Microwave-assisted iodine-catalyzed rapid synthesis of 6H-indolo[2,3-b]quinolinesOctober 12, 2017
Indoloquinoline alkaloids have received significant popularity because of their antimalarial and DNA intercalating properties as well as their use as folk medicines for the control of fever, amoebiasis and malaria. Related metabolites include cryptotackieine and norcryptotackieine which are linear indolo[2,3-b]quinoline alkaloids. These molecules have demonstrated numerous medicinal activities including antimicrobial, and cytotoxicity. They act through DNA intercalation and inhibition of topoisomerase II inhibition. Consequently, organic and medicinal chemists and biologists have become interested in their concise preparation and studies of their biological activities. A few synthetic routes have been developed for the preparation of these structurally unique and complex indole heterocycles. Interestingly, most of these available methods are one-pot methods. For example, high temperature reaction of molecular iodine-catalyzed reaction in diphenyl ether, pivalic acid and ruthenium-exchanged FAU-Y zeolite in 1,4-dioxane is performed. N-Bromosuccinimide at room temperature is found to be good for this purpose. The principal limitation is that almost all of these methods require a very long time. Moreover, the yields of the target molecules are low.
The current research is aimed to develop an efficient synthetic method for the synthesis of indoloquinoline alkaloids mentioned above. Considering the known procedures and analyzing the conditions of the experiments, the iodine-catalyzed tandem method is proved to be excellent. Despite the superiority of iodine, this method produces products with low to moderate yields, requires long reaction time and high temperature. Therefore, an improvement of molecular iodine-catalyzed reaction for this purpose is necessary.
Our research group has been exploring microwave-induced reactions for more than 25 years. Reactions conducted under microwave oven are known to be rapid and successful at much less drastic conditions. Moreover, they also produce the target molecules in better yields without giving side reactions in most of the examples. In conventional methods, unwanted side reactions in many instances lower the yields of the products or produce mixture of products and therefore, isolation of the desired compounds become tedious. On the basis of several successes on microwave-induced chemistry and our interests in the preparation of medicinally useful compounds, we have investigated the preparation of cryptotackieine and norcryptotackieine and their derivatives in automated microwave oven in tightly sealed reaction container.
Indole-3-carboxyaldehyde and two equivalents of aniline in presence of 10 mol% of molecular iodine at 600C and 300 watt power in a sealed vessel are irradiated in an automated microwave. It is interesting to note that the reaction proceeds rapidly with an increase in the yield of the product compared to the conventional heating (oil bath or heating mantle) at much higher temperature. The structure of the starting reactants and products suggests a most probable mechanism. Dehydration to imine from aldehyde and amine, nucleophilic reaction of the imine, annulation and subsequent aromatization occurs in a tandem process in a one-pot method.
This method is extended for the preparation of 6H-indolo[2,3-b]quinolines. As expected, the previously known compounds are synthesized very rapidly and with simple work-up, and without extensive purification. No solvent is used when one of the reactants is liquid or oil. These reactions are also performed in the presence of solvents (THF, MeOH, CHCl3, and CH2Cl2). THF and MeOH are proved to be the best solvent whereas CHCl3 and CH2Cl2 are moderately good for this method.
An expeditious simple and rapid microwave-assisted procedure for the synthesis of significant types of indoloquinolines using molecular iodine as catalyst in a one-pot is developed. The procedure described herein is the first rapid method for the synthesis of novel indoloquinolines. The rate acceleration by microwave-induced method is probably due to the alteration of the transition state of the series of reactions that occur in this tandem process. The benefit of this process is the lowered energy consumption compared to traditional method under reflux or high temperature that requires input of latent heat of vaporization. In this method, vaporization is not possible and so little expenditure of latent heat occurs. The non-ionizing radiation of the microwave is absorbed very efficiently by the reactants and polar solvents and thereby accelerates the process in an unbelievable way.
aDepartment of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India;
bCurrent Address: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, United States
cCSIR-National Institute of Oceanography, Regional Centre, Kochi 682 018, India
dDepartment of Chemistry, The University of Texas-Pan American, Edinburg, TX 78539, United States; eCurrent Address: Community Health System of South Texas, 3135 South Sugar Road, Edinburg, TX 78539, United States; Phone: 281-813-2104, Fax: 956-259-8085; Email: email@example.com; firstname.lastname@example.org
Bentham Science Publishers
Related Molecules Articles:
Researchers from Canada, the UK and Germany have developed a new experimental technique to take 3-D images of molecules in action.
Stuart Lindsay, a researcher at Arizona State University's Biodesign Institute, has devised a clever means of identifying carbohydrate molecules quickly and accurately.
Molecules from the solvent environment that at first glance seem to be uninvolved can be essential for chemical reactions.
Berkeley Lab and UC Berkeley Researchers have developed nanoscale display cases that enables new atomic-scale views of hard-to-study chemical and biological samples.
Hot molecules are found in extreme environments such as the edges of fusion reactors.
University of Iowa chemists have learned about a molecular assembly that may help create quicker, more responsive touch screens, among other applications.
An international research team describes the methods of winding up molecules into screw-shaped structures.
A new method allows scientists at ETH Zurich and IBM to fabricate artificial molecules out of different types of microspheres.
A new study may have uncovered the fountain of youth: plant extracts containing the six best groups of anti-aging molecules ever seen.
A great childhood pleasure is playing with Legos® and marveling at the variety of structures you can create from a small number of basic elements.
Related Molecules Reading:
Molecules: The Elements and the Architecture of Everything
by Theodore Gray (Author), Nick Mann (Photographer)
In his highly anticipated sequel to The Elements, Theodore Gray demonstrates how the elements of the periodic table combine to form the molecules that make up our world.
