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Niementowski Quinoline Synthesis Essay

Laboratorio de Radicales Libres y Química Computacional (IQOG, CSIC), Madrid, Spain, Departamento de Química Inorgánica y Química Técnica, Facultad de Ciencias, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain, and iMed.UL, Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Forcas Armadas, 1600-083 Lisbon, Portugal

Biography

José Marco-Contelles is Research Professor (“Profesor de Investigación del CSIC”). His main scientific interests include heterocyclic chemistry (synthesis and biological evaluation of molecules for neurodegenerative diseases), free radical chemistry, and transition metal promoted cycloisomerization of polyunsaturated precursors.

Biography

Elena Pérez-Mayoral studied chemistry at the University Complutense of Madrid (Spain), where she obtained her Ph.D. (Organic Photochemistry) in 1999. In 1999, she joined Prof. Ballesteros’ group at the UNED, as postdoctoral fellow, working on the design, synthesis and characterization of new contrast agents for 1H NMR Spectroscopic Imaging. In 2007, she joined the Department of Inorganic and Technique Chemistry at the Faculty of Science (UNED), where she holds a position as Research Assistant. Her present research interests are mainly focused onto the study of different organic transformations catalyzed by inorganic supports such as modified zeolites and clays, all of them in the green chemistry context.

Biography

Abdelouahid Samadi was born in Morocco in 1972. He received his Ph.D. in Chemistry in 2001 at the Universidad Politécnica de Valencia (Spain) under the guidance of Prof. Miguel A. Miranda working on “Lipidic peroxidation photosensitized by drugs containing a benzophenone-like chromophore”. Then he moved to the Consiglio Nazionale Delle Ricerche (CNR), Istituto per la Sintesi Organica e Fotoreativitá (ISOF) (Bologna − Italy) under the supervision of Prof. C. Chrysostomos, where he worked in the field of cis−trans isomerization of unsaturated fatty acid induced by thiyl radicals. In 2004, he joined the Instituto de Quimica Orgánica General (CSIC). He is currently working in the group of Prof. José Marco-Contelles caring out the synthesis of multipotent drugs for Alzheimer’s disease.

Biography

Maria do Carmo Carreiras received her degree in Pharmacy from University of Lisbon in 1977, her Master Sci. in Chemistry from University Nova of Lisbon in 1987, and her Ph.D. in Pharmaceutical Chemistry from University of Lisbon in 1989. In 1985, she was a fellow at the Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France, working under the direction of Prof. H.-P. Husson. From 1986 to 1988, she was a Ph.D. student at Instituto de Química Orgánica General (IQOG) of Madrid. In 2006, she was appointed Associate Professor at Faculty of Pharmacy, University of Lisbon. Her present research interests include the rational design of dual cholinesterase/monoamine oxidase inhibitors targeted for Alzheimerʼs disease.

Biography

Elena Soriano obtained her Ph.D. degree in 2003 at UNED (Madrid, Spain) under the supervision of Prof. Paloma Ballesteros. Later, she joined Dr. Sebastián Cerdánʼs group, working at the Instituto de Investigaciones Biomédicas as a postdoctoral fellow from Gobierno de La Rioja (2005−2006) and from MEC (Juan de la Cierva contract, 2006−2008). Since 2008, she has held a position as Científico Titular CSIC at the Instituto de Química Orgánica General de Madrid (CSIC). Her research interests focus on the application of computational tools to the study of reaction mechanisms and drug design.

The Niementowski quinoline synthesis is the chemical reaction of anthranilic acids and ketones (or aldehydes) to form γ-hydroxyquinoline derivatives.[1][2][3][4]

Overview[edit]

In 1894, Niementowski reported that 2-phenyl-4-hydroxyquinoline was formed when anthranilic acid and acetophenone were heated to 120–130 °C. He later found that at higher heat, 200 °C, anthranilic acid and heptaldehyde formed minimal yields of 4-hydroxy-3-pentaquinoline.[5] Several reviews have been published.[6][7]

Variations[edit]

The temperatures required for this reaction make it less popular than other quinoline synthetic procedures. However, variations have been proposed to make this a more pragmatic and useful reaction. Adding phorphorous oxychloride to the reaction mixture to mediate a condensation to make both isomers of an important precursor to an important α1-adrenoreceptor antagonist.[8] When the 3 position of an arylketone is substituted, it has been shown that a Niementowski-type reaction with propionic acid can produce a 4-hydroxyquinoline with 2-thiomethyl substitute.[9] The method has also been altered to occur with a catalytic amount of base,[10] or in the presence of polyphosphoric acid.[11]

