The thesis titled “Novel Strategies for the Synthesis of Organo-Sulfur Compounds Under Metal-free Reaction conditions” is presented into three main sections. Section A– deals with the synthesis of thiourea and thioamide. Section B– describes the sulfenylation of electron-rich arenes, ketones and β- diketones Section C– deals with the sulfur/fluorine assisted deacylation of α-sulfenylated β- diketones. Section A: This section is divided in to two chapters, Chapter 1 and Chapter 2. Chapter 1 of this section describes the non-isothiocyanate route to obtain trisubstituted thioureas of arylamines by using in situ generated dithiocarbamates of secondary amines. Trisubstituted thioureas of aryl amines are important precursors for the synthesis of heterocyles like 2-aminobenzothiazoles derivatives,1 amidines,2 and guanidines.3 Therefore, this strategy provides an excellent opportunity to access thioureas containing primary aryl amines without employing isothiocyanates. From the current method, the broad substrate scope was achieved with excellent yield of the corresponding products. Further, under the optimized reaction conditions a variety of functional groups like ketones, carboxylic acids, amides and sulfonamides were found to be well tolerated. A few representative examples are shown in Scheme 1.4 (a) Jordan, A. D.; Luo, C.; and Reitz, A. B. J. Org. Chem. 2003, 68, 8693. (b) Joyce, L. L.; Batey, R. A. Org. Lett. 2009, 11, 2792 and references therein. (c) Jamir, L.; Khatun, N.; Patel, B. K. RSC Adv., 2011, 1, 447. 1 Biswas, K.; Greaney, M. F. Org. Lett. 2011, 13, 4946. 2 (a) Wilson, L. J.; Klopfenstein, S. R.; Li, M. Tetrahedron Lett. 1999, 40, 3999. (b) Schneider, S. E.; Bishop, P. A.; Salazar, M. A.; Bishop, O. A.; Anslyn, E. V. Tetrahedron 1998, 54, 15063. 3 Varun, B. V.; Prabhu, K. R. RSC Adv.2013, 3, 3079. Synopsis Chapter 2 describes the rapid, high yielding and easily isolable method for the synthesis of thioamide by nucleophilic addition of electron-rich arenes to isothiocyanates. Thioamides are essential structural motifs which are found in a variety of biologically active molecules.5 They are also crucial building blocks for synthesizing sulfur conntaining heterocycles.6 The current method employs triflic acid (TfOH) to activate the nitrogen of isothiocyanate, where as, in the earlier methods AlCl3 was used.7 Also, the reaction was found to be highly regioselective and the broad substrate scope of the reaction was demonstrated (Scheme 2).85 (a) Cremlyn, R. J. An Introduction to Organosulfur Chemistry,John Wiley and Sons, Chichester, 1996. (b) Gottesman, M. M.; Fojo, T.; Bates, S. E. Nat. Rev. Cancer 2002, 2, 48; (c) Angehrn, P.; Goetschi, E.; Gmuender, H.; Hebeisen, P.; Hennig, M.; Kuhn, B.; Luebbers, T.; Reindl, P.; Ricklin, F.; Schmitt-Hoffmann, A. J. Med. Chem.2011, 54, 2207 6 (a)Shibuya, I.; Honda, K.; Gama, Y.; Shimizu, M. Heterocycles 2000, 53, 929. (b) Takido, T.; Itabashi, K.; Synthesis 1985, 430. (c) Shibuya, I.; Gama, Y.; Shimizu, M. Heterocycles 2001, 55, 381. (d) Wang, H.; Wang, L.; Shang, J.; Li, X.; Wang, H.; Gui, J.; Lei, A. Chem. Commun., 2012, 48, 76. (e) Alla, S. K.; Sadhu, P.; Punniyamurthy, T. J. Org. Chem., 2014, 79, 7502. (f) Chaudhari, P. S.; Pathare, S. P.; Akamanchi, K. G. J. Org. Chem., 2012, 77, 3716. (g) Mendoza-Espinosa, D.; Ung, G.; Donnadieu, B.; Bertrand, G. Chem. Commun.,2011, 47, 10614. (h) Potts, K. T.; Houghton, E.; Singh, U. P. J. Org. Chem., 1974, 39, 3627. 7 a) Jagodzinski, T.; Jagodzinska, E.; Jabłonski, Z. Tetrahedron 1986, (b) Jagodzinski, T. Synthesis 1988, 717. 8 Varun, B. V.; Sood, A.; Prabhu, K. R. RSC Adv.2014, 4, 60798. Scheme 2: Synthesis of thioamide Section B This section is divided in to two chapters, Chapter 1 and Chapter 2. Chapter 1 of this section describes a facile transition metal-free oxidative CDC (Cross Dehydrogenative Coupling) reaction leading to a regioselective thiolation of electron-rich arenes and hetero-arenes. This strategy provides a rare opportunity of using thione in a CDC reaction to form C–S bonds to obtain arylthiobenzoxazoles, hetero-arylthiobenzoxazoles and arylthiobenzthiazoles, which are pharmaceutically valuable compounds.9 This highly regioselective CDC reaction is unique as it requires the reversing the reactivity of sulfur to form the C–S bonds. Despite the propensity of thiols to undergo oxidation, this method provides an elegant and new avenue for synthesizing thioethers of benzazoles (Scheme 3).10 a) Greco, M. N.; Hageman, W. E.; Powell, E. T.; Tighe, J. J.; Persico, F. J. J. Med. Chem. 1992, 35, 3180. b) Zhang, J.