DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Worlddrugtracker, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his PhD from ICT ,1991, Mumbai, India, in Organic chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA as ADVISOR earlier GLENMARK LS Research centre as consultant,Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Prior to joining Glenmark, he worked with major multinationals like Hoechst Marion Roussel, now sSanofi, Searle India ltd, now Rpg lifesciences, etc. he is now helping millions, has million hits on google on all organic chemistry websites. His New Drug Approvals, Green Chemistry International, Eurekamoments in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 year tenure, good knowledge of IPM, GMP, Regulatory aspects, he has several international drug patents published worldwide . He gas good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, polymorphism etc He suffered a paralytic stroke in dec 2007 and is bound to a wheelchair, this seems to have injected feul in him to help chemists around the world, he is more active than before and is pushing boundaries, he has one lakh connections on all networking sites, He makes himself available to all, contact him on +91 9323115463, amcrasto@gmail.com

Transition-Metal-Free Cross-Coupling of Aryl and Heteroaryl Thiols with Arylzinc Reagents

spectroscopy, SYNTHESIS, Uncategorized Comments Off

Nov 092017

Zhong-Xia WANG

N,N-dimethyl-4-biphenylamine

(1) N,N-dimethyl-[1,1′-biphenyl]-4-amine (3a) 5,6

Elute: EtOAc/petroleum ether: 1/100 (v/v), white solid, yield 97.8 mg (99%).

1H NMR (400 MHz, CDCl3): δ 7.56 (d, J = 7.8 Hz, 2H), 7.51 (d, J = 8.8 Hz, 2H), 7.40 (t, J = 7.7 Hz, 2H), 7.30–7.21 (m, 1H), 6.81 (d, J = 8.8 Hz, 2H), 3.00 (s, 6H).

13C NMR (101 MHz, CDCl3): δ 150.09, 141.34, 129.37, 128.78, 127.84, 126.43, 126.12, 112.90, 40.97.

5 Yang, X.; Wang, Z.-X. Organometallics 2014, 33, 5863.

(6) Stibingerova, I.; Voltrova, S.; Kocova, S.; Lindale, M.; Srogl, J. Org. Lett. 2016, 18, 312.

Transition-Metal-Free Cross-Coupling of Aryl and Heteroaryl Thiols with Arylzinc Reagents

Bo Yang^† and Zhong-Xia Wang^*^†^‡

^† CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China

^‡ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, P. R. China

Org. Lett., Article ASAP

DOI: 10.1021/acs.orglett.7b03145

*E-mail: zxwang@ustc.edu.cn.

Abstract

Cross-coupling of (hetero)arylthiols with arylzinc reagents via C–S cleavage was performed under transition-metal-free conditions. The reaction displays a wide scope of substrates and high functional-group tolerance. Electron-rich and -deficient (hetero)arylthiols and arylzinc reagents can be employed in this transformation. Mg²⁺ and Li⁺ ions were demonstrated to facilitate the reaction.

In summary, we developed a transition-metal-free coupling reaction of (hetero)arylthiols with arylzinc reagents to form bi(hetero)aryls. The reaction exhibited wide substrate scope and good compatibility of functional groups. Electron-rich and -poor aryl or heteroaryl thiols can be converted. Various arylzinc reagents, including electron-rich and electron-poor reagents, can be employed as the coupling partners. Preliminary mechanistic studies suggest a nucleophilic aromatic substitution pathway, and Mg²⁺ and Li⁺ ions play important roles in the process of reaction. This study provides an example of S^2– as a leaving group in an aromatic system and an effective methodology for the synthesis of bi(hetero)aryls including pharmaceutical molecules without transition-metal impurities.

Zhong-Xia WANG


	Department：	Department of Chemistry
	Mailing Address：	Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Rd, Hefei, Anhui, 230026, PR China
	Postal Code：	230026
	Phone：	+86-551-63603043
	Fax：
	Homepage：	http://chem.ustc.edu.cn/szdw_16/bd/201210/t20121023_142877.html

Zhong-Xia Wang is a professor in the Department of Chemistry at the University of Science and Technology 
of China. He received his BS degree (1983) and MS degree (1986) from Nankai University, 
and PhD degree (1997) from the University of Sussex, UK. Since July 1986, Wang has been working 
at the University of Science and Technology of China (USTC) successively as Assistant, 
Lecturer, Associate Professor, and Professor. From Aug. 1993 to Oct. 1996, he pursued his doctoral 
studies at the University of Sussex, UK, and from Oct. 1999 to Oct. 2000, he was a Research Associate 
at the Chinese University of Hong Kong.

 学 系
Department of Chemistry

Predicts

////////////

http://pubs.acs.org/doi/10.1021/acs.orglett.7b03145

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Benzisoxazole: a privileged scaffold for medicinal chemistry

new drugs, organic chemistry, SYNTHESIS, Uncategorized Comments Off

Nov 082017

Benzisoxazole: a privileged scaffold for medicinal chemistry

Med. Chem. Commun., 2017, Advance Article
DOI: 10.1039/C7MD00449D, Review Article

K. P. Rakesh, C. S. Shantharam, M. B. Sridhara, H. M. Manukumar, Hua-Li Qin
The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds.

Benzisoxazole: a privileged scaffold for medicinal chemistry

K. P. Rakesh,^a C. S. Shantharam,*^b M. B. Sridhara,^c H. M. Manukumar^d and Hua-Li Qin*^a

*Corresponding authors

^aDepartment of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, PR China
E-mail:qinhuali@whut.edu.cn
Fax: +86 27 87749300

^bDepartment of Chemistry, Pooja Bhagavath Memorial Mahajana Education Centre, Mysuru-570016, India
E-mail:shantharamcs@gmail.com
Tel: +91 8904386977

^cDepartment of Chemistry, Rani Channamma University, Vidyasangama, Belagavi-591156, India

^dDepartment of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysuru-570006, India

Abstract

The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds. The unique benzisoxazole scaffold also exhibits an impressive potential as antimicrobial, anticancer, anti-inflammatory, anti-glycation agents and so on. This review examines the state of the art in medicinal chemistry as it relates to the comprehensive and general summary of the different benzisoxazole analogs, their use as starting building blocks of multifarious architectures on scales sufficient to drive human drug trials. The number of reports describing benzisoxazole-containing highly active compounds leads to the expectation that this scaffold will further emerge as a potential candidate in the field of drug discovery.

Hua-Li Qin

Dr. Hua-Li Qin Ph. D 2009
qinhuali@bu.edu

Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, PR China

Hua-Li joined the Panek group in 2005.

