CO2-Catalysed aldol condensation of 5-hydroxymethylfurfural and acetone to a jet fuel precursor

CO2-Catalysed aldol condensation of 5-hydroxymethylfurfural and acetone to a jet fuel precursor

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC01697A, Communication
Roland Lee, Jesse R. Vanderveen, Pascale Champagne, Philip G. Jessop
CO2 can act as a catalyst for the production of bio-jet fuel precursors through aldol condensation.

CO2-Catalysed aldol condensation of 5-hydroxymethylfurfural and acetone to a jet fuel precursor

 *Corresponding authors
aDepartment of Chemistry, Queen’s University, Kingston, Canada K7L 3N6
E-mail: Philip.jessop@queensu.ca
bDepartment of Civil Engineering, Queen’s University, Kingston, Canada K7L 3N6
Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC01697A, http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC01697A?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

CO2 can act as a catalyst for the production of bio-jet fuel precursors through aldol condensation. CO2-Catalysed aldol condensation of HMF with acetone gives a >95% yield of [4-(5-hydroxymethyl-2-furyl)-3-butenone] mono-aldol condensate, while direct conversion of glucose to the same mono-aldol condensate gave a yield of 11%
Method Single step dehydration, aldol condensation, and hydrogenation was carried out in a Parr 31 mL high pressure vessel (T316SS, Parr no. N4742, modified to 31 mL). Glucose/5-HMF, hydrogenation catalyst (Pt (nominally 50 %), Ru (nominally 25 %) on high surface area advanced carbon support supplied by Alfa Aesar (stock# 12100) and reaction solvents were added to the Parr vessel equipped with a stir bar. The vessel was then closed and heated in an oil bath to the required temperature and allowed to equilibrate for 30 min. Following equilibration, the reactor was pressurized with CO2 and H2 to operating conditions. Following reaction (both for conversion of 5-HMF to aldol condensation product or direct conversion from glucose) and dilution, the samples were analyzed with the use of GC-MS (Perkin Elmer Clarus 680 gas chromatograph (GC)), using an Elite-5MS column (30 m, 250 µm i.d., 0.25 µm film of 5% diphenyl 95% dimethyl polysiloxane). Initially the temperature was held at 30 °C for 0 min, followed by a ramp to 125 °C at a rate of 2.5 °C /min held for 1 min, ramp to 260 °C at a rate of 20 °C /min held for 1 min and, finally, ramp to 300 °C at a rate of 20 °C /min held for 3 min. The injector temperature was held at 250 °C and the detector at 200 °C for the duration of the analysis. Carrier gas (helium) flow rate was maintained at 1 mL/min. Aldol condensation products were independently prepared by a literature method17 and utilized for calibration and determination of retention time. Chromatograms and data were collected precisely with the use of Perkin Elmer TurboMass, version 5.4.2.1617 chromatography software.
Image result for bio-jet fuel precursors
Scheme 1 Proposed conversion of cellulose to biomass derived jet fuel.
Image result for bio-jet fuel precursors
Image result for bio-jet fuel precursors
///////////CO2-Catalysed,  aldol condensation, -hydroxymethylfurfural, jet fuel precursor

Visible-light induced oxidative Csp3-H activation of methyl aromatics to methyl esters

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC01880G, Communication
Lingling Zhang, Hong Yi, Jue Wang, Aiwen Lei
A mild and catalytic oxidative Csp3-H activation of methyl aromatics using O2via photocatalysis has been achieved. A lot of methyl aromatics can be tolerated, providing a route for aromatic methyl carboxylates. In addition, this protocol can be performed on a gram scale
Visible-light induced oxidative Csp3-H activation of methyl aromatics to methyl esters

Visible-light induced oxidative Csp3–H activation of methyl aromatics to methyl esters

Lingling Zhang,a   Hong Yi,a   Jue Wanga and   Aiwen Lei*ab  
*Corresponding authors
aCollege of Chemistry and Molecular Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan, P. R. China
E-mail: aiwenlei@whu.edu.cn
bNational Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, P. R. China
Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC01880G. http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC01880G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Direct functionalization of readily available hydrocarbons under mild conditions fulfills the requirements of green and sustainable chemistry. In this work, a mild and green catalytic oxidative Csp3–H activation of methyl aromatics using O2 via photocatalysis has been achieved. A lot of methyl aromatics can be tolerated, providing a green route for aromatic methyl carboxylates. In addition, this protocol can be performed on a gram scale.
str1 str2
Methyl 4-methylbenzoate (2a): [1] 32.9 mg (yield: 73%, light yellow oil). 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.1 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 3.73 (s, 3H), 2.22 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.0, 143.5, 129.6, 129.0, 127.4, 51.8, 21.5.
Liu, H.; Chen, G.; Jiang, H.; Li, Y.; Luque, R., ChemSusChem. 2012, 5 , 1892-1896.
///////Visible-light,  induced oxidative,  Csp3-H activation,  methyl aromatics, methyl esters

High Throughput Enzymatic Enantiomeric Excess: Quick-ee

.

