Highlights
Modification of BHT has a significant multivariate effect on antioxidant efficiency.

BDE is the key to rational design and development of antioxidants.

Antioxidant performance of BHT is mainly depending on 13 very crucial parameters.

MPAO is a promising way to increase antioxidant and pharmacological activities.

---

Abstract

Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant recognized as safe for use in foods containing fats, pharmaceuticals, petroleum products, rubber and oil industries. In the past two decades, there has been growing interest in finding novel antioxidants to meet the requirements of these industries. To accelerate the antioxidant discovery process, researchers have designed and synthesized a series of BHT derivatives targeting to improve its antioxidant properties to be having a wide range of antioxidant activities markedly enhanced radical scavenging ability and other physical properties. Accordingly, some structure–activity relationships and rational design strategies for antioxidants based on BHT structure have been suggested and applied in practice. We have identified 14 very sensitive parameters, which may play a major role on the antioxidant performance of BHT. In this review, we attempt to summarize the current knowledge on this topic, which is of significance in selecting and designing novel antioxidants using a well-known antioxidant BHT as a building-block molecule. Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized.

European Journal of Medicinal Chemistry

Volume 101, 28 August 2015, Pages 295–312

Review article

Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): A review

• Wageeh A. Yehye^{a, ,} ,
• Noorsaadah Abdul Rahman^b,
• Azhar Ariffin^b,
• Sharifah Bee Abd Hamid^a,
• Abeer A. Alhadi^b,
• Farkaad A. Kadir^c,
• Marzieh Yaeghoobi^d

• ^aNanotechnology & Catalysis Research Centre, (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, 50603 Kuala Lumpur, Malaysia
• ^bDepartment of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
• ^cDivision of Human Biology, Faculty of Medicine, International Medical University, 57000 Kuala Lumpur, Malaysia
• ^dDrug Design and Development Research Group, Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
• http://www.sciencedirect.com/science/article/pii/S022352341530101X

doi:10.1016/j.ejmech.2015.06.026

• 
  

  1st Wageeh Yehye

  University of Malaya
• 
  

  2nd Noor Rahman

  University of Malaya
• 
  

  3rd Azhar Ariffin

  University of Malaya
• 
  

  4th Sharifah Bee Abd Hamid

   University of Malaya
• 
  

  5th Abeer Abdulhadi Abdulqader

  University of Malaya
• 
  

  6th Farkaad A Kadir

  International Medical University (IMU)
• 
  

  7th Marzieh Yaeghoobi

   University of Malaya

SEE
https://www.researchgate.net/publication/278050005_ChemInform_Abstract_Understanding_the_Chemistry_Behind_the_Antioxidant_Activities_of_Butylated_Hydroxytoluene_BHT_A_Review/figures












///////////Antioxidant, Butylated hydroxytoluene, Free radical, Reactive oxygen species, Phenol