B.S. Chemistry Engineering 2000
M.S. Chemistry 2004 University of Science & Technology of China

C. S. Shantharam

M.Sc., Ph.D

Assistant professor

Pooja Bhagavat Memorial Mahaja… , Mysore · Department of Chemistry

Department of Chemistry, Pooja Bhagavath Memorial Mahajana Education Centre, Mysuru-570016, India

Hua-Li Qin

Manukumar H M

Master of Science

Research Scholar

University of Mysore , Mysore · Department of Biotechnology

////////////Benzisoxazole, scaffold, medicinal chemistry

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Metal-free synthesis of polysubstituted pyrroles using surfactants in aqueous medium

organic chemistry, SYNTHESIS Comments Off

Nov 072017

Metal-free synthesis of polysubstituted pyrroles using surfactants in aqueous medium

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01874F, Communication

Amrendra Kumar, Ramanand, Narender Tadigoppula
An efficient and metal-free method has been developed for the synthesis of polysubstituted pyrrole derivatives with combination of sodium dodecyl sulphate (SDS) and Triton X-100 surfactants using water as a solvent at room temperature in 2-6 h and under microwave conditions (10 min) with good to excellent yields.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC01874F?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Metal-free synthesis of polysubstituted pyrroles using surfactants in aqueous medium

Amrendra Kumar,^a Ramanand^a and Narender Tadigoppula*^a

*Corresponding authors

^aMedicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow-226 031, India
E-mail: t_narendra@cdri.res.in
Tel: +91-522-2772450 Ext: 4737

Dr. Narender Tadigoppula

Principal Scientist
Medicinal & Process Chemistry
Central Drug Research Institute
India

Dr. Narender Tadigoppula is currently principal scientist in the department of medicine chemistry central drug research institute. He published more than 30 research articles. His major major research activities are identification of biologically active lead molecules through activity guided fraction and isolation work on the medicinal plants, marine organisms and microorganisms for metabolic diseases (hyperglycemia, dyslipidemia), parasitic diseases (leishmania and malaria), cancer etc., and chemical transformation of natural products of biological importance to improve their potency. We synthesize these biologically active lead molecules and their analogues in our laboratory. We have identified several lead molecules from the Indian medicinal plants for various disease areas as described below and further work is in progress to develop natural products based drugs.

Abstract

An efficient and metal-free method has been developed for the synthesis of polysubstituted pyrrole derivatives via intermolecular cycloaddition of substituted 1-phenyl-2-(phenylamino)-ethan-1-one/1-phenyl-2-(phenylamino)-propan-1-ones/2-((4-methoxyphenyl)amino)-1-(thiophen-2-yl)ethan-1-one/1-(furan-2-yl)-2-((4-methoxyphenyl)amino)ethan-1-one/1-(benzofuran-3-yl)-2-((4-methoxyphenyl)amino)ethan-1-one and dialkyl acetylene dicarboxylate/ethylbutynoate in the presence of a combination of sodium dodecyl sulphate (SDS) and Triton X-100 surfactants using water as a solvent at room temperature in 2–6 h under microwave conditions (10 min) with good to excellent yields.

Diethyl-1-(4-methoxyphenyl)-4-(p-tolyl)-1H-pyrrole 2,3dicarboxylate

white solid, yield 77%, mp 128-130 ;

1H NMR (400 MHz, CDCl3) δ 7.38(d, J = 8.2,2H), 7.31 (d, J = 7.9, 2H), 7.21 (d, J = 7.12, 2H), 6.99-6.96 (m, 3H), 4.31 (q, J = 7.2 Hz, 2H), 4.12 (q, J = 7.6Hz, 2H), 3.88 (s, 3H), 2.38 (s, 3H), 1.31 (t, J = 7.9Hz, 3H), 1.19 (t, J = 7.5Hz, 3H) ;

13C NMR (100 MHz, CDCl3) δ 166.3, 159.9, 149.0, 148.8, 136.7, 132.6, 130.3, 129.2, 127.6, 125.8, 124.5, 123.4, 121.5, 118.3, 110.5, 110.2, 61.2, 60.7, 56.0, 21.1, 14.0, 13.9.

IR (KBr) ṽ (cm-1): 2981.9, 1717.9, 1514.1, 1419.2, 1381.3, 1245.0, 1175.9, 1226.7, 1043.6, 835.7, 755.3, 663.

HRESIMS: m/zcalcd for [M+H]+ C24H26NO5 408.1805 found 408.1845.

/////////////

O=C(OCC)c2c(c(cn2c1ccc(OC)cc1)c3ccc(C)cc3)C(=O)OCC

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite

spectroscopy, SYNTHESIS, Uncategorized Comments Off

Nov 032017

Image result for Kalpana C. Maheria sv

1-benzyl-2, 4, 5-triphenyl-1H-imidazole

. 1-Benzyl-2,4,5-triphenyl-1H-imidazole (5a, n = 1).

Off-white solid; m.p.: 160–162 °C;

anal. calcd. for C28H22N2: C, 87.01, H, 5.74, N, 7.25%. Found: C, 87.13, H, 5.70, N, 7.19%;

UV (λmax, ethanol) = 280 nm;

FT-IR (KBr, cm−1 ): 3060 (C–H stretch), 3031, 1600 (CN), 1497, 1483, 1447 (CC), 1352 (C–N stretch), 769, 697 (C–H band);

1 H NMR (400 MHz, DMSO): 5.16 (s, 2H, CH2), 6.74–7.67 (m, 20H, Ar–H) ppm;

13C NMR (100 MHz, DMSO): 47.6 (CH2, C8), 125.1 (CHarom, C28), 126.0 (CHarom, C26), 126.2 (CHarom, C30), 126.4 (CHarom, C11), 127.0 (CHarom, C15), 127.1 (CHarom, C16), 127.7 (CHarom, C20), 128.0 (CHarom, C21), 128.1 (CHarom, C25), 128.4 (CHarom, C13), 128.5 (CHarom, C18), 128.6 (CHarom, C27), 128.8 (C1), 128.8 (CHarom, C12), 128.9 (CHarom, C14), 130.1 (CHarom, C17), 130.3 (CHarom, C19), 130.5 (CHarom, C22), 130.7 (CHarom, C24), 131.0 (CHarom, C29), 134.4 (CHarom, C9), 135.1 (CHarom, C23), 136.8 (CHarom, C7), 137.0 (CHarom, C10), 137.2 (CHarom, C6), 145.4 (C2), 147.0 (C4) ppm;

MS: m/z = 387.5 (M + H)+

An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: effect of surface acidity and polarity of zeolite

Jenifer J. Gabla,^a Sunil R. Mistry^b and Kalpana C. Maheria*^a

Jenifer J Gabla

S V National Institute of Technology, India

Jenifer J Gabla has obtained her MSc degree in Organic Chemistry, in the year 2013 from Uka Tarsadia University, Bardoli, Gujarat. She is currently pursuing her PhD in the area of solid acid catalyzed multicomponent reactions for the synthesis of biologically active drug molecules, at Applied Chemistry Department (ACD), S. V. National Institute of Technology (SVNIT) under the guidance of Kalpana Maheria, Assistant Professor & Head, ACD, SVNIT, Surat, Gujarat, India. Her research focuses on development of novel zeolite based catalytic materials and exploring their utility in the green process development for the synthesis of medicinal compounds. She has presented her research in several national and international conferences.