Mechanism[edit]

Because of the similarity of these to the reagents in the Friedlander quinolone synthesis, a benzaldehyde with an aldehyde or ketone, the Niementowski quinoline synthesis mechanism is minimally different from that of the Friedländer synthesis. While studied in depth, two reaction pathways are possible and both have significant support.[5] The reaction is thought to begin with the formation of a Schiff base, and then proceed via an intra-molecular condensation to make an imine intermediate. There is then a loss of water that leads to a ring closing and formation of the quinoline derivative. Most evidence supports this as the mechanism in normal conditions of 120–130 °C. Alternatively, the reaction begins with an intermolecular condensation and subsequent formation of the imine intermediate.[12] The latter has been shown to be more common under acidic or basic conditions. A similar pathway has been proposed for the Niementowski quinazoline synthesis.[13]

References[edit]

  1. ^Niementowski, S. v. (1894). "Synthesen der Chinolinderivate". Chemische Berichte. 27 (2): 1394–1403. doi:10.1002/cber.18940270242. 
  2. ^Niementowski, S. v.; Orzechowski, B. (1895). "Synthesen der Chinolinderivate aus Anthranilsäure und Aldehyden". Chemische Berichte. 28 (3): 2809–2822. doi:10.1002/cber.18950280393. 
  3. ^Niementowski, S. v. (1905). "Ueber die Einwirkung des Benzoylessigesters auf Anthranilsäure (III. Mittheilung über Synthesen der Chinolinderivate)". Chemische Berichte. 38 (2): 2044–2051. doi:10.1002/cber.190503802142. 
  4. ^Niementowski, S. v. (1907). "Über die Einwirkung des Benzoylessigesters auf Anthranilsäure auf Anthrailsäure". Chemische Berichte. 40 (4): 4285–4294. doi:10.1002/cber.19070400444. 
  5. ^ abHartz, pp. 376–384
  6. ^Manske, R. H. (1942). "The Chemistry of Quinolines". Chem. Rev.30: 127. doi:10.1021/cr60095a006. 
  7. ^Hisano, T. (1973). "Recent Studies on the Modified Niementowski 4-Quinazolone Synthesis. A Review". Org. Prep. Proced. Int.5 (4): 145–193. doi:10.1080/00304947309355565. 
  8. ^Rosini, M.; Anontello, A.; Cavalli, A.; Bolognesi, M.; Minarini, A.; Marucci, G.; Poggesi, E.; Melchiorre, C. (2003). "Prazosin-Related Compounds. Effect of Transforming the Piperazinylquinazoline Moiety into an Aminomethyltetrahydroacridine System on the Affinity for α1-Adrenoreceptors". J. Med. Chem.46 (23): 4895–4903. doi:10.1021/jm030952q. 
  9. ^Wang, M. -X., Liu, Y., Huang, Z, -T.; Liu; Huang (2001). "Novel and convenient synthesis of polyfunctionalized quinolines, quinolones and their annulation reactions". Tetrahedron Letters. 42 (13): 2553–2555. doi:10.1016/S0040-4039(01)00231-3. 
  10. ^Chong, R. J.; Siddiqui, M. A.; Sneickus, V. (1983). "The synthesis of chiral annulet 1,4,7-triazacyclononanes". Tetrahedron Letters. 43 (21): 3795–3798. doi:10.1016/S0040-4039(02)00705-0. 
  11. ^Nahnda Kumar, R., Suresh, T., Mylithi, A., Mohan, P. S.; Suresh; Mythili; Mohan (2001). "A facile entry to pyrimido[4,5-b]quinolines and its thio analogues". Heterocycl. Commun. 7 (2): 193–198. doi:10.1515/HC.2001.7.2.193. 
  12. ^Marco-Contelles, José; PéRez-Mayoral, Elena; Samadi, Abdelouahid; Carreiras, María do Carmo; Soriano, Elena (2009). "Recent Advances in the Friedländer Reaction". Chemical Reviews. 109 (6): 2652–2671. doi:10.1021/cr800482c. PMID 19361199. 
  13. ^Hartz, pp. 440–453

Bibliography[edit]

  • Hartz, R. (2011) in Name Reactions in Heterocyclic Chemistry II, Jie Jack Li, E. J. Corey (eds.), Wiley, ISBN 978-0-470-08508-0.

See also[edit]

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