Vilsmeier Reaction of Enaminones: Efficient Synthesis of Halogenated Pyridin-2(1H)-ones

A facile and efficient one-pot synthesis of halogenated pyridin-2(1H)-ones from a series of readily available enaminones under Vilsmeier conditions is described, and a mechanism involving sequential halogenation, formylation, and intramolecular nucleophilic cyclization is proposed.

A Facile and Efficient One-Pot Synthesis of Substituted Quinolines from alpha-Arylamino Ketones Under Vilsmeier Conditions

An efficient one-pot synthesis of substituted quinolines from alpha-arylamino ketones in the presence of PBr3 in DMF has been developed. This general protocol provides a novel and facile access to substituted quinolines by sequential Vilsmeier-Haack reaction, intramolecular cyclization and aromatization reactions of alpha-arylamino ketones. PBr3 plays a dual role in the quinoline synthesis: as a key component of the Vilsmeier reagent (PBr3/DMF) and as a reducing reagent.

Vilsmeier-Haack reactions of 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans toward the synthesis of highly substituted pyridin-2(1H)-ones

A facile and efficient one-pot synthesis of highly substituted pyridin-2(IH)-ones was developed via Vilsmeier-Haack reactions of readily available enaminones, 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.

Thia-michael addition reactions in water using 3-[Bis(alkylthio) methylene]pentane-2,4-diones as odorless and efficient thiol equivalents

3-[Bis(ethylthio)methylene]pentane-2,4-dione (1a) and 3-[bis(benzylthio)methylene]pentane-2,4-dione (1b) have been investigated as non-thiolic and odorless thiol equivalents in thia-Michael addition reactions. In the presence of aqueous p-dodecyl benzenesulfonic acid (DBSA), compound (1) was cleaved and the generated thiols underwent facile conjugate addition to alpha,beta-unsaturated ketones 2 in-situ, affording the corresponding beta-keto sulfides (3) in good yields.

Synthesis and applications of 3-[6-(hydroxymethyl)pyridin-2-yl]-1,1 '-bi-2-naphthols or 3,3 '-bis[6-(hydroxymethyl)pyridin-2-yl]-1,1 '-bi-2-naphthols

A series of new 1,1'-bi-2-naphthol (BINOL) derived ligands, 3-[6-(hydroxymethyl)pyridin-2-yl]-BINOLs or 3,3'-bis[6(hydroxymethyl)pyridin-2-yl]-BINOLs, bearing one or two chiral pyridinylmetlianols attached to a binaphthyl skeleton, have been synthesized using the Suzuki cross-coupling reaction. The resulting compounds have been used as ligands in the enantioselective addition of diethylzinc to aldehydes; the products were obtained with up to 96% ee.

Addition reaction of nitrones on the reconstructed Si(100)-2 x 1 surface

The reaction of nitrone, N-methyl nitrone, and their hydroxylamine tautomers (vinyl-hydroxylamine and N-methyl vinyl-hydroxylamine) on the reconstructed Si(100)-2 x 1 surface has been investigated by means of hybrid density functional theory (B3LYP) and Moller-Plesset second-order perturbation (MP2) methods. The calculations predicted that both of the nitrones should react with the surface dimer via facile concerted 1,3-dipolar cycloaddition leading to 5-member-ring compounds. The reaction of hydroxylamine tautomers on the Si(100) surface follows pi-complex (intermediate) mechanism. For the reaction of N-methyl vinyl-hydroxylamine, the pi-complex intermediate undergoes [2+2] cycloaddition leading to a 4-member-ring compound. But in the reaction of vinyl-hydroxylamine, the intermediate undergoes H-migration reaction ("ene" reaction) resulting in the oxime-terminated Si surface. All the surface reactions result in the hydroxyl-terminated silicon surfaces, which are very useful for the further modification of the semiconductor.

Synthesis and reactivity of alpha-thio-beta-chloroacrylamides and alpha-thio-beta-chloroenones