Kalpana C. Maheria

*Corresponding authors

^aApplied Chemistry Department, S. V. National Institute of Technology, Ichchhanath, Surat – 395007, India
E-mail:kcmaheria@gmail.com

^bMandvi Science College, Mandvi – 394160, Surat, India

Abstract

In the present study, the catalytic activity of various medium (H-ZSM-5) and large pore (H-BEA, H-Y, H-MOR) zeolites were studied as solid acid catalysts. The zeolite H-BEA is found to be an efficient catalyst for the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles through one-pot, 4-component reaction (4-CR) between benzil, NH₄OAc, substituted aromatic aldehydes and benzyl amine. The hydrophobicity, Si/Al ratio and acidic properties of zeolite BEA were well improved by controlled dealumination. The synthesized materials were characterized by various characterization techniques such as XRD, ICP-OES, BET, NH₃-TPD, FT-IR, pyridine FT-IR, ²⁷Al and ¹H MAS NMR. It has been observed that the dealumination of the parent zeolite H-BEA (12) results in the enhanced strength of Brønsted acidity up to a certain Si/Al ratio which is attributed to the inductive effect of Lewis acidic EFAl species, leading to the higher activity of the zeolite BEA (15) catalyst towards the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles under thermal solvent-free conditions with good to excellent yields. Using the present catalytic synthetic protocol, diverse tetra-substituted imidazoles, which are among the significant biologically active scaffolds, were synthesized in high yield within a shorter reaction time. The effect of polarity, surface acidity and extra framework Al species of the catalysts has been well demonstrated by means of pyridine FT-IR, and ²⁷Al and ¹H MAS NMR. The solvent-free synthetic protocol makes the process environmentally benign and economically viable.

Image result for S. V. National Institute of Technology, Ichchhanath, Surat

S. V. National Institute of Technology, Ichchhanath, Surat

Mandvi Science College, Mandvi – 394160, Surat, India

////////

DISCLAIMER

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

Design and evolution of the BMS process greenness scorecard

green chemistry Comments Off

Oct 312017

Design and evolution of the BMS process greenness scorecard

Green Chem., 2017, 19,5163-5171
DOI: 10.1039/C7GC02190A, Paper

David K. Leahy, Eric M. Simmons, Victor Hung, Jason T. Sweeney, William F. Fleming, Melanie Miller
A process greenness scorecard has been developed that provides a comprehensive assessment of greenness aspects not encompassed by mass-based metrics, including environmental, health and safety impacts, in order to facilitate the design of greener, more benign and inherently safer processes.
The content of this RSS Feed (c) The Royal Society of Chemistry

Melanie Miller

Executive Director, Pharmaceutical Development at Bristol Myers Squibb

Head of API Operations, Pharmaceutical Development

Bristol Myers Squibb

New Brunswick, New Jersey

Leads manufacturing operations to deliver small molecule active pharmaceutical ingredients for investigational medicines. Scope includes all R&D API manufacturing operations within a global external and internal manufacturing network supporting delivery of small molecules, antibody-drug conjugates, peptides and oligonucleotides.

Design and evolution of the BMS process greenness scorecard

David K. Leahy,*^a Eric M. Simmons,*^a Victor Hung,^b Jason T. Sweeney,^c William F. Fleming^d and Melanie Miller^b

*Corresponding authors

^aChemical and Synthetic Development, Bristol-Myers Squibb, New Brunswick, USA
E-mail:eric.simmons@bms.com

^bAPI Operations, Bristol-Myers Squibb, New Brunswick, USA

^cDrug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, USA

^dEnvironmental Health Safety and Sustainability, Bristol-Myers Squibb, East Syracuse, USA

Jason Sweeney

Associate Director at Bristol-Myers Squibb

Abstract

An accurate and comprehensive assessment of the environmental, health and safety impacts of a chemical process is critical to the design and implementation of greener, more benign and inherently safer processes. Over the past 15 years at BMS, we have developed a Process Greenness Scorecard to capture and analyse a number of metrics and attributes for each step in the synthetic sequence used to produce an API. This manuscript describes the design and evolution of the scoring methodology and implementation of the resulting scorecard, from an initial Excel-based tool to the current web-based format.

David K. Leahy

https://www.linkedin.com/in/davidkleahy/

Associate Director, Process Chemistry

Company NameTakeda

Dates EmployedJul 2017 – Present

Employment Duration4 mos

LocationCambridge, MA
Principal Scientist

Company NameBristol-Myers Squibb

Dates Employed2013 – 2017

Employment Duration4 yrs

LocationGreater New York City Area

• Project leader for two high priority small molecule oncology programs, delivering preclinical supplies for five separate analogues (three separate chemotypes) at an external CMO at least one month prior to candidate nomination. Developed a new chemical route for the most complex analogue to overcome poor efficiency (key fragment improved from 1.4% yield in 8 steps to 33% yield in 5 steps).
• Chemistry lead for a highly accelerated oncology program, responsible for the late-phase development and external execution of three complex regulatory starting materials. Invented a new synthetic route to circumvent a key scale-up liability, while removing numerous bottlenecks.
• Project leader for a biologics/small molecule conjugate PET tracer. Developed bio-orthogonal chemistry to prepare and purify the cold PET tracer analogue needed for IND toxicology studies. Key thought leader in developing new CMC strategies utilized by subsequent PET tracer teams.
• CMC leader for diabetes and fibrosis assets. Led cross-functional CMC team and Exploratory Development team through a very complex tautomer challenge. Strategically laid out and executed plans demonstrating that the tautomers posed no risk to patient safety and effectively communicated this to the FDA. Guided team to achieve key program milestone of First in Human.
• Co-invented a novel, non-chromatographic approach to purification of macro-cyclic peptides.
• Co-chair of the ACS Green Chemistry Institute Pharmaceutical Roundtable, responsible for implementation of strategic priorities and management of a $375k budget.
• Team lead for BMS corporate sustainability 2015 and 2020 goals to integrate sustainability throughout development and commercialization.
• Supervision of Ph.D. level direct reports. Committed to the professional development of project teams and direct reports, helping refine their skills, obtain promotions, and identify new roles that meet their career aspirations and passion.

Introduction

“The ability to meet the needs of the present without compromising the ability of future generations to meet their needs” The definition of sustainable development from the United Nations World Commission on Environment and Development has indeed resonated with corporate leaders across the globe.1 This is evident by the wealth of public-facing sustainability goals that Fortune 500 companies have committed to over the last decade. Within the context of the pharmaceutical industry, it is green chemistry2 that provides the key to environmentally-responsible pharmaceutical manufacturing3 , and practitioners have been rewarded with enormous impacts to their triple bottom line.4

Green chemistry is more cost-effective, safer for employees, and better for the environment. Corporate sustainability has been characterized as a key driver for innovation, which is essential for a firm to succeed.5 As part of our program in green chemistry, we anticipated that a tool that could assess the ‘greenness’ of our chemical processes would spark the innovation of our scientists, by pointing out deficient areas, prompting focus on these areas, and providing quantitative evidence that their improvements had the desired impact.6

A number of mass-based metrics are available to assess the greenness of a chemical process,7,8 with E factor (kg of waste/kg of product)9 and Process Mass Intensity (PMI = kg of inputs/kg of product)10 being most widely utilized within the pharmaceutical industry.7,8,10 We firmly believe that such metrics are very important, but we also recognized that they ignore many key green chemistry principles, most importantly safety.7,11,12

While important strides have been made in the development of quantitative methods to compare the environmental impact of chemical syntheses,13 most notably though Life Cycle Assessment (LCA)14 and the FLASC tool,15 as well as the recently introduced Green Aspiration Level (GAL),7,12 metrics that assess the safety and health hazards of chemical processes and products are lacking in comparison.16,17

