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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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

Continuous Synthesis of Organozinc Halides Coupled to Negishi Reactions

Continuous Synthesis of Organozinc Halides Coupled to Negishi Reactions  Article first published online: 20 JUN 2014 DOI: 10.1002/adsc.201400243   Advanced Synthesis & Catalysis Volume 356, Issue 18, pages 3737–3741, December 15, 2014

Nerea Alonso2,3, L. Zane Miller1, Juan de M. Muñoz2, Jesus Alcázar2,* D. Tyler McQuade1,*

1Department of Chemistry and Biochemistry, Florida State University, USA 2Janssen Research and Development, Janssen-Cilag, Toledo, Spain 3Facultad de Química, Universidad de Castilla-La Mancha, Spain   The Negishi cross-coupling is a powerful CC bond forming reaction. The method is less commonly used relative to other cross-coupling methods in part due to lack of availability of organozinc species. While organozinc species can be prepared, problems with reproducibility and handling of these sensitive species can complicate these reactions. Herein, we describe the continuous formation, using an activated packed-bed of metallic zinc, and subsequent use of organozinc halides. We demonstrate that a single column of zinc can provide excellent yields of organozinc halides and that they can be used downstream in subsequent Negishi cross-couplings. The preparation of the zinc column and the scope of the reaction are discussed.

Click here to go straight to the publication http://onlinelibrary.wiley.com/doi/10.1002/adsc.201400243/abstract