Multicomponent Multicatalyst Reactions (MC)2R:  One-Pot Synthesis of 3,4-Dihydroquinolinones Lei Zhang, Lorenzo Sonaglia, Jason Stacey, and Mark Lautens Org. Lett. 2013, 15, 2128-2131. DOI:10.1021/ol4006008 . A Rh/Pd/Cu catalyst system led to an efficient synthesis of dihydroquinolinones in one-pot, two operations. The reaction features the first triple metal-catalyzed transformations in one reaction vessel, without any intermediate workup. The conjugate-addition/amidation/amidation reaction sequence is highly modular, divergent, and practical. Multicomponent Multicatalyst Reactions (MC)2R: One-Pot Synthesis of 3,4-Dihydroquinolinones Lei Zhang, Lorenzo Sonaglia, Jason Stacey, and Mark Lautens* Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada Org. Lett., 2013, 15 (9), pp 2128–2131 DOI: 10.1021/ol4006008 Publication Date (Web): April 19, 2013 Copyright © 2013 American Chemical Society mlautens@chem.utoronto.ca http://pubs.acs.org/doi/abs/10.1021/ol4006008 Mark Lautens Mark Lautens , O.C. University Professor J. Bryan Jones Distinguished Professor AstraZeneca Professor of Organic Chemistry NSERC/Merck-Frosst Industrial Research Chair Department of Chemistry Davenport Chemical Laboratories 80 St. George St. University of Toronto Toronto, Ontario M5S 3H6 Tel: (416) 978-6083 Fax: (416) 946-8185 E-Mail: mlautens@chem.utoronto.ca Curriculum Vitae Personal Place and Date of Birth Hamilton, Ontario, Canada July 9, 1959 Education Harvard University NSERC PDF with D. A. Evans 1985 - 1987 University of Wisconsin-Madison Ph.D. with B. M. Trost 1985 University of Guelph B.Sc. - Distinction 1981 Academic Positions J. Bryan Jones Distinguished Professor University of Toronto 2013 - 2018 University Professor University of Toronto 2012 - present NSERC/Merck Frosst Industrial Research Chair NSERC/Merck Frosst 2003 - 2013 AstraZeneca Professor of Organic Synthesis University of Toronto 1998 - present Professor University of Toronto 1995 - 1998 Associate Professor University of Toronto 1992 - 1995 Assistant Professor University of Toronto 1987 - 1992 Awards & Honors University of Toronto Alumni Faculty Award University of Toronto 2016 CIC Catalysis Award CSC 2016 Officer of the Order of Canada Governor General 2014 Killam Research Fellowship Canada Council for the Arts 2013-2015 CIC Medal Chemical Institute of Canada 2013 Fellow of the Royal Society of UK Royal Society of Chemistry 2011 Pedler Award Royal Society of Chemistry 2011 Senior Scientist Award Alexander von Humboldt Foundation Berlin, Aachen and Gottingen 2009-2014 Visiting Professor University of Berlin 2009 Visiting Professor Université de Marseilles 2008 ICIQ Summer School ICIQ Tarragona, Spain 2008 Attilio Corbella Summer School Professor Italian Chemical Society 2007 Arthur C. Cope Scholar Award American Chemical Society 2006 Alfred Bader Award Canadian Society for Chemistry 2006 R. U. Lemieux Award Canadian Society for Chemistry 2004 Solvias Prize Solvias AG 2002 Fellow of the Royal Society of Canada Royal Society of Canada 2001 Areas of Research Interest and Expertise new synthetic methods metal catalyzed cycloaddition and annulation reactions asymmetric catalysis with focus on rhodium, nickel and palladium catalysts cyclopropane synthesis and reactions hydrometallation reactions reactions of organosilicon and organotin compounds fragmentation reactions new routes to medicinally/biologically interesting compounds heterocycle synthesis using metal catalysts ////////////

Heterogeneous catalytic approaches in C-H activation reactions

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC00385K, Critical Review

Stefano Santoro, Sergei I. Kozhushkov, Lutz Ackermann, Luigi Vaccaro
This review summarizes the development of user-friendly, recyclable and easily separable heterogeneous catalysts for C-H activation during the last decade until December 2015.

http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC00385K?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Despite the undisputed advances and progress in metal-catalyzed C–H functionalizations, this atom-economical approach had thus far largely been developed with the aid of various metal catalysts that were operative in a homogeneous fashion. 

While thereby major progress was accomplished, these catalytic systems featured notable disadvantages, such as low catalyst recyclability. This review summarizes the development of user-friendly, recyclable and easily separable heterogeneous catalysts for C–H activation.

This strategy was characterized by a remarkably broad substrate scope, considerable levels of chemo- and site-selectivities and proved applicable to C–C as well as C–heteroatom formation processes. 

Thus, recyclable catalysts were established for arylations, hydroarylations, alkenylations, acylations, nitrogenations, oxygenations, or halogenations, among others. The rapid recent progress in selective heterogeneous C–H functionalizations during the last decade until December 2015 is reviewed.

Heterogeneous catalytic approaches in C–H activation reactions

Stefano Santoro,^a   Sergei I. Kozhushkov,^b  Lutz Ackermann*^b and   Luigi Vaccaro*^a  

*

Corresponding authors

^a

Laboratory of Green Synthetic Organic Chemistry, Dipartimento di Chimica Biologia e Biotecnologie, Università di Perugia, Via Elce di Sotto, 8 – 06123 Perugia, Italy 
E-mail: luigi.vaccaro@unipg.it
Web: http://www.dcbb.unipg.it/greensoc

^b

Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany 
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
Web: http://www.ackermann.chemie.uni-goettingen.de

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC00385K     

Laboratory of Green Synthetic Organic Chemistry, Dipartimento di Chimica Biologia e Biotecnologie, Università di Perugia, Via Elce di Sotto, 8 – 06123 Perugia, Italy 
E-mail: luigi.vaccaro@unipg.it
Web: http://www.dcbb.unipg.it/greensoc

Extra clips
 C-H Activation :: Wiley-VCH Hot Topics

www.wiley-vch.de

 
 The Yu Lab

www.scripps.edu

"Ligand-Enabled Triple C-H Activation Reactions: One-Pot Synthesis of Diverse 4-Aryl-2-quinolinones from Propionamides" Angew. Chem. Int. Ed. 2014, 53, ...