In this article, we describe the strategy we have taken at Bristol-Myers Squibb to expand on existing mass-based approaches to include a comprehensive assessment of the important facets of greenness not encompassed by typical process metrics, such as E factor and PMI, to develop a Process Greenness scoring methodology that is appropriate for the assessment of the chemical processes used on scale for the synthesis of smallmolecule active pharmaceutical ingredients (APIs) and intermediates.18,19

Eric Simmons

Senior Research Investigator II at Bristol-Myers Squibb

Conclusions

The BMS process greenness scorecard is an important tool for scientists to help guide decisions made during API process development. It serves as the key methodology we use to assess the environmental and safety performance of our processes to manufacture compounds in development. This greenness score provides a useful and quantitative method, complimentary to mass based metrics such as PMI and derived from the 12 principles of green chemistry. A key advantage of this assessment is that it also considers the inherent safety of a process, both from a worker exposure and process hazards perspective. These are key green chemistry considerations that are not captured when evaluating a process using mass-based metrics alone. This assessment is especially important when facing complex decisions involving tradeoffs between improved efficiency versus enhanced process safety. While this tool is currently only suitable for use in evaluating small molecules, efforts are underway to expand this methodology to assess other important therapeutic modalities, including synthetic peptides, oligonucleotides, antibody-drug conjugates, and biologics and will be reported in due course.

William Fleming

Director, Head of Safety, Global EHS&S

Bristol-Myers Squibb

Chemical and Synthetic Development, Bristol-Myers Squibb, New Brunswick, USA

////////////////Bristol-Myers Squibb, bms, green

ref http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02190A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

more…………..

DOI: 10.1039/C6GC02359B (Paper) Green Chem., 2017, 19, 127-139

A data-driven strategy for predicting greenness scores, rationally comparing synthetic routes and benchmarking PMI outcomes for the synthesis of molecules in the pharmaceutical industry†

Jun Li , Eric M. Simmons and Martin D. Eastgate *
Chemical and Synthetic Development, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903, USA. E-mail: martin.eastgate@bms.com

Apixaban: Our final case study is apixaban (45), an orally bioavailable inhibitor of blood coagulation factor Xa, developed for thrombotic diseases and commercialized as Eliquis (Scheme 6).¹⁷ This highly optimized process evolved through multiple rounds of development and the data reported is taken from the validation campaign, thus ready for product launch. The actual cumulative PMI for the overall process was 197, which is significantly below the lower end of the 95% confidence interval for the predicted cumulative PMI (Fig. 14). In essence, it is lower than 99.9% of the similar chemistries executed on scale at different development stages. This is the one of a few commercial assets in our current database, and while obviously efficient, this score should be viewed with the perspective that most of the data available to us in this proof of concept study is in the development phase, and thus encompasses a wide range of optimization levels. However, in order to compare more globally, more data, from more companies, and across all phases of development is needed.


	Scheme 6 Apixaban synthetic route in validation campaign.

Fig. 14 Predicted apixaban cumulative PMI with mean 366 and 95% CI between 261 and 480.

image file: c6gc02359b-f14.tif

Dimethyl carbonate: a versatile reagent for a sustainable valorization of renewables

Uncategorized Comments Off

Oct 262017

Dimethyl carbonate: a versatile reagent for a sustainable valorization of renewables

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC02118F, Critical Review

G. Fiorani, A. Perosa, M. Selva
Green upgrading of renewables via methylations and carboxymethylations with non-toxic dimethyl carbonate (DMC).

Dimethyl carbonate: a versatile reagent for a sustainable valorization of renewables

G. Fiorani,^a A. Perosa^b and M. Selva*^b

Author affiliations

*Corresponding authors

^aDepartment of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK

^bDepartment of Molecular Sciences and Nanosystems, Ca’ Foscari University of Venice, Via Torino 155, 30172 Venezia Mestre, Italy
E-mail:selva@unive.it

Giulia Fiorani

Postdoctoral Research Fellow presso University of Oxford

Dr. Fiorani earned her PhD in Chemical Sciences from the University of Rome “Tor Vergata” (2010) on synthesis and applications of ionic liquids. After several post-doctoral experiences (University of Padua, Italy 2010-2012, Ca’ Foscari University of Venice 2012-2013), Giulia was awarded a Marie Curie Intra-European Fellow in 2014 at ICIQ (Institute of Chemical Research of Catalonia, Tarragona, Spain) working under the supervision of Prof. Arjan W. Kleij on the preparation of cyclic organic carbonates from CO2 and terpene based oxiranes. Giulia joined the Williams group in 2016 and is working on renewable based polymers.

Abstract

Dimethyl carbonate (DMC) is an environmentally sustainable compound which can be used efficiently for the upgrading of several promising renewables including glycerol, triglycerides, fatty acids, polysaccharides, sugar-derived platform molecules and lignin-based phenolic compounds. This review showcases a thorough overview of the main reactions where DMC acts as a methylating and/or methoxycarbonylating agent for the transformation of small bio-based molecules as well as for the synthesis of biopolymers. All processes exemplify genuine green archetypes since they couple innocuous reactants of renewable origin with non-toxic DMC. Each section of the review provides a detailed overview on reaction conditions and scope of the investigated reactions, and discusses the rationale behind the choice of catalyst(s) and the proposed mechanisms. Criticism and comments have been put forward on the pros and cons of the described methods and their perspectives, as well as on those studies which still require follow-ups and more in-depth analyses.

Giulia Fiorani

Ph. D. in Chemical Sciences

Post Doctoral Research Assistant

University of Oxford , Oxford · Department of Chemistry

Research experience

Sep 2016–present

Post Doctoral Research Assistant

University of Oxford · Department of Chemistry · Prof. Charlotte K. Williams

United Kingdom

Polymer chemistry and catalysis applied to polymers preparation.
Mar 2016–Sep 2016

Post Doctoral Research Assistant

Imperial College London · Department of Materials · Prof. Charlotte K. Williams

United Kingdom · London, England

Polymer chemistry and catalysis applied to polymers preparation.
Mar 2014–Feb 2016

Marie Curie Intra-European Fellow

ICIQ Institute of Chemical Research of Catalonia · Prof. Arjan W. Kleij

Spain

Novel applications of renewable based molecules for the preparation of cyclic carbonate and polycarbonates (FP7-PEOPLE-2013-IEF, project RENOVACARB, Grant Agreement no. 622587).
Apr 2012–Oct 2013

Post Doctoral Research Assistant

Università Ca’ Foscari Venezia · Department of Molecular Science and Nanosystems · Prof. Maurizio Selva, Prof. Alvise Benedetti

Italy

Synthesis and characterization of luminescent Ionic Liquids.
Jan 2011–Feb 2012

Post Doctoral Research Assistant

Italian National Research Council · Institute on Membrane Technology ITM · Prof. Marcella Bonchio, Dr Alberto Figoli

Italy · Rome

Project BioNexGen – development of a new generation of membrane reactors.
Jan 2010–Dec 2010

Research Assistant

University of Padova · Department of Chemical Sciences · Dr Mauro Carraro

Italy · Padova

Hybrid nanostructures organized by hybrid ligands for the preparation of new functional materials.