Development of novel synthetic methodology for selective transformation of organic compounds is a central element underpinning organic synthesis with control of chemo-, regio- and stereoselectivity a very high priority. Reactions which can be conducted under mild reaction conditions and, ideally in an environmentally attractive manner, are particularly advantageous. The principal objective of this thesis was to explore the synthesis, reactivity and synthetic utility of a series of α,β-thio-β-chloroenones. The stereochemical features of these transformations and the potential of this novel series of compounds in the synthesis of bioactive compounds were of particular interest. In exploring the reactivity of these compounds, the key transformations included nucleophilic additions and Stille cross-coupling at the β-carbon. Chapter 1 reviews the literature relevant to the research conducted, and focuses in particular on the synthesis of β-chloroenones and related unsaturated carbonyl compounds. The synthesis of chalcone compounds from various precursors is also discussed, with particular emphasis on the use of palladium cross-coupling reactions in the preparation of these compounds. The biological activity of chalcones is also summarised in this chapter. The second chapter delineates the stereoselective synthesis of the novel α-thio-β-chloroenones from the corresponding α-thioketones in a multistep reaction cascade initiated by a NCS-mediated chlorination. A range of both alkyl and aryl β-chloroenones were prepared in this work and the oxidation of these compounds to the corresponding sulfoxides and sulfones is also outlined. The electrophilicity of the β-carbon of the enones was examined in nucleophilic addition/substitution reactions with successful access to a variety of synthetically useful novel adducts including acetals and enaminoketones. Investigation of the synthetic potential of the Stille cross-coupling reaction with the novel α-thio-β-chloroenones was explored and provided an efficient route for the synthesis of a novel series of chalcones. Most importantly this new methodology provided a new and synthetically powerful approach for carbon-carbon bond formation at the β-carbon under mild neutral conditions. A preliminary investigation into the use of these β-chloroenones as dienophiles in Diels-Alder cycloaddition reactions is also discussed in this chapter. Chapter 2 also reports the nucleophilic addition of N, O, S and C nucleophiles to previously described β-chloroacrylamides and their corresponding sulfoxide derivatives. This work builds on previous research carried out in this programme and the reactivity of these β-chloroacrylamides at the sulfide and sulfoxide level is compared. Comparison of the reactivity of the β-chloroacrylamides, in nucleophilic substitution and Stille-coupling, with that of the novel β-chloroenones is of interest. Finally, the biological activity of both the β-chloroenones and the β-chloroacrylamides in terms of cytotoxicity is summarised in Chapter 2. The final chapter, Chapter 3, details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research.

Photoelectrochemistry with quinone radical anions: Kinetics of homogeneous redox catalysis

Cyclic voltammograms of quinones were recorded in acetonitrile in the presence of various substrates: carbonyl compounds, halobenzenes, Methyl Viologen and Neutral Red. When illuminated with light of λ >410 nm, catalytic waves were observed. From the ratio of the catalysed to uncatalysed peak current, electron transfer rate constants were calculated using the working curves of Saveant and coworkers. The values of these rate constants were compared with the values obtained by Shukla and Rusling for different systems using a similar method and with quenching rate constants calculated using Rehm-Weller-Marcus theory.

Determination of free formaldehyde in foundry resins as its 2,4-dinitrophenylhydrazone by liquid chromatography

Formaldehyde is a toxic component that is present in foundry resins. Its quantification is important to the characterisation of the resin (kind and degradation) as well as for the evaluation of free contaminants present in wastes generated by the foundry industry. The complexity of the matrices considered suggests the need for separative techniques. The method developed for the identification and quantification of formaldehyde in foundry resins is based on the determination of free carbonyl compounds by derivatization with 2,4-dinitrophenylhydrazine (DNPH), being adapted to the considered matrices using liquid chromatography (LC) with UV detection. Formaldehyde determinations in several foundry resins gave precise results. Mean recovery and R.S.D. were, respectively, >95 and 5%. Analyses by the hydroxylamine reference method gave comparable results. Results showed that hydroxylamine reference method is applicable just for a specific kind of resin, while the developed method has good performance for all studied resins.

The normal co-ordinate analysis, vibrational spectra and theoretical infrared intensities of some thiocarbonyl halide molecules /

TITLE: The normal co-ordinate analysis, vibrational spectra and theoretical infrared intensities of some thiocarbonyl halides. AUTHOR: J. L. Brema SUPERVISOR: Dr. D. C. Moule NUMBER OF PAGES: 89 ABSTRACT: The vibrational assignment of the five-in-plane fundamental modes of CSClBr has been made on the basis of infrared gas phase and liquid Raman spectral analyses to supplement our earlier vibrational studies. Even though the one out-of-plane fundamental was not observed spectroscopically an attempt has been made to predict its frequency. The vibrational spectra contained impurity bands and the CSClBr assignment was made only after a thorough analysis of the impurities themselves. A normal co-ordinate analysis calculation was performed assuming a Urey-Bradley force field. This calculation yielded the fundamental frequencies in good agreement with those observed after refinement of the originally transferred force constants. The theoretical frequencies are the eigenvalues of the secular equation and the calculation also gave the corresponding eigenvectors in the form of the very important LLj matrix. The [l] matrix is the transfoirmation between internal co-ordinates and normal co-ordinates and it is essential for Franck-Condon calculations on electronically excited molecules and for infrared Integrated band intensity studies. Using a self-consistent molecular orbital calculation termed "complete neglect of differential overlap" (CNDO/2) , theoretical values of equilibrium bond lengths and angleswere calcuted for a series of carbonyl and thlocarbonyl molecules. From these calculations valence force field force constants were also determined but with limited success. With the CNIX)/2 method theoretical dipole moment derivatives with respect to symmetrized internal co-ordinates were calculated and the results should be useful in a correlation with experimentally determined values.