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N-Butylpyrrolidinone as a dipolar aprotic solvent for organic synthesis

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC00932H, Paper

James Sherwood, Helen L. Parker, Kristof Moonen, Thomas J. Farmer, Andrew J. Hunt
N-Butylpyrrolidinone (NBP) has been demonstrated as a suitable safer replacement solvent for N-Methylpyrrolidinone (NMP) in selected organic syntheses.

N-Butylpyrrolidinone as a dipolar aprotic solvent for organic synthesis

N-Butylpyrrolidinone as a dipolar aprotic solvent for organic synthesis

James Sherwood,^a   Helen L. Parker,^a   Kristof Moonen,^b  Thomas J. Farmer^a and   Andrew J. Hunt*^a  

*Corresponding authors

^aGreen Chemistry Centre of Excellence, Department of Chemistry, University of York, UK
E-mail: andrew.hunt@york.ac.uk

^bEastman Chemical Company, Pantserschipstraat 207 – B-9000, Gent, Belgium

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC00932H

http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC00932H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

 

Dipolar aprotic solvents such as N-methylpyrrolidinone (or 1-methyl-2-pyrrolidone (NMP)) are under increasing pressure from environmental regulation. NMP is a known reproductive toxin and has been placed on the EU “Substances of Very High Concern” list. Accordingly there is an urgent need for non-toxic alternatives to the dipolar aprotic solvents. N-Butylpyrrolidinone, although structurally similar to NMP, is not mutagenic or reprotoxic, yet retains many of the characteristics of a dipolar aprotic solvent. This work introduces N-butylpyrrolidinone as a new solvent for cross-coupling reactions and other syntheses typically requiring a conventional dipolar aprotic solvent.

////N-Butylpyrrolidinone, dipolar aprotic solvent , organic synthesis

Dehydrogenative [2 + 2 + 1] Heteroannulation Using a Methyl Group as a One-Carbon Unit: Access to Pyrazolo[3,4-c]quinolines

 

Dehydrogenative [2 + 2 + 1] Heteroannulation Using a Methyl Group as a One-Carbon Unit: Access to Pyrazolo[3,4-c]quinolines

Guo-Bo Deng^†, Hai-Bing Li^†, Xu-Heng Yang^†, Ren-Jie Song^*†, Ming Hu^†, and Jin-Heng Li^*†‡

^† State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China

^‡ State Key Laboratory of Applied Organic Chemistry Lanzhou University, Lanzhou 730000, China

Org. Lett., Article ASAP

DOI: 10.1021/acs.orglett.6b00618

Publication Date (Web): April 28, 2016

Copyright © 2016 American Chemical Society

*E-mail: srj0731@hnu.edu.cn., *E-mail: jhli@hnu.edu.cn.

http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b00618

 A practical and straightforward access to pyrazolo[3,4-c]quinolines by molecular sieve mediated dehydrogenative [2 + 2 + 1] heteroannulation of N-(o-alkenylaryl)imines with aryldiazonium salts is described using a sp³-hybrid carbon atom as a one-carbon unit. The reaction enables the formation of three new chemical bonds, a C–C bond and two C–N bonds, in a single reaction and features simple operation and excellent functional group tolerance.

/////////Dehydrogenative [2 + 2 + 1] Heteroannulation,   Pyrazolo[3,4-c]quinolines

A continuous-flow process for the preparation of m-nitrothioanisole has been set up. The starting material m-nitroaniline was diazotized to give diazonium chloride, followed by azo-coupling with sodium thiomethoxide to give 1-(methylthio)-2-(3-nitrophenyl)diazene, then dediazoniated to gain m-nitrothioanisole in high yield. The continuous-flow process minimized accumulation of the energetic intermediate diazonium salt and has a better capacity for adapting large-scale production. A solvent was introduced in the azo-coupling section to create a biphasic flow system. Side products were inhibited eminently in this flow process.