Teaching experience

Sep 2016–Oct 2016

Visiting Scholar

Università degli Studi di Sassari · Department of Chemistry and Pharmacy

Italy · Sassari

10 hour course on terpene chemistry for PhD students.

Education

Nov 2006–Mar 2010

University of Rome Tor Vergata

Chemical Sciences · PhD

Italy
Oct 2004–Jul 2006

University of Rome Tor Vergata

Chemistry · Master of Science

Italy
Sep 2001–Oct 2004

University of Rome Tor Vergata

Chemistry · BSc

Italy

Other

Languages

English, Italian, Spanish
Scientific Societies

Member of the Italian Chemical Society since 2007.

PEROSA Alvise

Qualifica	Professore Associato
Telefono	041 234 8958
E-mail	alvise@unive.it
Fax	041 234 8979
Web	www.unive.it/persone/alvise (scheda personale) http://venus.unive.it/alvise/
Struttura	Dipartimento di Scienze Molecolari e Nanosistemi Sito web struttura: http://www.unive.it/dsmn Sede: Campus scientifico via Torino
Research team	Environmental technology and green economy
Research team	Science of complex economic, human and natural systems
Incarichi	Delegato per il Dipartimento all’Internazionalizzazion

logo unive

Currently: Associate professor of Organic Chemistry with tenure.

Department of Molecular Sciences and Nanosystems, University Ca’ Foscari Venice.

Born in Venice in 1965. Married to Paola, two children: Alberto (2000) and Marta (2002).

Career

– 2011, was offered the senior position as Associate professor of Chemistry with Tenure at UMAss Boston.

– 2005-2014 Assistant professor of Organic Chemistry with tenure (SSD CHIM/06), University Ca’ Foscari Venice.

– 2007 Visiting scientist, University of Sydney.

– 1996-2005 Post-doctoral researcher University Ca’ Foscari Venice.

Education

– 1996 Ph.D. in Chemistry, Case Western Reserve University, Cleveland OH, USA.

– 1992 Laurea in Industrial Chemistry @ University Ca’ Foscari Venice.

Fellowships

– 2007 Endeavour Research Fellow (Austrlian Government, Department of Education, Employment and Workplace Relations) at the University of Sydney.

– 1992-1996 Fulbright Fellow (U.S. Department of State, International Educational Exchange Program) at Case Western Reserve University.

– 1993 CNR Research Fellow (1993) at Case Western Reserve University, Cleveland OH, USA.

Awards

– Ca’ Foscari Research Prize (2014, category Advanced Research).

– Royal Society of Chemistry International Journal Grants Awards (2007, 2009).

– CNR prize for research (1994).

– Outstanding teaching award CWRU (1993).

– Prize for the Laurea thesis from the Consorzio Venezia Ricerche (1992).

Editorial Board memberships

– Advisory Board of the journal “Green Chemistry” (Royal Society of Chemistry, UK).

– Editorial Advisory Board of the journal “ACS Sustainable Chemistry and Engineering” (American Chemical Society, USA).

Training and editorial activities.

– Scientific coordinator and organizer of the Summer School on Green Chemistry from 1998 to 2006 (funded by the European Commission, UNESCO, and NATO).

– Editor of the volume “Methods and Reagents for Green Chemistry” Wiley Interscience 2007.

– Editor of “Green Nanoscience”, volume 8 of the 12 volume set of the “Handbook of Green Chemistry” P. Anastas Ed., Wiley-VCH 2011.

– Author of over 60 scientific papers and chapters and of one patent in the field of organic chsmistry, with emphasis on green chemistry. Hirsch index (Scopus, Feb. 2014) = 21.

Invited talks

– Green chemistry applied to the upgrading of bio-based chemicals: towards sustainable chemical production. University of Sydney, 19 March 2014.

– Sustainable (Chemical) Solutions, Rethinking Nature in Contemporary Japan, Università Ca’ Foscari, Venezia, 25-26 February 2013

– Carbonate based ionic liquids and beyond, Green Solvents Conference, Frankfurt am Main, Dechema Gesellschaft fur Chemische Technik und Biotechnologie e. V., pp. 27, Green Solvents for Synthesis, Boppard, 8-10 Ottobre 2012

– Chemicals e Fuels da Fonti Rinnovabili, Bioforum. Biotecnologie: dove scienza e impresa si incontrano, Milano, ITER, vol. VII Edizione, Bioforum, Confindustria Venezia, 24.02.2011

– Green Chemistry for Sustainability: Teaching ionic liquids new tricks & A breath of oxygen for bio-based chemicals., Slovenian-Italian conference on Materials and Technologies for Sustainable Growth, Ajdovscina, Slovenia, 4-6 Maggio 2011

– Benign molecular design, WORKSHOP ON ECOPHARMACOVIGILANCE, Verona, 26-27 Marzo 2009

– Not merely solvents: task specific ionic liquids made by green syntheses, COIL-3 Pre-symposium workshop, Cairns, Australia, 31/05/2009

– Multiphase catalysis: a tool for green organic synthesis, Royal Australian Chemical Institute NSW Organic Chemistry Group, 28th Annual One-Day Symposium, MacQuarie University, Sydney, Australia, 5 December 2007

– Catalytic Reactions in Liquid Multiphasic Systems The acronym talk, INTAS Project on POPs, Moscow, 12-14 Giugno 2005

– Catalytic reactions in liquid multiphasic systems, Convegno: Eurogreenpol – First European Summer School on Green Chemistry of Polymers, Iasi – Rumania, 21-27 Agosto 2005

– Multiphase hydrodehalogenation reactions, RWTH Aachen – Germany, 12 Febbraio 2003

– Mechanism and Synthetic Applications of the Multiphase Catalytic Systems, International Workshop on Hazardous Halo-Aromatic Pollutants: Detoxification and Analysis, Venezia, 14-16 Maggio 2002

– The multiphase catalytic hydrodehalogenation of haloaromatics, European Summer School on Green Chemistry, Venezia, 10-15 September 2001

Academic committees

– Quality assurance board of Ca’ Foscari University

– Teaching council of the International College, Ca’ Foscari merit school.

– Academic Council of Venice International University VIU.

– Delegate for international relations of the Department of Molecular Sciences and Nanosystems.

– Scientific board of Edizioni Ca’ Foscari – Digital Publishing.

– Research committee of the Department of Molecular Sciences and Nanosystems.

– Teaching board of the Doctorate in Chemical Sciences (2012-2014).

– Teaching board of the degree course Bio- and Nanomaterials science and Technology.

– Erasmus selection committee.

– Overseas selection committee

– Post-doctoral selection committees.

Referee, reviewer, and examiner for:

– Valutazione della Qualità della Ricerca (VQR), ANVUR

– Progetti di Rilevante Interesse Nazionale (PRIN), MIUR

– American Chemical Society Petroleum Research Fund (USA).

– Ph.D. Theses, University of Nottingham (UK) and University of Sydney (Aus).

– European Science Foundation

– Journals published by: Royal Society of Chemistry, American Chemical Society, Wiley, Elsevier, Springer, IUPAC

Funded projects

– Coordinator of a Cooperlink project funded by the Italian Ministry for Education, University and Research, 2011, 12 months, entitled “Joint PhD between Università Ca’ Foscari and the University of Sydney: integration of experiment and theory towards the green synthesis of self-assemblying materials and the use of renewable resources”.

