Improving the efficiency of the Diels-Alder process by using flow chemistry and zeolite catalysis

• Improving the efficiency of the Diels-Alder process by using flow chemistry and zeolite catalysis
• Green Chem., 2017, Advance Article
  DOI: 10.1039/C6GC02334G, Paper

  S. Seghers, L. Protasova, S. Mullens, J. W. Thybaut, C. V. Stevens
  The industrial application of the Diels-Alder reaction for the synthesis of (hetero)cyclic compounds constitutes an important challenge. To tackle the reagent instability problems and corresponding safety issues, the use of a high-pressure and zeolite catalysed microreactor process is presented.

The industrial application of the Diels–Alder reaction for the atom-efficient synthesis of (hetero)cyclic compounds constitutes an important challenge. Safety and purity concerns, related to the instability of the polymerization prone diene and/or dienophile, limit the scalability of the production capacity of Diels–Alder products in a batch mode. To tackle these problems, the use of a high-pressure continuous microreactor process was considered. In order to increase the yields and the selectivity towards the endo-isomer, commercially available zeolites were used as a heterogeneous catalyst in a microscale packed bed reactor. As a result, a high conversion (≥95%) and endo-selectivity (89:11) were reached for the reaction of cyclopentadiene and methyl acrylate, using a 1:1 stoichiometry. A throughput of 0.87 g h⁻¹during at least 7 h was reached, corresponding to a 3.5 times higher catalytic productivity and a 14 times higher production of Diels–Alder adducts in comparison to the heterogeneous lab-scale batch process. Catalyst deactivation was hardly observed within this time frame. Moreover, complete regeneration of the zeolite was demonstrated using a straightforward calcination procedure

Improving the efficiency of the Diels–Alder process by using flow chemistry and zeolite catalysis

S. Seghers,^a   L. Protasova,^b   S. Mullens,^b  J. W. Thybaut^c and   C. V. Stevens*^a  

*

Corresponding authors

^a

SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
E-mail: chris.stevens@ugent.be

^b

VITO, Vlaamse Instelling voor Technologisch Onderzoek, Boeretang 200, 2400 Mol, Belgium

^c

Laboratory for Chemical Technology, Department of Chemical Engineering and Technical Chemistry, Faculty of Engineering and Architecture, Ghent University, Technologiepark 914, 9052 Ghent, Belgium

Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC02334G
http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC02334G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

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Scheme 1. Diene-Transmissive Diels–Alder Cycloaddition Sequences of [3]- and [4]Dendralene with the Prototypical Olefinic Dienophile

The first synthesis of all five possible monomethylated [4]dendralenes has been achieved via two distinct synthetic strategies. The Diels–Alder chemistry of these new dendralenes (as multidienes) with an electron poor dienophile, N-methylmaleimide (NMM), has been studied. Thus, simply upon mixing the dendralene and an excess of dienophile at ambient temperature in a common solvent, sequences of cycloadditions result in the rapid generation of complex multicyclic products. Distinct product distributions are obtained with differently substituted dendralenes, demonstrating that dendralene substitution influences the pathway followed, when a matrix of mechanistic possibilities exists. Dendralene site selectivities are traced to electronic, steric and conformational effects, thereby allowing predictive tools for applications of substituted dendralenes in future synthetic endeavors.

Scheme 2. Diene-Transmissive Diels–Alder Cycloaddition Sequences of [4]Dendralene (1) with the Dienophile N-Methylmaleimide (NMM)

Scheme 3. Syntheses of the Five Mono-Methyl-Substituted-[4]Dendralenes

3 Diels-Alder reactions in 1 go

 
FROM https://naturalproductman.wordpress.com/2016/01/29/11137/

Tris-adduct 36

An analytic sample of 36 was obtained by recrystallization from EtOAc/hexane to give colorless needles, mp 255–257 °C; R_f 0.20 (EtOAc, 100%);  

¹H NMR (300 MHz, CDCl₃) δ 3.22 (dd, J = 8.6, 5.9 Hz, 1H), 3.19–3.07 (m, 3H), 3.04–2.91 (m, 5H), 2.90 (s, 6H), 2.86 (s, 3H), 2.65 (ddd, J = 14.1, 13.4, 5.4 Hz, 1H), 2.35 (ddd, J = 14.3, 5.0, 2.5 Hz, 1H), 2.16–2.05 (m, 2H), 2.03–1.91 (m, 1H), 1.85–1.74 (m, 1H), 1.54 (d, J = 6.8 Hz, 3H) ppm;  

¹³C NMR (75 MHz, CDCl₃) δ 179.7 (C), 178.5 (C), 178.4 (C), 178.3 (C), 177.0 (C), 176.6 (C), 130.8 (C), 130.8 (C), 44.4 (CH), 43.4 (CH), 40.8 (CH), 40.6 (CH), 40.3 (CH), 39.2 (CH), 38.8 (CH), 33.7 (CH), 29.0 (CH), 25.0 (CH₃), 24.9 (CH₃), 24.8 (CH₃), 24.7 (CH₂), 24.4 (CH₂), 23.1 (CH₂), 16.5 (CH₃) ppm; 

IR (KBr disc) ν_max = 2961, 2948, 2842, 1770, 1695, 1435, 1383, 1286 cm^–1; 

LRMS (70 eV, EI) m/z (%) 453 ([M]^+•, 100%), 438 (7), 342 (33), 256 (14), 112 (39); 

HRMS calc for C₂₄H₂₇N₃O₆ [M]^+• 453.1900, found 453.1905.

Synthesis and Diels–Alder Reactivity of Substituted [4]Dendralenes

Mehmet F. Saglam^†, Ali R. Alborzi^†, Alan D. Payne^†, Anthony C. Willis^†, Michael N. Paddon-Row^‡, and Michael S. Sherburn^*†

^† Research School of Chemistry, The Australian National University, Canberra, ACT 2601, Australia

^‡ School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia

J. Org. Chem., Article ASAP

DOI: 10.1021/acs.joc.5b02583

Publication Date (Web): January 12, 2016

Copyright © 2016 American Chemical Society

*E-mail: michael.sherburn@anu.edu.au.

 http://pubs.acs.org/doi/full/10.1021/acs.joc.5b02583

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

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