Intramolecular carbenoid insertion : reactions of [alpha] -diazoketones derived from benzothienyl, pyrolyl and indolyl alkanoic acids with rhodium (II) acetate

Recent studies have shown that the rhodium (II) acetate decomposition chemistry observed for a-diazoketones tethered to thienyl, furanyl, and benzofuranyl moieties is dependent not only on the nature of the heteroatom but also on the length of the aliphatic tether linking the diazoketone moiety with the aromatic fragment. The present thesis expands on these results and focuses on a-diazoketones tethered to benzothiophenes, pyrroles and indoles by a methylene linker. In the case of benzothiophenes, it was shown that the rhodium catalyst decomposition of I-diazo-4-(3-benzothienyl)-2-butanone (146) and 1-diazo-4-(3benzothienyl)- 2-butanone (152) allow for the isolation of 1,2,3a,3b-tetrahydro-3Hbenzo[ b]cyclopenta[1,3]cyclopropa- [1 ,2-d]thiophen-3-one (147) and 1,2,3a,3btetrahydro- 3H-benzo[b]cyclopenta[1,3]cyclopropa[1,2-d]thiophen-3-one (153). However treatment of 1-diazo-3-(3-Benzothienyl)-2-Propanone (165) with Rh(II) acetate results in the formation of 2,3-Dihydro-1H-benzo[b]cyclopenta[d]thiophen-2-one (159), while 1diazo- 3-(2-Benzothienyl)-2-Propanone with the same condition gives 5,5-bis( 1benzothiophen- 2-ylmethyl)-2(5H)-furanone (166) along with the tricycle 159. The chemistry of the pyrrolyl and the indolyl moieties linked to terminal adiazoketone systems was also investigated. The decomposition of I-diazo-(2-pyrrolyl)-2propanone (173) results in the formation of two products; the N-H insertion product IHpyrrolizin- 2(3H)-one (176) and the alkylation product 4,6-dihydrocyclopenta[b]pyrrol5( 1 H)-one (180). When 1-Diazo-3-(3-indoly)-3-propanone (194) is treated with catalytic amount of Rh (II) 3,4-dihydrocyclopenta[b]indol-2(1H)-one (193) is isolated quantitatively. The later reaction when monitored using IH NMR the intermediate 200 can be seen whose structure was confirmed by the comparison to series of model compounds. The mechanisms underlying these reactions as well as their synthetic utility is discussed.

The vibrational spectra and the normal coordinate analysis of thiocarbonye halides /|nby C. R. Subramaniam. -- 260 St. Catharines, Ont. : [s. n.],

The infrared and the Raman spectra of eSelF has been obtained for the first time and has been analysed to give the in-plane normal vibrational frequencies of the molecule, in the ground state. A normal co-ordinate analysis has been carried out for the molecules CSF2, CSClF and eSel 2 using a Urey-Bradley type of potential function and the elements of the [L] matrix elements, the distribution of the potential energy in Urey-Bradley space, and the displacement vector diagrams for the normal modes of vibration for these molecules, have been obtained. The bond for~e constants obtained through the normal co-ordinate analysis, have given some interesting results. The stretching force constant, Kes ' varies markedly with halogen substitution and the force constants KeF and Keel also vary with substitution.

Analysis Of The A11a22 X 11a11 And A 33a22 X 1 electronic transitions in selenocarbonyl difluoride

The absorption spectrum of F2CSe in the 18800-21900 cm-1 region has been recorded at -770 C and 220 C under the conditions of medium resolution. The responsible electronic promotion is TI* + n excitation which leads to 3A2 and lA2 excited states. Progressions in vI', v2', v3" v4' and v4" have been identified in the spectrum and have been analyzed in terms of vibronic transitions between a planar ground state and a nQnplanar excited state. The - 3 - 1 - 1 - 1 origins of the a A2 + X Al and A A2 + X Al systems were assigned to the bands at 19018 cm-l and 19689 cm-l . This has given a singlet-triplet splittl. n g lA2 - 3A2 P f 671 cm -1 The out-of-plane wagging levels were found to be anharmonic. 1 -1 Barrier heights of 2483 cm- and 2923 cm were obtained for the lA2 and 3A2 upper states from a fitting of the energy levels of a Lorentzian-quadratic function to the observed levels in the out-of-plane wagging modes. 1 3 For the A2 and A2 states nonplanar equilibrium angles of 30.10 and 31.40 have been evaluated respectively. i