Everything physical is made up of the elements and the infinite variety of molecules they form when they combine with each other. In Molecules, Theodore Gray takes the next step in the grand story that began with the periodic table in his best-selling book, The Elements: A Visual Exploration of Every Known Atom in the Universe. Here, he explores through fascinating stories and... View Details
Reactions: An Illustrated Exploration of Elements, Molecules, and Change in the Universe
by Theodore Gray (Author)
The long-awaited third installment in Theodore Gray's iconic "Elements" trilogy. The first two titles, Elements and Molecules, have sold more than 1.5 million copies worldwide.
With Reactions bestselling author Theodore Gray continues the journey through our molecular and chemical world that began with the tour de force The Elements and continued with Molecules. In The Elements, Gray gave us a never-before-seen, mesmerizing photographic view of the 118 elements in the periodic table. In Molecules, with the same phenomenal... View Details
Elements: A Visual Exploration of Every Known Atom in the Universe
by Theodore Gray (Author), Nick Mann (Photographer)
The Elements has become an international sensation, with over one million copies in-print worldwide.
The highly-anticipated paperback edition of The Elements is finally available.
An eye-opening, original collection of gorgeous, never-before-seen photographic representations of the 118 elements in the periodic table.
The elements are what we, and everything around us, are made of. But how many elements has anyone actually seen in pure, uncombined form? The Elements provides this rare opportunity. Based on seven years of... View Details
Molecules Of Emotion: The Science Behind Mind-Body Medicine
by Candace B. Pert (Author)
Why do we feel the way we feel? How do our thoughts and emotions affect our health? Are our bodies and minds distinct from each other or do they function together as parts of an interconnected system?
In her groundbreaking book Molecules of Emotion, Candace Pert provides startling and decisive answers to these and other challenging questions that scientists and philosophers have pondered for centuries.
Her pioneering research on how the chemicals inside our bodies form a dynamic information network, linking mind and body, is not only provocative, it is revolutionary. By... View Details
DMT: The Spirit Molecule: A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences
by Rick Strassman (Author)
A clinical psychiatrist explores the effects of DMT, one of the most powerful psychedelics known.
• A behind-the-scenes look at the cutting edge of psychedelic research.
• Provides a unique scientific explanation for the phenomenon of alien abduction experiences.
From 1990 to 1995 Dr. Rick Strassman conducted U.S. Government-approved and funded clinical research at the University of New Mexico in which he injected sixty volunteers with DMT, one of the most powerful psychedelics known. His detailed account of those sessions is an extraordinarily riveting inquiry... View Details
Napoleon's Buttons: How 17 Molecules Changed History
by Penny Le Couteur (Author), Jay Burreson (Author)
Napoleon's Buttons is the fascinating account of seventeen groups of molecules that have greatly influenced the course of history. These molecules provided the impetus for early exploration, and made possible the voyages of discovery that ensued. The molecules resulted in grand feats of engineering and spurred advances in medicine and law; they determined what we now eat, drink, and wear. A change as small as the position of an atom can lead to enormous alterations in the properties of a substance-which, in turn, can result in great historical shifts.
With lively prose and an... View Details
Explore Atoms and Molecules!: With 25 Great Projects (Explore Your World)
by Janet Slingerland (Author), Matt Aucoin (Illustrator)
Atoms and molecules are the basic building blocks of matter. Matter is every physical thing around us in the universe, including our own bodies! In Explore Atoms and Molecules! With 25 Great Projects, readers ages 7 to 10 investigate the structure of atoms and learn how atoms fit together to form molecules and materials.
If everything is made out of atoms and molecules, why do people look different from dogs and doorknobs? In Explore Atoms and Molecules, readers discover that the characteristics of a material are determined by the way the atoms and molecules connect, and... View Details
The Billion Dollar Molecule: One Company's Quest for the Perfect Drug
by Barry Werth (Author)
Join journalist Barry Werth as he pulls back the curtain on Vertex, a start-up pharmaceutical company, and witness firsthand the intense drama being played out in the pioneering and hugely profitable field of drug research. Founded by Joshua Boger, a dynamic Harvard- and Merck-trained scientific whiz kid, Vertex is dedicated to designing -- atom by atom -- both a new life-saving immunosuppressant drug, and a drug to combat the virus that causes AIDS.
You will be hooked from start to finish, as you go from the labs, where obsessive, fiercely competitive scientists struggle for a... View Details
Taste Buds and Molecules: The Art and Science of Food, Wine, and Flavor
by Francois Chartier (Author)
"If Catalan superchef Ferran Adria is the leading missionary of molecular gastronomy, Mr. Chartier is his counterpart with a corkscrew."—Globe and Mail
This award-winning book, now available for the first time in English in the U.S., presents a cutting-edge approach to food and wine pairing. Sommelier Francois Chartier has spent the better part of two decades collaborating with top scientists and chefs to map out the aromatic molecules that give foods and wines their flavor. Armed with the results of his extensive research, Chartier has been able to identify why certain... View Details
We Are All Made of Molecules
by Susin Nielsen (Author)
*"This savvy, insightful take on the modern family makes for nearly nonstop laughs."—Kirkus Reviews, Starred
Stewart, 13: Socially clueless genius.
Ashley, 14: Popular with everyone but her teachers
Ashley's and Stewart's worlds collide when Stewart and his dad move in with Ashley and her mom. The Brady Bunch it isn't. Stewart is trying to be 89.9 percent happy about it--he's always wanted a sister. But Ashley is 110 percent horrified. She already has to hide the real reason her dad moved out; “Spewart” could further threaten her... View Details