N-Butylpyrrolidinone as a dipolar aprotic solvent for organic synthesis

N-Butylpyrrolidinone as a dipolar aprotic solvent for organic synthesis

Green Chem., 2016, 18,3990-3996
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., 2016,18, 3990-3996

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.

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

Mechanisms and reactivity differences of proline-mediated catalysis in water and organic solvents

Catal. Sci. Technol., 2016, 6,3378-3385
DOI: 10.1039/C6CY00033A, Paper
Gang Yang, Lijun Zhou
Several key issues regarding the mechanisms of proline catalysis are unravelled by first-principles calculations that can guide future catalyst design.

Mechanisms and reactivity differences of proline-mediated catalysis in water and organic solvents

Gang Yang*a and   Lijun Zhoua  
*Corresponding authors
aCollege of Resource and Environment & Chongqing Key Laboratory of Soil Multi-scale Interfacial Process, Southwest University, Chongqing, PR China
E-mail: theobiochem@gmail.com
Fax: +86 023 68250444
Tel: +86 023 68251545
Catal. Sci. Technol., 2016,6, 3378-3385

DOI: 10.1039/C6CY00033A

Proline is an efficient and versatile catalyst for organic reactions while a number of issues remain controversial. Here, ab initio and density functional calculations were used to unravel a few key issues of catalytic mechanisms in water and organic solvents. Zwitterionic proline that predominates in water and DMSO is assumed to be the active conformation for catalysis, and reactivity differences in two solvents are revealed. Meanwhile, an abundance of experimental observations can be finely interpreted by the present computational results, including those seemingly contradictory. Although bearing lower activation barriers than that in DMSO, the production of enamines and further aldol products in water will be blocked at an early stage (J. Am. Chem. Soc., 2006, 128, 734) because the reaction in water is significantly driven towards acetyl formation that is kinetically and thermodynamically preferred. Due to significant promotion of the rate-determining proton transfer step, aldol reactions in organic solvents can be obviously initiated by the addition of some water (Angew. Chem., Int. Ed., 2004, 43, 1983). In order to show catalytic effects in water (an obviously environmentally benign solvent), proline has to be structurally modified so that canonical structures can be the principal (or sole) conformations, which is in line with the analyses of all proline-based catalysts available in water (e.g., J. Am. Chem. Soc., 2006, 128, 734, Catal. Commun., 2012, 26, 6). Thus, the present results provide insightful clues to mechanisms of proline-mediated catalysis as well as future design of more efficient catalysts.
//////Mechanisms,  reactivity,  differences,  proline-mediated catalysis, water ,  organic solvents

Intensified biocatalytic production of enantiomerically pure halophenylalanines from acrylic acids using ammonium carbamate as the ammonia source

Catal. Sci. Technol., 2016, Advance Article
DOI: 10.1039/C6CY00855K, Communication
Nicholas J. Weise, Syed T. Ahmed, Fabio Parmeggiani, Elina Siirola, Ahir Pushpanath, Ursula Schell, Nicholas J. Turner
An industrial-scale method employing a phenylalanine ammonia lyase enzyme

Intensified biocatalytic production of enantiomerically pure halophenylalanines from acrylic acids using ammonium carbamate as the ammonia source

*Corresponding authors
aManchester Institute of Biotechnology & School of Chemistry, University of Manchester, 131 Princess Street, Manchester, UK
E-mail: nicholas.turner@manchester.ac.uk
bJohnson Matthey Catalysts and Chiral Technologies, 28 Cambridge Science Park, Milton Road, Cambridge, UK
Catal. Sci. Technol., 2016, Advance Article

DOI: 10.1039/C6CY00855K


An intensified, industrially-relevant strategy for the production of enantiopure halophenylalanines has been developed using the novel combination of a cyanobacterial phenylalanine ammonia lyase (PAL) and ammonium carbamate reaction buffer. The process boasts STYs up to >200 g L−1 d−1, ees ≥ 98% and simplified catalyst/reaction buffer preparation and work up.





///////Intensified,  biocatalytic production, enantiomerically pure,  halophenylalanines,  acrylic acids,  ammonium carbamate, ammonia source


Green Chem., 2016, Advance Article

DOI: 10.1039/C5GC02977E, Communication

Ryosuke Matake, Yusuke Adachi, Hiroshi Matsubara

A convenient preparation of vinyl ethers from alcohols with calcium carbide was developed. This protocol is an alternative to the Favorskii-Reppe reaction without any high pressure device.