– Participant in the Project of Relevant National Interest (PRIN) “Green organic syntheses mediated by new catalytic systems”, 2010, 24 months.

– Tutor of a PhD scholarship funded by the Regione Veneto through the European Social Fund, entitled “Organic syntheses of active principles and chemicals for the pharmaceutical industry using green solvents “ 2009-2011, 36 months.

– Principal Scientist of a post-doctoral fellowship funded by the Regione Veneto through the European Social Fund entitled “New reduced environmental impact chemical synthesesfor the preparation of monomers for advanced polymers, April 2012, 12 months.

– Principal Scientist of a post-doctoral fellowship funded by the Regione Veneto through the European Social Fund entitled “Environmentally compatible chemical syntheses of fluorinated monomers for advanced materials” April 2013, 12 months.

– Principal Scientist of a post-doctoral fellowship funded by the Regione Veneto through the European Social Fund entitled “Valorisation of renewable substrates from biomass, such as glycerol and its derivatives, using green chemistry” April 2014, 12 Months

– Principal Scientist of a research contract between the chemical company Aussachem (Santandrà di Povegliano, TV), entitled: “Green Chemistry for the valorisation of glycerol and of its derivatives: new ecofriendly products” December 2013.

International collaborations and networks

– Teaching and research collaboration with the University of Sydney, School of Chemistry Laboratory for Advanced Catalysis and Sustainability prof. Thomas Maschmeyer. A joint PhD program in Chemistry was established and is currently running. Up to date 5 students (3 outgoing, 2 incoming) have benefited from this agreement The first joint PhD has been awarded in December 2013 (Marina Gottardo). Four joint publications have already been produced, and others are in preparation.

– Research collaboration with the Queen’s University of Belfast, Queen’s University Ionic Liquids Laboratory, prof. Kenneth R. Seddon, for the exchange of Erasmus students who carry out research towards their MS thesis. Currently the student Riccardo Zabeo is in Belfast w research towards his thesis, tutor dr. Perosa. Previously, the PhD student Marco Noè (tutor Perosa) spent 4 months in Belfast carrying out research that was published on an international journal.

– In the framework of a scientific collaboration with prof. Janet Scott of the Centre for Sustainable Chemical Technologies of the University of Bath, an Erasmus Mundus Joint Doctorate project entitled “Bio-Based Chemicals and Materials” was submitted in 2011 and was evaluated positively albeit not funded. Nonetheless the collaboration has already produced a joint publication.

– Summer School on Green Chemistry Network. Following the 8 editions of the “Summer school on Green Chemistry” (1998-2005) coordinated and organized by the applicant, a Green Chemistry Network was initiated that involves the following institutions: RWTH-Aachen, QUB-QUILL Belfast, UNSW-Sydney, ARKEMA-France, University of Groningen-NL, Dow Europe-CH, Universite de Poitiers, ETH-Zurich, TU-Darmstadt, Universidad Politecnica de Valencia, Delft University of Technology, TU-Munchen.

– Since 1993 Alvise Perosa is a member of the American Chemical Society.

MoU’s and International agreements

– Alvise Perosa started the Joint PhD degree in Chemistry between the University of Sydney and the Università Ca’ Foscari Venezia.

– Erasmus, Alvise Perosa is the contact person for the following Erasmus agreements: Universitat Autonoma de Barcelona, Universidad Rey Juan Carlos, Universidad Rovira i Virgili,UNIVERSITE D’AVIGNON ET DES PAYS DE VAUCLUSE, ARISTOTLE UNIVERSITY THESSALONIKI, Queen’s University of Belfast.

Academic tutoring

– Marco Noè (PhD 2009-11: 24° cycle)

– Jessica N. G. Stanley (PhD cotutelle University of Sydney, 2012-2014)

– Alessio Caretto (PhD 2012-14: 27° cycle)

– Manuela Facchin (PhD 2014-16: 29° cycle)

– Tutor if BSc and MSc level students of the degree corse in Sustainable Chemistry and Technologies and, and of the MSc degree course in Science and Technolgy of Bio- and Nanomaterials.

Teaching

– 1992-94, Case Western Reserve University, Chemistry BS: Organic Chemistry 1 Laboratory (teaching assistant award in 1993).

– 1997-2000, Università Ca’ Foscari Venezia, degree course in Environmental Sciences: Organic Chemistry Exercises.

– 1997-2000, Università Ca’ Foscari Venezia, degree course in Industrial Chemistry: Organic Chemistry 1 & 2 Laboratory, Industrial Chemistry 2 Exercises, Organic Chemistry 1 (part-time students) and Advanced Organic Chemistry.

– 2006-09, Università Ca’ Foscari Venezia, degree course in Chemical Sciences and Technologies for Cultural Heritage Conservation and Restoration: Organic Chemistry Laboratory.

– 2006-07, Università Ca’ Foscari Venezia, degree course in Chemistry, Industrial Chemistry, Materials Chemistry, Environmental Sciences: Organic Chemistry 1 and Laboratory for part-time students.

– 2005-06, 2011-12, 2012-13, 2013-14: Università Ca’ Foscari Venezia, degree course in Chemistry and in sustainable Chemical Technologies: Organic Chemistry 2 and Laboratory.

– 2011-12, Università Ca’ Foscari Venezia, degree course in Chemistry and in sustainable Chemical Technologies: Green Organic synthesis Laboratory.

– 2012-13, 2013-14 Università Ca’ Foscari Venezia, MS degree course in Bio e Nanomaterials: Colloids and Interfaces.

– 2013-14 Università Ca’ Foscari Venezia, Graduate course in Organic syntheses from renewable building blocks.

SELVA Maurizio

Qualifica	Professore Ordinario
Telefono	041 234 8687
E-mail	selva@unive.it
Fax	041 234 8979
Web	www.unive.it/persone/selva (scheda personale)
Struttura	Dipartimento di Scienze Molecolari e Nanosistemi Sito web struttura: http://www.unive.it/dsmn Sede: Campus scientifico via Torino

http://www.unive.it/data/persone/5591976/pubb_tipo

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http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02118F?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

A roadmap towards green packaging: the current status and future outlook for polyesters in the packaging industry

Formulation, PROCESS Comments Off

Oct 172017

A roadmap towards green packaging: the current status and future outlook for polyesters in the packaging industry

Green Chem., 2017, 19,4737-4753

DOI: 10.1039/C7GC02521A, Tutorial Review

M. Rabnawaz, I. Wyman, R. Auras, S. Cheng
Approximately 99% of the plastics used in the packaging industry today are petroleum-based. However, the adoption of biobased plastics could help to greatly reduce the environmental footprint of packaging materials and help to conserve our non-renewable petroleum resources. This tutorial review provides an overview of renewable polyesters and their potential packaging materials.