High throughput screening techniques (HTS) are fast and efficient alternatives to evaluate enzymatic activities. Here, this technique is applied to obtain enantiomeric excess and conversions values with chiral fluorogenic probes and a non fluorogenic competitor, which was named Quick-ee. The fluorescent signal reveals of the enantioselectivity of the enzyme. Details are presented in the Article High Throughput Enzymatic Enantiomeric Excess: Quick-ee by Maria L. S. de O. Lima, Caroline C. da S. Gonçalves, Juliana C. Barreiro, Quezia Bezerra Cass and Anita Jocelyne Marsaioli on page 319.

http://dx.doi.org/10.5935/0103-5053.20140282

Cover Article

J. Braz. Chem. Soc. 2015, 26(2), 319-324

High Throughput Enzymatic Enantiomeric Excess: Quick-ee

Maria L. S. O. Lima; Caroline C. S. Gonçalves; Juliana C. Barreiro; Quezia B. Cass; Anita J. Marsaioli

Lima MLSO, Gonçalves CCS, Barreiro JC, Cass QB, Marsaioli AJ. High Throughput Enzymatic Enantiomeric Excess: Quick-ee.J. Braz. Chem. Soc. 2015;26(2):319-324

/////////////High Throughput,  Enzymatic,  Enantiomeric Excess,  Quick-ee

http://jbcs.sbq.org.br/imagebank/pdf/v26n2a14.pdf

http://jbcs.sbq.org.br/imagebank/pdf/v26n2a14-Sup01.pdf

Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material

str1

Abstract Image

Efficient continuous Grignard and lithiation processes were developed to produce one of the key regulatory starting materials for the production of edivoxetine hydrochoride. For the Grignard process, organometallic reagent formation, Bouveault formylation, reduction, and workup steps were run in continuous stirred tank reactors (CSTRs). The lithiation utilized a hybrid approach where plug flow reactors (PFRs) were used for the metal halogen exchange and Bouveault formylation steps, while the reduction and workup steps were performed in CSTRs. Relative to traditional batch processing, both approaches offer significant advantages. Both processes were high-yielding and produced the product in high purity. The two main processes were directly compared from a number of perspectives including reagent and operational safety, fouling potential, process footprint, need for manual operation, and product yield and purity.

Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material

Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, United States
D&M Continuous Solutions, LLC, Greenwood, Indiana 46143, United States
Org. Process Res. Dev., Article ASAP

//////////Flow Grignard,  Lithiation, Screening Tools,  Development, Continuous Processes,  Benzyl Alcohol, Starting Material

Day 10 of the 2016 Doodle Fruit Games! Find out more at g.co/fruit

The continuous flow Barbier reaction: an improved environmental alternative to the Grignard reaction?

A key pharmaceutical intermediate (1) for production of edivoxetine·HCl was prepared in >99% ee via a continuous Barbier reaction, which improves the greenness of the process relative to a traditional Grignard batch process. The Barbier flow process was run optimally by Eli Lilly and Company in a series of continuous stirred tank reactors (CSTR) where residence times, solventcomposition, stoichiometry, and operations temperature were optimized to produce 12 g h−1crude ketone 6 with 98% ee and 88% in situ yield for 47 hours total flow time. Continuous salt formation and isolation of intermediate 1 from the ketone solution was demonstrated at 89% yield, >99% purity, and 22 g h−1 production rates using MSMPRs in series for 18 hours total flow time. Key benefits to this continuous approach include greater than 30% reduced process mass intensity and magnesium usage relative to a traditional batch process. In addition, the flow process imparts significant process safety benefits for Barbier/Grignard processes including >100× less excess magnesium to quench, >100× less diisobutylaluminum hydride to initiate, and in this system, maximum long-term scale is expected to be 50 L which replaces 4000–6000 L batch reactors.

A continuous flow Barbier reaction was employed for the production of a key pharmaceutical intermediate (1) in the synthesis of edivoxetine·HCl (a highly selective norepinephrine re-uptake inhibitor).

US scientists from Eli Lilly and Company and D&M Continuous Solutions, led by Michael Kopach, report the development of a continuous Barbier reaction which preserves chirality and the product obtained in >99% ee.  The team ran the process in a series of continuous stirred tank reactors, where residence time, solvent composition, stoichiometry and operations temperature were optimised to produce 12 g per hour of the ketone precursor to 1 with 98% ee and 88% in situ yield for 47 hours total flow time.  Continuous salt formation and isolation of 1 could then be achieved from the ketone solution with >99% purity.

