in 2011 and 2012 was more similar to fish collected from the reference site upstream than exposed fish collected in 1991. No sediment depositional areas suitable for taking a core sample were found on the river downstream of Smooth Rock Falls due to the nature of the system. This study supports the conclusion that particulate (POM) and dissolved organic matter (DOM) from continuous inputs of effluent were likely the primary source of PCDD/Fs to fish in these receiving environments, with only a small contribution from surface sediment. Results indicate a decreasing trend in PCDD/F contamination of white sucker historically exposed to bleached kraft pulp mill effluent in the receiving environments of Jackfish Bay and the Mattagami River, consistent with mill process upgrades to eliminate the use of elemental chlorine from the bleaching sequence. Current levels of PCDD/Fs measured in white sucker collected from these locations suggest a return to background condition.

No description available.

Furan wird in einer Vielzahl von Speisen durch Hitzebehandlung gebildet und ist kanzerogen in der Leber von Ratte und Maus. Durch die hohe Flüchtigkeit von Furan ist eine Expositionsabschätzung auf Basis der Kontamination von Lebensmitteln nur bedingt möglich. Ein alternativer Ansatz dazu ist die Identifizierung von Furanmetaboliten als Expositions­biomarker. Nach der Aufnahme wird Furan zunächst zum Dialdehyd cis-2-Buten-1,4-dial oxidiert. cis-2-Buten-1,4-dial besitzt mehrere elektrophile Strukturelemente, welche eine Reaktion mit Protein und DNS wahrscheinlich machen und damit zur bekannten Toxizität von Furan beitragen können. Es stellt sich in diesem Zusammenhang die Frage, ob eine Reaktion mit Protein die Reaktion mit der DNS verhindern kann und somit keine direkt gentoxischen Effekte auftreten. Für ein kanzerogenes Agens ohne direkte gentoxische Wirkung kann eine Schwellendosis unterhalb derer kein DNS-Schaden auftritt diskutiert werden. Für eine fundierte Risikobewertung bezüglich der Aufnahme von Furan über die Nahrung ist dies unabdingbar. In der vorliegenden Arbeit wurde nach der oralen Gabe von Furan im Urin von Fischer 344 Ratten nach Metaboliten gesucht. Eine Kontrollgruppe erhielt nur die Trägersubstanz Öl. Das vor und nach Exposition über jeweils zwei 24 Stunden Perioden gesammelte Urin wurde mittels einer Tandemmassenspektrometrie-Methode analysiert. Die Methode bestand aus einem Full-Scan und einer darüber gesteuerten Aufzeichnung eines Fragmentionenspektrums. Die Full-Scan-Daten wurden mit Hilfe der Hauptkomponentenanalyse untersucht. In der ersten Sammelperiode nach der Behandlung konnten durch die erste Hauptkomponente die behandelten von den unbehandelten Tieren getrennt werden. Aus den für die Trennung relevanten Verbindungen konnten fünf Biomarker strukturell aufgeklärt werden. In einer weiteren Tierstudie an Ratten und Mäusen wurde die Kinetik und die Dosis-Wirkungs-Beziehung der identifizierten Biomarker untersucht. Die gezielte LC-MS/MS-Analyse der Urine auf die identifizierten Biomarker hin zeigte, dass in der Ratte alle und in der Maus alle bis auf einen dosisabhängig anstiegen. Die Kinetik der Ausscheidung lieferte wertvolle Hinweise auf die Entstehung der Biomarker. Die Ausscheidung der Biomarker mit Lysinstruktur erfolgte über mehr als 72 Stunden. Dies war ein Hinweis auf eine Freisetzung aus Protein. Die Ausscheidung der restlichen Verbindungen erfolgte ausschließlich in den ersten 24 Stunden. Die in der Literatur vorhandenen Daten zur Gentoxizität von Furan und cis-Buten-1,4-dial sind unschlüssig und unvollständig. In der vorliegenden Arbeit wurde cis-2-Buten-1,4-dial im Ames Stamm TA104 und in L5178Y Mauslymphomzellen auf Mutagenität und Gentoxizität untersucht. Durch starke Zytotoxizität war der Konzentrationsbereich auf 4.5 µmol/Platte limitiert. Innerhalb dieses Bereich konnte mit der Vorinkubationsvariante des Ames-Tests keine Mutagenität beobachtet werden. Die L5178Y Mauslymphomzellen wurden mit Standardprotokollen für den Mikrokern-Test, Kometen-Test und den Thymidinkinase-Test untersucht. Der Konzentrationsbereich von cis-2-Buten-1,4-dial erstreckte sich bis 100 µM, konnte aber auf Grund der starken Zytotoxizität nur bis 25 µM ausgewertet werden. Dennoch konnte bereits in diesem Bereich ein 1.7- bzw. 2.2-facher Anstieg im Kometen- bzw. Thymidinkinase-Test beobachtet werden. Verglichen mit der Positivkontrolle Methylmethansulfonat hatte cis-2-Buten-1,4-dial bei einer deutlich höheren Zytotoxizität eine ähnliche Potenz bezüglich der Mutagenität und Gentoxizität. Um das DNS-vernetzende Potential von cis-2-Buten-1,4-dial zu bestimmen wurde eine Variante des Kometen-Tests verwendet. Es wurde dabei untersucht, ob die Vorbehandlung von Zellen mit cis-2-Buten-1,4-dial die durch &#947;-Strahlung induzierbaren Kometen reduzieren kann. Während die Positivkontrolle Glutaraldehyd die Kometen tatsächlich verringerte, blieb dieser Effekt bei cis-2-Buten-1,4-dial aus. Im Gegenteil, bei einer Konzentration