-T.; Qi, J.; Feng, H.; Dong, Z. WO2010048603, 2010. c) Greco, M. N.; Hageman, W. E.; Powell, E. T.; Tighe, J. J.; Persico, F. J. J. Med. Chem. 1992, 35, 3180. d) Barchuk, W. T.; Dunford, P. J.; Edwards, J. P.; Fourie, A. M.; Karlsson, L.; Quan, J. M. US 2008194630. e) Koci, J.; Klimesova, V.; Waisser, K.; Kaustova, J.; Dahse, H.-M.; Moellmann, U.;Bioorg. Med. Chem. Lett. 2002, 12, 3275. 10 Varun, B. V.; Prabhu, K. R. J. Org. Chem.2014, 79, 9655. xii Synopsis Scheme 3: C-H-Functionalization of electron-rich arenes Chapter 2 is discussed in two parts, Part A and Part B. Part A: deals with the C–H functionalization of β-diketones via CDC reactions. A variety β-diketones were sulfenylated at α-position with a variety of benzazole-2-thione derivatives. Sulfenylation of β-diketones is challenging as β-diketones undergo deacylation after sulfenylation in the reaction medium.11 The highlight of this work is that the resultant products do not undergo deacylation. Under the optimal reaction conditions a variety of functional group like ketones, acids and esters were well tolerated. Also, the resultant sulfenylated β-diketones were further manipulated to α,α-disubstituted β-diketones and pyrazoles (Scheme 4).12 11 (a) Ogura, K.; Sanada, K.; Takahashi, K.; Iida, H. Tetrahedron Lett.1982, 23, 4035. (b) Zou, L.-H.; Priebbenow, D. L.; Wang, L.; Mottweiler, J.; Bolm, C. Adv. Synth. & Catal. 2013, 355, 2558. 12 Varun, B. V.; Gadde, K.; Prabhu, K. R. Org. Lett. 2015, 17, 2944. Scheme 4: C-H Functionalization of β-diketones via CDC reaction Chapter 2, Part B: deals with the C–H functionalization of ketones via CDC, which is the continuation of the above discussed work (Chapter 2, Part B). The products obtained from this method can be further modified and can be used for the synthesis of α,β-unsaturated carbonyl compounds under Trost or Julia olefination reaction conditions.13 A variety of actophenone derivatives, propiophenone derivatives and simple alkyl ketones were sulfenylated at the α-position with various benzazole-2-thiones (Scheme 5).14 Scheme 5: C-H Functionalization of ketones via CDC reaction (a) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J. Am. Chem. Soc. 1975, 98, 4887. (b) Baudin, J. B.; Hareau, G.; Julia, S. A. Tetrahedron Lett. 1991, 32, 1175. (c) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26. 14 Manuscript under preparation. Section C This section describes the ‘sulfur/fluorine assisted deacylation of β-diketones.’ Achieving a controlled mono fluorination at α- position of a ketone group is a difficult task. Therefore, an alternate approach is to have a sulfide group at α-position to a ketone (electron withdrawing moiety) and thereby providing additional stability to the generated reactive intermediate at α-position. Till date, this transformation has been achieved only by electrochemical methods.15 In continuation of our earlier work of α-sulfenyl β-diketones for exploring the synthetic utility of α-sulfenyl β-diketones (like benzylation and allylation), we performed the fluorination reaction. In this reaction, the fluorinated product (a diketone) underwent a de-acylation process to furnish the corresponding α-fluorinated ketone and we further optimized the reaction conditions and explored the substrate scope for this reaction. Under the optimized reaction conditions a variety of fluorinated products were isolated in excellent yield (Scheme 6) Scheme 6: Sulfur/Fluorine assisted deacylation of β-diketones 15Fuchigami, T.; Shimojo, M.; Konno, A.; Nakagawa, K. J. Org. Chem. 1990, 55, 6074 16 Manuscript under preparation.