A roadmap towards green packaging: the current status and future outlook for polyesters in the packaging industry

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02521A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

M. Rabnawaz,*^a I. Wyman,^b R. Auras^a and S. Cheng^a

Author affiliations

*Corresponding authors

^aSchool of Packaging, Michigan State University, 448 Wilson Road, East Lansing, USA
E-mail:rabnawaz@msu.edu, aurasraf@anr.msu.edu, Shouyun-Cheng@hotmail.com

^bDepartment of Chemistry, Queen’s University, 90 Bader Lane, Kingston, Canada
E-mail:3iww@queensu.ca

Muhammad Rabnawaz

Assistant Professor

rabnawaz@msu.edu
Telephone: 517-432-4870

Rabnawaz’s Research Group
School of Packaging

Shouyun Cheng

Doctor of Philosophy

Research Associate

Michigan State University , East Lansing · School of Packaging

Michigan State University | MSU

School of Packaging

East Lansing, MI, United States

Dr. Cheng earned his PhD from South Dakota State University in May 2017. He has extensive research experiences in biomass pyrolysis and liquefaction, bio-oil catalytic cracking and hydrodeoxygenation, catalyst design, preparation, characterization and evaluation, food extruding, nano cellulose and protein peptides production, polymer synthesis, characterization and application.

Project Titles worked on: Innovation for Improved Sustainability: Scalable Approach for the Preparation of Thermoplastic Starches and their Composites for Applications in Biodegradable Packaging .

Duration in the group: August 2017- Present

Areas of Interest: Polycarbonates and polyesters synthesis, characterization and application.

MSU email Id: chengsho@msu.edu

Ian Wyman

Education: Ph.D., Queen’s University, Kingston, Ontario
M.Sc., St. Francis Xavier University, Antigonish, Nova Scotia
B.Sc. Chemistry, Dalhousie University, Halifax, Nova Scotia

Email: wymani@chem.queensu.ca

Abstract

Approximately 99% of the plastics produced today are petroleum-based, and the packaging industry alone consumes over 38% of these plastics. In this review, we argue that renewable polyesters can provide a key milestone as renewable plastics in the route toward green packaging. This review describes different classes of polyesters with particular regard to their potential use as packaging materials. Some of the families of polyesters discussed include poly(ethylene terephthalate) and its renewable analogs, poly(lactic acid), poly(hydroxyalkanoates), and poly(epoxy anhydrides). The synthesis of polyesters is discussed from a green chemistry perspective. A structure–property correlation among the various polyesters is also discussed. The challenges that currently hinder the widespread adoption of polyesters as leading packaging materials are reviewed. The environmental footprint and end of life scenario of polyesters are discussed. Finally, future research directions are summarized as a possible roadmap towards the widespread adoption of renewable polyesters as sustainable packaging materials.

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Muhammad Rabnawaz

Assistant Professor

rabnawaz@msu.edu
Telephone: 517-432-4870

Rabnawaz’s Research Group
School of Packaging

Research Interests

I have published more than 20 research articles in the field of polymer and materials sciences. Our initial endeavors can be divided into three broad categories:

Polymer synthesis from renewable feedstocks.
Design and preparation of smart materials.
Polymer composites.

Our projects are highly applied, and we expect close collaboration with world-leading industries. These partnerships will offer unique training and career opportunities for the group members.

Experience

Assistant Professor, School of Packaging, Michigan State University (2016-currrent)
Postdoctorate, University of Illinois, Urbana-Champaign, 2015-2016
Postdoctorate, Queen’s University, Canada, 2013-2015

Education

Ph.D., Chemistry, Queen’s University, Canada, 2013
M.Sc., Chemistry, University of Peshawar, Pakistan, 2004

Muhammad Rabnawaz

Isosorbide dimethyl ether

PROCESS, spectroscopy, SYNTHESIS Comments Off

Oct 162017

Image result for Isosorbide dimethyl ether

CAS Registry No.:	5306-85-4
Molecular Formula:	C₈H₁₄O₄	Molecular Weight:	174.2

Image result for Isosorbide dimethyl ether SYNTHESIS

13 C NMR

22.53 MHz
C₈ H₁₄ O₄	0.05 ml : 0.5 ml CDCl₃

1H NMR

IR NEAT

RAMAN

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Diethyl Isosorbide (DEI)

spectroscopy, SYNTHESIS, Uncategorized Comments Off

Oct 162017

Diethyl Isosorbide (DEI): []D 20 +95.9 (c 1, in MeOH);

1H NMR (400 MHz; CDCl3; Me4Si):  4.63 (t, J = 4.2 Hz, 1H, H-4), 4.51 (d, J = 4.1 Hz, 1H, H-3), 4.06–3.90 (m, 5H, H- 1, H-2, H-5, H-6), 3.80–3.69 (m, 1H, CH2-OC-5), 3.63–3.49 (m, 4H, H-6, CH2-OC-5, CH2- OC-2), 1.23 ppm (dt, J = 17.8, 7.0 Hz, 6H, CH3CH2O-C-2, CH3CH2O-C-5);

13C NMR (101 MHz; CDCl3; Me4Si):  86.57 (C-3), 84.45 (C-2), 80.36 (C-5), 80.27 (C-4), 73.64 (C-1), 69.81 (C-6), 66.28 (CH2-O-C-5), 65.24 (CH2-O-C-2), 15.49 ppm (CH3-CH2OC-5), 15.44 (CH3-CH2OC-2);

MS (70 eV): m/z 202 (M+ , 6%), 157 (1), 113 (17), 89 (33), 69 (100), 57 (11), 44 (39).

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Synthesis of isosorbide: an overview of challenging reactions

PROCESS, SYNTHESIS Comments Off

Oct 162017

Synthesis of isosorbide: an overview of challenging reactions

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01912B, Tutorial Review

C. Dussenne, T. Delaunay, V. Wiatz, H. Wyart, I. Suisse, M. Sauthier
This review gives an overview of the catalysts and technologies developed for the synthesis of isosorbide, a platform molecule derived from biomass (sorbitol and cellulose).

Synthesis of isosorbide: an overview of challenging reactions

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC01912B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

C. Dussenne,^a T. Delaunay,^b V. Wiatz,^c H. Wyart,^c I. Suisse^a and M. Sauthier*^a

Author affiliations

*Corresponding authors

^aUMR 8181 Unité de Catalyse et de Chimie du Solide, Université Lille Nord de France, USTL, ENSCL, Cité Scientifique, 59652 Villeneuve d’Ascq Cedex, France

^bInstitut Français des Matériaux Agro-Sourcés, Parc Scientifique de la Haute Borne, 60 Avenue du Halley, 59650 Villeneuve d’Ascq, France

^cRoquette Frères, 62080 Lestrem Cedex, France

Abstract

Isosorbide is a diol derived from sorbitol and obtained through dehydration reactions that has raised much interest in the literature over the past few decades. Thus, this platform chemical is a biobased alternative to a number of petrosourced molecules that can find applications in a large number of technical specialty fields, such as plasticizers, monomers, solvents or pharmaceuticals. The synthesis of isosorbide is still a technical challenge, as several competitive reactions must be simultaneously handled to promote a high molar yield and avoid side reactions, like degradation and polymerization. In this purpose, many studies have proposed innovative and varied methods with promising results. This review gives an overview of the synthesis strategies and catalysts developed to access this very attractive molecule, pointing out both the results obtained and the remaining issues connected to isosorbide synthesis.