Vinyl ethers are important and useful synthetic building blocks. Using a test tube with a screw cap, a convenient preparation of vinyl ethers from alcohols with calcium carbide under superbasic catalytic conditions (KOH/DMSO) was developed. The vinylation of primary and secondary alcohols was successfully achieved, affording the desired products in good yields. The gram-scale preparation of a vinyl ether was also demonstrated. In this reaction, calcium carbide acts as an acetylene source, constituting a safer alternative to acetylene gas.

 F. de Nanteuil, E. Serrano, D. Perrotta and J. Waser, J. Am. Chem. Soc., 2014, 136, 6239.


1H NMR PREDICT using nmrdb , signals may vary , use your discretion to understand sequence



Synthesis of vinyl ethers of alcohols using calcium carbide under superbasic catalytic conditions (KOH/DMSO)

*Corresponding authors

aDepartment of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Japan

Green Chem., 2016, Advance Article

DOI: 10.1039/C5GC02977E


Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Scheme 1

Control experiments.

The ubiquitous oxazoles have attracted more and more attention in both industrial and academic fields for decades. This interest arises from the fact that a variety of natural and synthetic compounds which contain the oxazole substructure exhibit significant biological activities and antiviral properties. Although various synthetic methodologies for synthesis of oxazols have been reported, the development of milder and more general procedure to access oxazoles is still desirable.

Initially, compound A, formed by the substitution reaction of 1a with 2a, which can be transformed following two pathways: (a) I+, generated by the oxidation of iodine, could oxidize A to radical intermediate B, which eliminates one molecular of CO2 to generate radical C, which is further oxidized to imine Dor its isomer E. Subsequently, F is obtained by intramolecular nucleophilic addition of E. Finally, the desired product (3a) is given by deprotonation and oxidation of F; (b) G is formed from the oxidation of A. Then 3a is obtained through H, I, J, K following a process similar to path a.

Scheme 2

Plausible mechanism.

General procedure for the synthesis of polysubstituted oxazoles

1a (105.8 mg, 0.7 mmol), 2a (99.5 mg, 0.5 mmol), I2 (50.8 mg, 0.2 mmol), DMA (2 mL) and TBHP (70% aqueous solution, 1 mmol) were placed in a tube (10 mL) and sealed with a thin film. Then the reaction mixture was stirred at 25°C for 4 h, heated up to 60°C and stirred at this temperature for another 4 h. After that, the resulting mixture was cooled to the room temperature, diluted with water, extracted with ethyl acetate. The organic phase was washed with saturation sodium chloride solution, dried and filtrated. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column separation (petroleum ether:ethyl acetate = 10:1) to give 3a(154.7 mg, 70%) as light yellow solid, mp = 70–72°C.

2,5-diphenyloxazole (3a) [1]

Synthesized according to typical procedure and purified by column chromatography (petroleum ether:ethyl acetate = 10:1) to give light yellow solid (154.7 mg, 70%), mp = 70-72 °C.

1H NMR (300 MHz, CDCl3): δ 8.12-8.09 (m, 2 H), 7.72-7.69 (m, 2 H), 7.50-7.40 (m, 6 H), 7.35-7.24 (m, 1 H).

13C NMR (75 MHz, CDCl3): δ 161.3, 151.4, 130.4, 129.0, 128.9, 128.5, 128.1, 127.6, 126.4, 124.3, 123.6.

HRMS (APCI-FTMS) m/z: [M + H]+ calcd for C15H12NO: 222.0913, Found: 222.0911.

D1 D2

The scope of the reaction. Standard conditions: 0.7 mmol of amino acids (1a1h), 0.5 mmol of2a2j, 0.1 mmol of I2, 1 mmol of TBHP, 2 mL of DMA, were stirred at 25°C for 4 h then slowly raised to 60°C for 4 h. Catalysts amount and isolated yields were based on 2.

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Yunfeng Li, Fengfeng Guo, Zhenggen Zha and Zhiyong Wang*

Zhiyong Wang

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

Sustainable Chemical Processes 2013, 1:8  doi:10.1186/2043-7129-1-8

The electronic version of this article is the complete one and can be found online at:http://www.sustainablechemicalprocesses.com/content/1/1/8


WANG Zhiyong(汪志勇)

Ph.D., University of Science and Technology of China (USTC) (1992); M.S., USTC (1989); B.S., Anhui Normal University (1982).