Made available in DSpace on 2015-05-14T13:21:09Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3983986 bytes, checksum: 7333ac7eafa0997c880fac1331321936 (MD5) Previous issue date: 2011-06-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This work reports the synthesis, characterization, and investigation of the photoluminescent properties of β-diketonate complexes (TTA= 2-thenoyltrifluoroacetonate and DBM = dibenzoylmethanate) of trivalent lanthanides (Ln3+ = Eu3+, Tb3+ and Gd3+ ) with different phosphine oxides ligands (TPPO = triphenylphosphine oxide and HMPA= hexamethylphosphoramide). The elemental C, H, and N analyses, and complexometric titration suggested the general formulas [Ln(TTA)2(NO3)L2], [Ln(DBM)2(NO3)L2], [Ln(DBM)(NO3)2(HMPA)2], [Ln(TTA)3L2] e [Ln(DBM)3L], where L is phosphine oxide ligand. The absorption spectra in the infrared region showed that the coordination of β-diketonate and phosphine oxide ligands to Ln3+ ions occurs through the oxygen atoms of the carbonyl and P = O groups, respectively. Molar condutivity measurements show that the compounds behave as non-electrolytes in solution for the solvents methanol and acetone. The complex Tb(TTA)2(NO3)(TPPO)2 was obtained as single crystals and its structure was resolved by X-ray diffraction. The split transitions 5D0→7FJ, in general, are consistent with a chemical environment of low symmetry around the Ln3+ ion. The phosphorescence spectra of the Gd3+complexes showed the triplet state (T) bands of the ligands TTA and DBM, which were increased in energy (of the triplet state) in the bis- and mono-diketonate complexes in comparison with the tris-diketonates analogous. The tris-diketonate complexes of TTA and DBM showed a higher value of intensity parameters Ω2 when compared with their respective mono-and bis-diketonate, reflecting a chemical environment more polarizable around the ion Ln3+ to these complexes. / Este trabalho relata a síntese, caracterização e a investigação das propriedades fotoluminescentes de complexos β-dicetonatos (TTA=2-tenoiltrifluoroacetonato e DBM= dibenzoilmetanato) de íons lantanídeos trivalentes (Ln3+= Gd3+, Eu3+ e Tb3+) com diferentes ligantes fosfinóxidos (TPPO= trifenilfosfinóxido e HMPA= hexametilfosforamida). Os dados de microanálises de CHN e titulação complexométrica foram concordantes com as fórmulas gerais [Ln(TTA)2(NO3)L2], [Ln(DBM)2(NO3)L2], [Ln(DBM)(NO3)2(HMPA)2], [Ln(TTA)3L2] e [Ln(DBM)3L], onde L é um ligante fosfinóxido. Os espectros de absorção na região do infravermelho evidenciaram que a coordenação dos ligantes β-dicetonatos e fosfinóxidos aos íons Ln3+ ocorre por meio dos átomos de oxigênio dos grupos carbonila e P=O, respectivamente. As medidas de condutividades molares mostraram que os compostos comportam-se como não-eletrólitos em solução para os solventes metanol e acetona. O complexo Tb(TTA)2(NO3)(TPPO)2 foi obtido na forma de monocristais e sua estrutura foi resolvida pelo método de difração de raios-X. Os desdobramentos das transições 5D0→7FJ nos espectros dos complexos de Eu3+, de um modo geral, estão concordantes com um ambiente químico de baixa simetria em torno do íon Eu3+. Os espectros de fosforescência dos complexos de Gd3+ apresentam as bandas do estado tripleto (T) dos ligantes TTA e DBM, onde foi observado um aumento de energia do estado tripleto nos complexos bis e mono-dicetonatos em comparação com os análogos tris-dicetonatos. Os complexos tris-dicetonatos de TTA e DBM apresentaram um maior valor do parâmetro de intensidade experimental (Ω2) quando comparados com os seus respectivos bis- e mono-dicetonatos, refletindo um ambiente químico mais polarizável em torno do íon Eu3+ para estes complexos.

