Continuous-Flow Preparation of γ-Butyrolactone Scaffolds, 2-(5,5-dimethyl-2-oxotetrahydrofuran-3- yl)acetic acid

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(5,5-dimethyl-2-oxotetrahydrofuran-3-yl)acetic acid

2-(5,5-Dimethyl-2-oxotetrahydrofuran-3-yl)acetic acid

2-carboxymethyl-4-methyl-4-pentanolide,

Cas 412298-86-3

2-(5,5-Dimethyl-2-oxotetrahydrofuran-3-yl)acetic acid (4a).

1H NMR (DMSO-d6, 400 MHz): δ = 3.20 – 3.10 (m, 1H), 2.62 (dd, J = 17.1, 4.4 Hz, 1H), 2.54 – 2.45 (m, 1H), 2.31 – 2.21 (m, 1H), 1.84 (t, J = 12.0 Hz, 1H), 1.39 (s, 3H), 1.33 (s, 3H) ppm.

13C NMR (DMSO-d6, 100.6 MHz): δ = 177.2, 172.5, 82.2, 39.8, 36.7, 34.0, 28.4, 26.6 ppm.

The 1H NMR data did not match those reported in the literature. S7 IR (neat): νmax = 2980, 2935, 1728, 1707 cm- 1 .

MP: 132.1-133.8 °C (lit.S8 137-140 °C).

[S7] Kochikyan, T. V.; Arutyunyan, E. V.; Arutyunyan, V. S.; Avetisyan, A. A. Russ. J. Org. Chem. 2002, 38, 390–393.

[S8] Phillips, D. D.; Johnson, W. A. J. Am. Chem. Soc. 1955, 77, 5977–5982.

ESI HRMS m/z C8H11O4 – [M-H]- : calcd 171.0652. Found 171.0653.

Continuous-Flow Preparation of γ-Butyrolactone Scaffolds from Renewable Fumaric and Itaconic Acids under Photosensitized Conditions

Romaric Gérardy^†, Marc Winter^‡, Clemens R. Horn^‡, Alessandra Vizza^‡, Kristof Van Hecke^§, and Jean-Christophe M. Monbaliu ^*^†

^† Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, B-4000 Liège (Sart Tilman), Belgium

^‡ Corning Reactor Technologies, Corning SAS, 7 bis Avenue de Valvins, CS 70156 Samois sur Seine, 77215 Avon Cedex, France

^§ XStruct, Department of Chemistry, Ghent University, Krijgslaan 281-S3, B-9000 Ghent, Belgium

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00314

*E-mail: jc.monbaliu@ulg.ac.be.

Abstract

The method and results described herein concern the photosensitized addition of various alcohols to renewable platform fumaric and itaconic acids under scalable continuous-flow conditions in glass micro- and mesofluidic reactors. Alcohols were used both as reagents and as solvents, thus contributing to a reduced environmental footprint. Process parameters such as the temperature, light intensity, and the nature as well as amount of the photosensitizer were assessed under microfluidic conditions and, next, transposed to a lab-scale mesofluidic reactor connected with an in-line NMR spectrometer for real-time reaction monitoring. Substituted γ-butyrolactones, including spiro derivatives with unique structural features, were obtained with quantitative conversion of the starting materials and in 47–76% isolated yields. The model photoaddition of isopropanol to fumaric acid was next successfully transposed in a pilot-scale continuous-flow photoreactor to further demonstrate scalability.

JC M. Monbaliu, PhD.
Department of Chemistryjc.monbaliu@ulg.ac.be
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