Continuous-Flow Process for the Synthesis of m-Nitrothioanisole

Zhiqun Yu^†, Xiaoxuan Xie^†, Hei Dong^†, Jiming Liu^‡, and Weike Su^*†‡

^† National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. China

^‡ Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. China

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.6b00023

Publication Date (Web): March 24, 2016

Copyright © 2016 American Chemical Society

*Tel.: (+86)57188320899. E-mail: pharmlab@zjut.edu.cn.

http://pubs.acs.org/doi/abs/10.1021/acs.oprd.6b00023
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Eco-friendly construction of highly functionalized chromenopyridinones by an organocatalyzed solid-state melt reaction and their optical properties

Green Chem., 2016, 18,1488-1494
DOI: 10.1039/C5GC02658J, Paper

Sanjay Paul, Yong Rok Lee
Diverse chromenopyridinone derivatives were synthesized under organocatalytic solid-state melt conditions. The optical properties of these [small pi]-expanded chromenopyridine derivatives were examined.
The content of this RSS Feed (c) The Royal Society of Chemistry

Eco-friendly construction of highly functionalized chromenopyridinones by an organocatalyzed solid-state melt reaction and their optical properties

http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C5GC02658J?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Eco-friendly construction of highly functionalized chromenopyridinones by an organocatalyzed solid-state melt reaction and their optical properties

Sanjay Paul^a and   Yong Rok Lee*^a  

Hide Affiliations

*

Corresponding authors

^a

School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea
E-mail: yrlee@yu.ac.kr
Fax: +82-53-810-4631
Tel: +82-53-810-2529

Green Chem., 2016,18, 1488-1494

DOI: 10.1039/C5GC02658J

The library construction of highly functionalized and diverse chromenopyridinones was achieved by three-component reactions of various 4-hydroxycoumarins with ammonium acetate and 3-formylchromones under L-proline catalyzed solid-state melt conditions. The advantages of this protocol include the use of an inexpensive organocatalyst, avoidance of toxic organic solvents, environmentally benign conditions, an easy work-up procedure and good to excellent product yields. The optical properties of these π-expanded varieties of the synthesized chromenopyridinone derivatives were also examined. A chromeno[4,3-b]pyridine nucleus bearing an electron donating group exhibited strong emission in the blue-green region of the visible spectrum.

////////

.

High Trans Kinetic Selectivity in Ruthenium-Based Olefin Cross-Metathesis through Stereoretention

Adam M. Johns^†, Tonia S. Ahmed^‡, Bradford W. Jackson^†, Robert H. Grubbs^*‡, and Richard L. Pederson^*†

^‡ The Arnold and Mabel Beckman Laboratory of Chemical Synthesis, Division of Chemistry and Chemical Engineering. California Institute of Technology, Pasadena, California 91125, United States

^† Materia, Inc., Pasadena, California 91107, United States

Org. Lett., 2016, 18 (4), pp 772–775

DOI: 10.1021/acs.orglett.6b00031

Publication Date (Web): February 03, 2016

Copyright © 2016 American Chemical Society

*E-mail: rhg@caltech.edu., *E-mail: rpederson@materia-inc.com.

 http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b00031





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The dengue virus and related flaviviruses are an increasing global health threat. In this perspective, we comment on and review medicinal chemistry efforts aimed at the prevention or treatment of dengue infections. We include target-based approaches aimed at viral or host factors and results from phenotypic screenings in cellular assay systems for viral replication. This perspective is limited to the discussion of results that provide explicit chemistry or structure–activity relationship (SAR), or appear to be of particular interest to the medicinal chemist for other reasons. The discovery and development efforts discussed here may at least partially be extrapolated toward other emerging flaviviral infections, such as West Nile virus. Therefore, this perspective, although not aimed at flaviviruses in general, should also be able to provide an overview of the medicinal chemistry of these closely related infectious agents.

READ AT
http://pubs.acs.org/doi/full/10.1021/acs.jmedchem.5b01653

The Medicinal Chemistry of Dengue Virus

Mira A. M. Behnam^†, Christoph Nitsche^†, Veaceslav Boldescu^†§, and Christian D. Klein^*†

^† Medicinal Chemistry, Institute of Pharmacy and Molecular Biotechnology IPMB, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany

^§ Laboratory of Organic Synthesis, Institute of Chemistry of the Academy of Sciences of Moldova, Academiei 3, 2028 Chisinau, Moldova

J. Med. Chem., Article ASAP

DOI: 10.1021/acs.jmedchem.5b01653

Publication Date (Web): January 15, 2016

Copyright © 2016 American Chemical Society

*C. D. Klein, phone +49-6221-544875, e-mail c.klein@uni-heidelberg.de.