Made available in DSpace on 2015-05-14T13:21:12Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1743136 bytes, checksum: 691548bbf7c48feb134408fcb743336e (MD5) Previous issue date: 2011-12-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The lanthanide complexes have been extensively applied in several fields of knowledge. Most of these applications depend on the catalytic and spectroscopic properties of trivalent lanthanide ions. In this context, this work involves the synthesis of two classes of two-functionalized ligands between bases of nitrogen and β-diketones (classes A and B) order at future applications as catalysts for organic reactions and / or chemical sensors. The Class A, β-diketone linked to bidentate nitrogen ligands such as 2,2 -bipyridine and 1,10-phenanthroline were designed for this work, however no success was obtained in the last step of the synthesis. Three mixed β-diketones and pyridine ligands: 1,3-phenyl-(4-pyridyl)-propane-1,3 dione (12) (Class A), 1,3-methyl-2-(4-pyridyl)-propane-1 ,3-dione (16) and 1,3-diphenyl-2-(4-pyridyl)-propane-1 ,3-dione (17) (class B) were obtained with moderate yields. All synthesized intermediates and synthesized ligands were characterized by mass spectrometry, 1H and 13C NMR. The complex tris-β-diketonates of Eu3+ and Gd3+ were synthesized with the ligand 12. The ability of the ligand to donate energy to the lanthanide ions was evaluated by the luminescence spectra of the complex between 12 and Gd3+ ion, where it was observed that the ligand acts as "antenna" very efficient, sensitizing the luminescence of the metal center. From the complex of ligand 12 with the spectroscopic properties of Eu3+ complex formed were investigated based on data obtained from emission, excitation spectras and decay curves luminescence. From the emission spectra was possible to obtain a series of spectroscopic parameters for the complex of the Eu3+ ion where it was noticed the absence of the bands related to the fluorescence and / or phosphorescence of the ligand, suggesting that the processes of energy transfer from ligand to the excited levels of the metal center are very efficient. / Os complexos de íons lantanídeos vêm sendo intensivamente aplicados em diversas áreas do conhecimento. A maioria dessas aplicações depende das propriedades catalíticas e espectroscópicas dos íons lantanídeos trivalentes. Neste contexto, o presente trabalho envolve a síntese de duas classes de ligantes bifuncionalizados com bases nitrogenadas e β-dicetonas (classes A e B), visando futuras aplicações como catalisadores para reações orgânicas e/ ou sensores químicos. Da classe A, compostos mistos de β-dicetonas e ligantes bidentados nitrogenados, como 2,2 -bipiridina e 1,10-fenantrolina foram projetados, entretanto não obteve-se sucesso na última etapa da síntese. Três ligantes mistos de β-dicetonas e piridina,1-fenil-3-(4-piridil)-propano-1,3 diona (12) (classe A), 1,3-metil-2-(4-piridil)-propano-1,3-diona (16) e 1,3-difenil-2-(4-piridil)-propano-1,3-diona (17) (classe B), foram obtidos com rendimentos moderados. Todos os intermediários de síntese e ligantes sintetizados foram caracterizados por espectrometria de massa, RMN de 1H e 13C. Os complexos tris-β-dicetonatos de Eu3+ e Gd3+ foram sintetizados com o ligante 12. A capacidade do ligante 12 em doar energia para os íons lantanídeos foi avaliada através dos espectros de luminescência do complexo com íon Gd3+, onde observou-se que o ligante 12 atua como uma antena muito eficiente, sensibilizando a luminescência do centro metálico. A partir do complexo do ligante 12 com Eu3+ as propriedades espectroscópicas do complexo formado foram investigadas com base nos dados obtidos a partir dos espectros de emissão, excitação e curvas de decaimento de luminescência. A partir dos espectros de emissão foi possível obter uma série de parâmetros espectroscópicos para o complexo do íon Eu3+, onde percebeu-se a ausência das bandas referentes à fluorescência e/ou fosforescência do ligante, sugerindo que os processos de transferência de energia do ligante para os níveis excitados do centro metálico são muito eficientes.