Professor of Chemistry
Department of Chemistry
School of Chemistry and Materials Science
University of Science and Technology of China
Hefei, Anhui 230026, P. R. China

Tel: 86-551-63603185
Fax: 86-551-63603185
E-mail: zwang3@ustc.edu.cn
Personal Homepage:

    Research in our group will focus on the general areas of reaction development and chemical synthesis. Our studies will be driven by the discovery of new and useful catalysts. By virtue of the developed organic reactions various organic ligands are synthesized and used as probes in biological progress. Brief summaries of three research directions illustrating these objectives are shown below:
    1) The preparation of heterogeneous catalysts;
    2) The theoretical calculation for the mechanism of organic reactions;
    The application of organic ligands as probes or inhibitors to explore the molecular mechanism of HIV transcription.


    WANG Zhiyong, Professor
    Name: Zhiyong Wang(汪志勇)
    Born: June, 1962, Anhui, P. R. China
    Address: Department of Chemistry, University of Science and Technology of China, 230026 Hefei, P. R. China
    Tel: 86-551-63603185
    Fax: 86-551-63603185
    E-mail: zwang3@ustc.edu.cn
     1978-1982 B.S., Anhui Normal University
     1982-1986 Lecturer, South Anhui Agricultural College, China
     1986-1989 M.S., University of Science and Technology of China
     1989-1992 Ph.D., University of Science and Technology of China
     1992-1997 Lecturer, Associate Professor, University of Science and Technology of China
     1997-1999 Research Fellow, Tulane University & Brandeis University
     1999-Now Professor of Chemistry, University of Science and Technology of China
    1) Organic reactions in aqueous media and development of synthetic methodology;
    2) Supramolecular assembly under the control of organic ligands;
    3) Drug design on the base of PCAF bromodomain.
    1) Organic reactions in water mediated by nano-metals and its application in asymmetric synthesis, National Natural Science Foundation (2004-2006)
    2) Crystal Engineering under control of organic ligands, Foundation from Education Department of Anhui Province (2003-2005)
    1) C-F. Pan, M. Meze, S. Mujtaba, M. Muller, L. Zeng, J-M. Li, Z-Y. Wang,* M-M. Zhou*
    “Structure-Guided Optimization of Small Molecules Selectively Inhibiting HIV-1 Tat and PCAF Association” J. Med. Chem., 2007, 50, 2285
    2) Y. Xie, Z-P. Yu, X-Y. Huang, Z-Y. Wang,* L-W. Niu, M-K. Teng, J. Li
    “Rational Design on the MOFs Constructed from modified Aromatic Amino Acids”
    Chem. Eur. J., 2007, 13, 9399
    3) Z-H. Zhang, C-F. Pan, Z-Y. Wang* “Synthesis of chromanones: a novel palladium-catalyzed Wacker-type oxidative cyclization involving 1,5-hydride alkyl to palladium migration” Chem. Commun, 2007, 4686
    4) Y. Xie, Y. Yan, H-H. Wu, G-P. Yong, Y. Cui, Z-Y. Wang*, L. Pan, J. Li “Homochiral Metal-organic Coordination Networks from L-Tryptophan” Inorg. Chim. Acta., 2007, 360,1669
    5) Y. Xie, H-H. Wu, G-P. Yong,, Z-Y. Wang*, R. Fan , R-P. Li, G-Q. Pan, Y-C. Tian, L-S. Sheng, L. Pan, J. Li “Synthesis, Crystal Structure, Spectroscopic and Magnetic Properties of Two Cobalt Molecules Constructed from Histidine” J. Mol. Struct., 2007, 833, 88
    6) Z-H. Zhang, Z-Y. Wang* “Diatomite-Supported Pd Nanoparticles: An Efficient Catalyst for Heck and Suzuki Reactions” J. Org. Chem., 2006, 71, 7485
    7) Z-H. Zhang, Z-G. Zha, C-S. Gan, C-F. Pan, Y-Q. Zhou, Z-Y. Wang*, M-M. Zhou* “Catalysis and Regioselectivity of the Aqueous Heck Reaction by Pd(0) Nanoparticles under Ultrasonic Irradiation”
    J. Org. Chem., 2006, 71, 4339

Hefei, Anhui China

////Metal-free,  Synthesis,  Oxazoles, Oxidation,  Decarboxylative cyclization,  α-amino acids

8-Oxo-5-aza-spiro[2.5]octane-5-carboxylic acid benzyl ester,





8-Oxo-5-aza-spiro[2.5]octane-5,7-dicarboxylic acid 5 benzyl ester 7 methyl ester



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