Synthèse stéréosélective de dérivés cyclopropaniques di-accepteurs par catalyse avec des complexes de rhodium(II)

Les dérivés cyclopropaniques di-accepteurs représentent des intermédiaires synthétiques précieux dans l’élaboration de structures moléculaires complexes, ayant des applications dans plusieurs domaines de la chimie. Au cours de cet ouvrage, nous nous sommes intéressés à la synthèse de ces unités sous forme énantioenrichie en utilisant la cyclopropanation d’alcènes par catalyse avec des complexes de Rh(II) utilisant des composés diazoïques di-accepteurs comme substrats. Suite au développement initial d’une méthode de cyclopropanation d’alcènes catalytique asymétrique utilisant des nitro diazocétones, de multiples études expérimentales quant au mécanisme de stéréoinduction dans ce type de réaction ont été effectuées. Nous avons alors pu identifier le groupement p-méthoxyphénylcétone du substrat et le catalyseur Rh2(S-TCPTTL)4 comme étant une combinaison clé pour l’atteinte de diastéréosélectivités et d’excès énantiomères élevés. Ceci a mené au développement de deux autres méthodes de cyclopropanation stéréosélectives distinctes, utilisant soit une cyano diazocétone ou un céto diazoester. Nous avons démontré l’utilité des dérivés cyclopropaniques énantioenrichis obtenus par ces trois méthodes dans une panoplie de manipulations synthétiques, dont l’addition nucléophile d’amines et de cuprates, la cycloaddition formelle avec un aldéhyde, et la synthèse de dérivés cyclopropaniques importants en chimie médicinale. Une étude structurelle approfondie des complexes de Rh(II) chiraux nous a permis de déterminer les facteurs responsables de leur pouvoir d’énantioinduction dans notre système réactionnel, ce qui a d’énormes implications dans d’autres méthodologies utilisant ces mêmes catalyseurs. Le dévoilement d’une conformation inattendue dite ‘All-up’, ainsi que de la présence d’interactions stabilisantes régissant la rigidité de cet arrangement se sont avérés cruciaux dans notre compréhension du mécanisme. Dans le cadre de cette investigation, nous avons développé une méthode générale pour la synthèse de complexes de Rh(II) hétéroleptiques, multipliant ainsi le nombre de catalyseurs accessibles dans l’élaboration éventuelle de nouvelles réactions stéréosélectives, et nous permettant d’effectuer une étude structurelle plus détaillée. De plus, nous avons développé une méthode particulièrement efficace pour la synthèse d’un autre type de dérivé cyclopropanique di-accepteur par catalyse avec des complexes de Rh(II), les cyano-cyclopropylphosphonates. Les produits de cette transformation sont obtenus avec des énantiosélectivités élevées, et sont des substrats intéressants pour des réactions tandem d’ouverture de cycle par addition nucléophile / oléfination de composés carbonylés. De plus, ces composés sont des précurseurs de molécules utiles en chimie médicinale tels que les acides aminocyclopropylphosphoniques.

Studies on the Synthesis and Transformations of a Few 2(3H)- and 3(2H)-Furanones

The thesis entitled studies on the synthesis and transformations of a few 2(3H)- and 3(2H)- furanones. Furanones represent an interesting class of heterocyclic compounds, which constitute the central ring system of many natural products. The derivatives of furan is divided, depending on their structure 2(3H)-furanones(I), 2(5H)-furanones(II), and 3(2H)-furanones(III). Systems I&II are unsatured gama lactones known as ‘butenolides’. Compounds of this type also known as ‘crotonolactones’ based on the parent crotonic acid. In conclusion a number of 2(3H)-and 3(2H)- furanones were synthesized from dibenzoylalkene precursors and were characterized on the basis of spectral analytical and X-ray data. On direct irradiation 3,3-bis(4-chloropheneyl)-5-aryl-3H-furan -2-ones underwent decarbonylation to yield the corresponding alpha, beta- unsaturated carbonyl compounds and upon sensitized irradiation they underwent dimersation arising through a 2+2 cycloaddition reaction. Our studies on 3(2H)-furanones revealed that these compounds are thermally stable, while they undergo extensive decomposition to intractable mixtures under the influence of light. Similarly, the novel dibenzoylalkenes- type systems containing hetroatomatic rings synthesized by us also underwent extensive decomposition under the influence of heat. Some of the 3(2H)-furanones synthesized by us exhibit remarkable anti-proliferative activity.