This process offers up several significant advantages over a traditional Grignard batch process.  This continuous flow method gave greater than 30% reduced process mass intensity and magnesium usage relative to the batch method.  Equally, the flow process resulted in >100 x less excess magnesium to quench and >100 x less diisobutylaluminum hydride to initiate giving significant safety benefits.  The authors expect that the maximum long-term scale of the process is 50 L which would replace 4000-6000 L batch reactors.

Continuous Flow Barbier Reaction

Figure 2. Continuous Barbier Laboratory Setup

For 100 years, Grignard reactions have been one of the most powerful and effi cient organic chemistry methodologies for C-C bond formation. However, Grignard reactions are also among the most challenging reactions from both operational and potential safety issues due to initiation diffi culties and runaway potential. A close variation to the Grignard reaction is the Barbier reaction wherein the Grignard reagent is prepared in the presence of an electrophile resulting in the immediate consumption of the Grignard. A Barbier reaction using a CSTR was developed for a key pharmaceutical intermediate in production of edivoxetine·HCl (Scheme 4) [9]. In the fl ow setup (Figure 2), solid magnesium is sequestered in the fi rst tank where the Grignard initiation event takes place. CSTR 2 was used as an aging tank and CSTR 3 was the quench tank. CSTRs were used for Grignard reaction rather than a PFDR because of the solid Mg reagent.

Scheme 4: Barbier Reaction to form Ketone 15

Continuous reaction improved process safety, product quality, and process greenness. The continuous reaction achieved >99% ee in situ versus 95% ee batch because of immediate conversion of unstable intermediate. Solvent volumes were reduced 30%. The safety hazards were reduced by decreasing the reactor size by 50X, which reduced chemical potential and also increased heat transfer surface area per unit volume by 4X. DIBAL-H initiating agent was reduced by more than 100X, and excess Mg that must be quenched at the end of reaction was almost eliminated. When run continuously, the commercial scale Grignard formation reactor was expected to be 50L, which replaces 4000-6000L batch reactor.

The continuous flow Barbier reaction: an improved environmental alternative to the Grignard reaction?

*Corresponding authors
aChemical Product Research and Development, Eli Lilly and Company, Indianapolis, USA
E-mail: kopach_michael@lilly.com
bD&M Continuous Solutions, Indianapolis, USA
Green Chem., 2012,14, 1524-1536

DOI: 10.1039/C2GC35050E

http://pubs.rsc.org/en/Content/ArticleLanding/2012/GC/C2GC35050E#!divAbstract

Three vessel Grignard CSTR process train.

Grignard synthesis of compound 1.

Retrosynthesis of edivoxetine·HCl.

Flow diagram for the whole continuous process from amide 3 to product 1.

Continuous crystallization of compound 1.

Distillation and continuous crystallization of compound 1.

Entry, Rxn temp. (°C), Vol. ratio THF–toluene (%), Conversion (%), ee (%)

//////////The continuous flow,  Barbier reaction,  improved environmental alternative,  Grignard reaction, FLOW SYNTHESIS

Day 10 of the 2016 Doodle Fruit Games! Find out more at g.co/fruit

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

*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

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.

 

str1

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

Aqua Mediated One-Pot Synthesis of 2-Amino-tetrahydrobenzo[b]pyran Derivatives Catalyzed by Mg(NO3)2•6H2O

.

http://benthamscience.com/journal/abstracts.php?journalID=loc&articleID=121326

Aqua Mediated One-Pot Synthesis of 2-Amino-tetrahydrobenzo[b]pyran Derivatives Catalyzed by Mg(NO3)2•6H2O

Letters in Organic Chemistry

Volume: 11
Issue Number: 7
First Page: 475
Last Page: 479
Page Count: 5
DOI: 10.2174/1570178611666140401221534

Author(s): Boudjemaa Boumoud, Amina Debbache, Taoues Boumoud, Raouf Boulcina and Abdelmadjid Debache

Affiliation: Laboratoire de Synthese de Molecules d’ Interets Biologiques, Departement de Chimie, Faculte des Sciences Exactes, Universite Constantine 1, 25000 Constantine, Algerie.
Abstract

We describe herein a clean and efficient one-pot synthesis of 4H-benzo[b]pyran derivatives using dimedone, active methylene nitriles and aryl aldehyde via Knoevenagel condensation followed by Michael addition in the presence of Mg(NO3)2•6H2O as catalyst and water as a green solvent. The advantages of this method lie in its simplicity, low catalyst loading, cost effectiveness and easy handling. The present method also allows us to synthesize highly functionalized tetrahydrobenzo[b]pyran derivatives from simple and readily available starting materials.

 

 

 

 

 

 

 

 

///