Up to now, isosorbide has been used to access a large panel of molecules with relevant applicative properties and industrial reality (Scheme 2).12 Isosorbide dinitrate is used since several decades as vasodilator.13, 14 The dimethyl isosorbide is for example used as solvent in cosmetics15-17 and isosorbide diesters18-22 are actually industrially produced and commercialized as surfactants23-27 and PVC plasticizer28, 29 . The rigid scaffold associated to the bifunctionality of the molecule has attracted a strong interest in the field of polymers chemistry. Isosorbide and derivatives have thus been shown as suitable monomers for the industrial production of polycarbonates30, 31, polyesters32-41 or polyamides42-44, with attractive applicative properties. For example, isosorbide allows the increase of Tg, improves the scratch resistance and gives excellent optical properties to polymers. Polyesters and polycarbonates containing isosorbide have now commercial developments in food packaging, spray container, automotive, material for electronic devices … .

Conclusions

Isosorbide is a versatile platform molecule that shows key features to make it a credible alternative to petro-based products. The molecule is already available on large industrial scale (tens of thousands tons per years), which allows its development in commercial products such as active pharma ingredient, additive for cosmetic, speciality chemicals and polymers (ex: polycarbonates – polyesters). The development of more selective and higher yields syntheses of isosorbide are greatly needed to consolidate isosorbide production in view of a large expansion of its uses. Sorbitol conversion to isosorbide, relying on a starch route, is already a tough challenge. In a farther future, development of a credible path to isosorbide relying on cellulose source could even be thought of, provided that very versatile innovative catalysts will be developed in the next years. In all cases, a key issue is to develop catalysts that will avoid the massive production of “oligomeric/polymeric” by-products in order to access more sustainable processes by limiting the amounts of wastes produced during the synthesis. For this purpose, more selective homogeneous catalysts than the conventional Brønsted acids or alternative reaction conditions would be of strong interest. Selective and recyclable heterogeneous catalysts would be even more profitable as they would allow the continuous production of catalyst free isosorbide. This latter approach faces strong limitations due to the need of high reaction temperatures that often result in high amounts of side-products and the need of frequent and often tedious catalyst regeneration. Innovation concerning isosorbide synthesis is still an open field on which the design of efficient and robust catalysts, either homogeneous or heterogeneous, is a key issue. Such developments would pave the way to high scale effective processes considering altogether synthesis and purification of isosorbide.

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Image result for ISOSORBIDE SYNTHESIS

Isosorbide is a heterocyclic compound that is derived from glucose. Isosorbide and its two isomers, namely isoidide and isomannide, are 1,4:3,6-dianhydrohexitols. It is a white solid that is prepared from the double dehydration of sorbitol. Isosorbide is a non-toxic diolproduced from biobased feedstocks, that is biodegradable and thermally stable. It is used in medicine and has been touted as a potential biofeedstock.

Production

Hydrogenation of glucose gives sorbitol. Isosorbide is obtained by double dehydration of sorbitol:

(CHOH)₄(CH₂OH)₂ → C₆H₁₀O₂(OH)₂ + 2 H₂O

An intermediate in the dehydration is the monocycle sorbitan.^[1]

Application

Isosorbide is used as a diuretic, mainly to treat hydrocephalus, and is also used to treat glaucoma.^[2] Other medications are derived from isosorbide, including isosorbide dinitrate and isosorbide mononitrate, are used to treat angina pectoris. Other isosorbide-based medicines are used as osmotic diuretics and for treatment of esophageal varices. Like other nitric oxide donors (see biological functions of nitric oxide), these drugs lower portal pressure by vasodilation and decreasing cardiac output. Isosorbide dinitrate and hydralazineare the two components of the anti-hypertensive drug isosorbide dinitrate/hydralazine (Bidil).

Isosorbide is also used as a building block for bio based polymers such as polyesters.^[3]

References

Jump up^ M. Rose, R. Palkovits (2012). “Isosorbide as a Renewable Platform chemical for Versatile Applications—Quo Vadis?”. ChemSusChem. 5 (1): 167–176. PMID 22213713. doi:10.1002/cssc.201100580.
Jump up^ CID 12597 from PubChem
Jump up^ Bersot J.C. (2011). “Efficiency Increase of Poly (ethylene terephthalate‐co‐isosorbide terephthalate) Synthesis using Bimetallic Catalytic Systems”. Macromol. Chem. Phys. 212 (19): 2114–2120. doi:10.1002/macp.201100146.

Isosorbide
Names

Other names D-Isosorbide; 1,4:3,6-Dianhydro-D-sorbitol; 1,4-Dianhydrosorbitol
Identifiers
CAS Number	652-67-5
3D model (JSmol)	Interactive image
ChemSpider	12077
ECHA InfoCard	100.010.449
KEGG	D00347
PubChem CID	12597
UNII	WXR179L51S
InChI [show]
SMILES [show]
Properties
Chemical formula	C₆H₁₀O₄
Molar mass	146.14 g·mol⁻¹
Appearance	Highly hygroscopic white flakes
Density	1.30 at 25 °C
Melting point	62.5 to 63 °C (144.5 to 145.4 °F; 335.6 to 336.1 K)
Boiling point	160 °C (320 °F; 433 K) at 10 mmHg
Solubility in water	in water (>850 g/L), alcoholsand ketones
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

From the net

Image result for ISOSORBIDE SYNTHESIS

1H Nuclear magnetic resonance (NMR) spectra of PTMG, isosorbide, HDI, and polyurethane.HDI: hexamethylene diisocyanate; PTMG: poly(tetramethylene glycol).

Image result for ISOSORBIDE SYNTHESIS

REF

http://www.rsc.org/suppdata/gc/c4/c4gc01822b/c4gc01822b1.pdf

Synthesis of five- and six-membered heterocycles by dimethyl carbonate with catalytic amount of nitrogen bicyclic bases

http://pubs.rsc.org/en/content/articlelanding/2015/gc/c4gc01822b#!divAbstract

F. Aricò, a,*S. Evaristoa and P. Tundoa,*

Catalytic amount of a nitrogen bicyclic base, i.e., DABCO, DBU and TBD is effective for the one-pot synthesis of heterocycles from 1,4-, 1,5-diols and 1,4-bifunctional compounds via dimethyl carbonate chemistry under neat conditions. Nitrogen bicyclic bases, that previously showed to enhance the reactivity of DMC in methoxycarbonylation reaction by BAc2 mechanism, are herein used for the first time as efficient catalysts for cyclization reaction encompassing both BAc2 and BAl2 pathways. This synthetic procedure was also applied to a large scale synthesis of cyclic sugars isosorbide and isomannide starting from D-sorbitol and D-mannitol, respectively. The resulting anhydro sugar alcohols were obtained as pure crystalline compounds that did not require any further purification or crystallization.

Image result for ISOSORBIDE SYNTHESIS

Larger scale synthesis of isosorbide: In a round bottom flask equipped with a reflux condenser, D-sorbitol (0.05 mol, 1.00 mol. eq.), DMC (0.44 mol, 8.00 mol. eq.), DBU (2.70 mmol, 0.05 mol. eq.) and MeOH (20.00 mL) were heated at reflux while stirring. The progress of the reaction was monitored by NMR. After 48 hours the reaction was stopped, cooled at room temperature and the mixture was filtered over Gooch n°4. Finally, DMC was evaporated under vacuum and the product was obtained as pure in 98% yield (7.90 g, 0.05 mol). Characterization data were consistent with those obtained for the commercially available compound.