von &#8805;100 mM konnte durch die Zunahme von Zellen mit beginnender Apoptose ein Anstieg der Kometen beobachtet werden. Obwohl cis-2-Buten-1,4-dial sehr deutliche gentoxische und mutagene Effekte zeigte, beschränkte die hohe Zytotoxizität den auswertbaren Bereich. Möglicherweise kann diese Problematik einen Teil der unschlüssigen Ergebnisse erklären, sicher ist jedoch, dass für die Untersuchung der Mechanismen der Toxizität und Kanzerogenität ein Beitrag von nicht gentoxischen Effekten diskutiert werden muss. / Furan has been found in a number of heated food items and is carcinogenic in the liver of rats and mice. Estimates of human exposure on the basis of concentrations measured in food are not reliable because of the volatility of furan. A biomarker approach was therefore indicated. Metabolism of furan includes the formation of an unsaturated dialdehyde, cis-2-butene-1,4-dial. In view of the multifunctional electrophilic reactivity of cis-2-butene-1,4-dial, adduct formation with protein and DNA may explain some of the toxic effects. DNA-adduction is a direct genotoxic effect. The major question was weather a direct genotoxicity of cis-2-butene-1,4-dial could be prevented by the reaction with protein structures. If so, the genotoxic and mutagenic effects are likely to show a threshold dose, reducing the cancer risk for low exposure levels. We searched for metabolites excreted in the urine of male Fischer 344 rats treated by oral gavage with 40 mg furan per kg body weight. A control group received the vehicle oil only. Urine collected over two 24-hour periods both before and after treatment was analyzed by a column-switching LC-MS/MS method. Data were acquired by a full scan survey scan in combination with information dependent acquisition of fragmentation spectra by the use of a linear ion trap. The full scan data was analyzed by principal component analysis (PCA). The first principal component fully separated the samples of treated rats from the controls in the first post-treatment sampling period. Five of the compounds that are responsible for the separation could be identified as the reaction product of cis-2-butene-1,4-dial with either glutathion or lysine (protein). In a second animal study rats and mice were treated with seven different doses of furan in the range from 125 µg to 8 mg per kg body weight. Dose-response and kinetic over 72 h of the seven identified biomarkers was examined by LC-MS/MS in the urine. In the rats all biomarkers showed a dose-dependent increase. In the mice one biomarker lacked of dose dependency. Different excretion profiles were attributed to the formation of either protein adducts or glutathione conjugates. Whereas the protein-derived biomarkers with a lysin moiety showed a slow excretion over more than 72 h, the glutathion-dervived biomarkers were only excreted within the first 24 h. Short-term tests for genotoxicity of furan in mammalian cells are inconclusive, little is known for cis-2-butene-1,4-dial. We investigated cis-2-butene-1,4-dial generated by hydrolysis of 2,5-diacetoxy-2,5-dihydrofuran for genotoxicity and mutagenicity in Salmonella typhimurium (Strain TA104) and in L5178Y mouse lymphoma cells. The Ames Test was negative in the preincubation assay with and without reduction of cytotoxicity by addition of glutathione after preincubation phase. Remarkable cytotoxicity limited the analysis range up to 4.5 µmol/plate. Mutagenicity and genotoxicicty in L5178Y mouse lymphoma cells was evaluated using standard procedures for the comet assay, the micronucleus test, and the mouse lymphoma thymidine kinase gene mutation assay. cis-2-butene-1,4-dial was tested at 0, 6.25, 12.5, 25, 50, and 100 µM. Cytotoxicity was remarkable; cell viability at 50 µM was reduced to <50%. Up to 25 µM, cell viability was >90%, and measures of comet assay and thymidine kinase mutations were increased over control about 1.7 an 2.2-fold, respectively. Compared to methyl methanesulfonate used as positive control, cis-2-butene-1,4-dial was of similar potency for genotoxicity but much more cytotoxic. A potential cross-linking activity of cis-2-butene-1,4-dial was investigated by checking whether gamma radiation-induced DNA migration in the comet assay could be reduced by pretreatment with cis-2-butene-1,4-dial. As opposed to the effect of the positive control glutaraldehyde, cis-2-butene-1,4-dial treatment did not reduce the comets. On the contrary, an increase was observed at &#8805;100 µM cis-2-butene-1,4-dial, which was attributable to early apoptotic cells. Although cis-2-butene-1,4-dial was found to be a relatively potent genotoxic agent in terms of the concentration necessary to double the background measures, cytotoxicity strongly limited the concentration range that produced interpretable results. This may explain some of the inconclusive results and indicates that nongenotoxic effects must be taken into account in the discussion of modes of toxic and carcinogenic action of furan.