ACS Editors' Choice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Biography

Mira A. M. Behnam studied pharmacy and biotechnology at The German University in Cairo, where she obtained her B.Sc. degree (2009) and M.Sc. degree (2011) in Pharmaceutical Chemistry in collaboration with Würzburg University. Since 2013, she is DAAD scholarship holder and Ph.D. candidate in the group of Prof. Christian Klein (Heidelberg University) working on the development of potent antiviral compounds against dengue and West Nile virus.

Biography

Christoph Nitsche studied chemistry and business administration. He obtained his Ph.D. on the development of dengue virus protease inhibitors under the guidance of Prof. Christian Klein at Heidelberg University with a scholarship from the German National Academic Foundation. Currently, he is working as a Feodor Lynen Fellow (Alexander von Humboldt-Foundation) in the laboratory of Prof. Gottfried Otting at the Australian National University. His present research focuses on novel NMR methods for drug discovery.

Biography

Veaceslav Boldescu studied pharmaceutical technology and obtained a Ph.D. in Technology of special products (pharmaceuticals) in 2008 under the guidance of Acad. Gheorghe Duca (Academy of Sciences of Moldova). He started his research pathway at the State University of Moldova and continued it at the Institute of Chemistry of the Academy of Sciences of Moldova, working in the Laboratory of Organic Synthesis lead by Prof. Fliur Macaev. His main research interests include development of new chemotherapeutic agents against infections such as tuberculosis and dengue.

Biography

Christian D. Klein studied pharmacy and obtained a Ph.D. in Pharmaceutical Chemistry in 2000 under the guidance of Profs. Ulrike Holzgrabe (University of Bonn) and A. J. Hopfinger (UIC, Chicago). Following postdoctoral work at ETH Zürich, he became an Emmy Noether junior group leader. Since 2007, he is professor of Pharmaceutical Chemistry at Heidelberg University. His main research interests are anti-infective compounds and fundamental questions in medicinal chemistry, such as the study of unusual binding modes and structural motifs.

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Continuous ruthenium-catalyzed methoxycarbonylation with supercritical carbon dioxide

Catal. Sci. Technol., 2016, Advance Article
DOI: 10.1039/C5CY01883H, Paper

Stefan Christiaan Stouten, Timothy Noel, Qi Wang, Matthias Beller, Volker Hessel
The methoxycarbonylation of cyclohexene with carbon dioxide over a ruthenium catalyst was realized in a micro flow system under supercritical conditions.

Continuous ruthenium-catalyzed methoxycarbonylation with supercritical carbon dioxide

http://pubs.rsc.org/en/Content/ArticleLanding/2016/CY/C5CY01883H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2Fcy+%28RSC+-+Catalysis+Science+%26+Technology+latest+articles%29#!divAbstract

The methoxycarbonylation of cyclohexene with carbon dioxide over a ruthenium catalyst was realized in a micro flow system under supercritical conditions. Instead of the toxic and flammable carbon monoxide, this process utilizes carbon dioxide, thereby avoiding issues with bulk transportation of carbon monoxide as well as eliminating the need for safety precautions associated with the use of carbon monoxide. Obtained was a 77% yield of the ester product at 180 °C, 120 bar and with a 90 min residence time, which is over five times faster than for the same reaction performed under subcritical conditions in batch. An important factor for the performance of the system was to have a sufficiently polar supercritical mixture, allowing the catalyst to dissolve well. The optimal temperature for the reaction was 180 °C, as the activity of the system dropped considerably at higher temperatures, most likely due to catalyst deactivation.

Department of Chemical Engineering and Chemistry

ir. S.C. (Stefan) Stouten –

Address:

Technische Universiteit Eindhoven
P.O. Box 513
5600 MB EINDHOVEN

Department:

Department of Chemical Engineering and Chemistry

Section:

Micro Flow Chemistry and Process Technology

Positioncategory:

doctoral candidate (PhD) (PhD Stud.)

Position:

doctoral candidate

Room:

STW 0.

Email:

s.stouten@tue.nl

Volker Hessel

prof.dr. V. (Volker) Hessel

Address:

Technische Universiteit Eindhoven
P.O. Box 513
5600 MB EINDHOVEN

Chair:

Micro Flow Chemistry and Process Technology

Department:

Department of Chemical Engineering and Chemistry

Section:

Micro Flow Chemistry and Process Technology

Positioncategory:

Professor (HGL)

Position:

Full Professor

Room:

STW 1.45

Tel:

+31 40-247 2973

Tel (internal):

2973

Email:

v.hessel@tue.nl

////////Continuous,  ruthenium-catalyzed,  methoxycarbonylation, supercritical carbon dioxide, flow reactor