This thesis describes the chemistry developed during a study of novel transition metal-catalysed reactions. Chapter 2 describes a novel procedure for the synthesis of 2,5-disubstituted furans via the isomerisation of 1,4-alkyne diols, avoiding the pitfalls of the traditional Paal-Knorr reaction. The initial ruthenium catalysed isomerisation is followed by an in situ cyclocondensation reaction using an acid co-catalyst in a one step route to furan derivatives. In addition the synthesis of the 1,4-dicarbonyl surrogates, 1,4-alkyne diols, is detailed. The methodology detailed in chapter 2 is then used in the synthesis of pyrrole derivatives in Chapter 3. Replacement of the acid co-catalyst with 2 equivalents of amine allow various pyrrole derivatives to be synthesised using the 1,4-alkynediols as starting materials. Various amines can also be used from anilines, benzylamines and aliphatic amines, allowing access to a wide range of products.

¤@¡BPyrolysis of 2-azido-1-(4-methoxyphenyl)ethanone (69) and 2-(2-azidoethyl)furan (85) gave nitrene intermediate to study. There is 2-(4-methoxybenzoyl)-4-(4- methoxyphenyl)imidazole (81) ¡B2-(4-methoxybenzoyl)-5-(4-methoxyphenyl) imidazole] (81¡¦)¡B2,3-di(4-methoxybenzoyl)-5-(4-methoxyphenyl) pyrazine] (82) and 3,5-di(2-furyl) pyridine (92) for pyrolysis products. ¤G¡BPyrolysis of3-methyl-2-cyclohexen[b] furylmethyl benzoate) (50) gave carbene intermediate to study. There is 2,3-dimethylene cyclohexen[b]furan (59) for pyrolysis products.

1. 2-[2-(2vinylphenyl)ethenyl]thiophene ( 30 ) and 2,2-(o-phenylenedivinylene)dithiophene ( 31 ) were studied under pyrolytic and photolytic conditions, photolytic of 30 gave upon bicyclic product 35, whereas photolytic of 31 gave products 37 and 39, FVP of 30 and 31 gave 34 and 37, respectively,which all include naphthalene nucleus. 2. 2-methoxystilbene ( 17 ) and 3-methoxystilbene ( 18 ) were studied under pyrolytic conditions, FVP of 17 gave single product 2-Phenylbenzo[b]furan ( 23 ), FVP of 18 gave 2-phenanthrol ( 27 ), ( 4-phenanthrol ) ( 28 ), trans-3- hydroxystilbene ( 29 ), Fluoren 9 -one ( 30 ) and a pair of isomer 1H-benz[e]indene ( 11a ) and 3H-benz[e]indene (11b).

1.trans o-methoxystilbene and its derivatives 47a-f had been studied by means of pyrolysis and photolysis. Under pyrolytic conditions, compounds 47a-f gave not only the expected products 52a,c-f, but also their corresponding isomers 53a,c-f . Furthermore, compound 47b gave naphthalene (63) as the major product by opening the furan ring at higher temperature. Under photolytic conditions, compounds 47a-f gave the expected photocyclic products 2a-f and 109a-f.2.Pyrolytic chemistry of N-(N-Methyl-3-indolyl)methyl benzamide (45) hes been studied. Pyrolysis of 45 gave 3-methyl quinoline (38), 4-methyl quinoline (39) and secondary pyrolysis product quinoline (36). 2.Pyrolytic chemistry of N-(N-Methyl-3-indolyl)methyl benzamide (45) hes been studied. Pyrolysis of 45 gave 3-methyl quinoline (38), 4-methyl quinoline (39) and secondary pyrolysis product quinoline (36).