Reaction of Highly Volatile Organic Compounds with Organolithium Species in Flow Microreactor

Kensuke Muta; Kazuhiro Okamoto; Aiichiro Nagaki

doi:10.1055/a-2170-2976

Synlett, Table of Contents

Synlett 2024; 35(11): 1259-1264
DOI: 10.1055/a-2170-2976

cluster

Japan/Netherlands Gratama Workshop

Reaction of Highly Volatile Organic Compounds with Organolithium Species in Flow Microreactor

Kensuke Muta

^aFundamental Chemical Research Center, Central Glass Co., Ltd., 17-5, Nakadai 2-chome, Kawagoe City, Saitama 350-1159, Japan

,

Kazuhiro Okamoto

^bDepartment of Chemistry, Graduate School of Science, Hokkaido University, Kita 10-jo, Nishi 8-chome, Kita-ku, Sapporo 060-0810, Japan

,

Aiichiro Nagaki ∗

^bDepartment of Chemistry, Graduate School of Science, Hokkaido University, Kita 10-jo, Nishi 8-chome, Kita-ku, Sapporo 060-0810, Japan

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Abstract

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Abstract

Highly volatile organic compounds (VOCs) with boiling points (bp) around or below room temperature are generally difficult to manipulate precisely in liquid-phase organic reactions although they offer significant atom-economic advantages. We have developed a novel approach using a jacketed syringe pump to enable the formylation of organolithium species in a continuous-flow system under ambient pressure. Methyl formate (bp 32 °C) worked as a formylating agent and was successfully delivered to the continuous operation for over 30 minutes in our microflow system. This methodology was successfully expanded to the application of acetaldehyde (bp 21 °C) and heptafluoropropyl bromide (bp 12 °C).

Key words

volatile organic compounds - organolithium species - flow chemistry - reactive intermediates - device control

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References

References and Notes
1 Technical Overview of Volatile Organic Compounds . US Environmental Protection Agency; Washington: 2023. https: //www.epa.gov/indoor–air-quality-iaq/technical-overview-volatile-organic-compounds#2
2 Salthammer T. Indoor Air 2016; 26: 25
3 Fu B, Zhuang X, Jiang G, Shi J, Lu Y. Environ. Sci. Technol. 2007; 41: 7597
4 Alexander M. Science 1981; 211: 132

For selected examples using autoclaves in a laboratory, see:

5a Ohashi M, Kambara T, Hatanaka T, Saijo H, Doi R, Ogoshi S. J. Am. Chem. Soc. 2011; 133: 3256
5b Trapasso G, Mazzi G, Chicharo B, Annatelli M, Dalla TD, Arico F. Org. Process Res. Dev. 2022; 26: 2830
5c White TD, Alt CA, Cole KP, Groh JM, Johnson MD, Miller RD. Org. Process Res. Dev. 2014; 18: 1482

For books and reviews on flow microreactor synthesis, see:

6a Microreactors in Organic Chemistry and Catalysis, 2nd ed. Wirth T. Wiley; Hoboken: 2013
6b Darvas F, Hessel V, Dorman G. Flow Chemistry 2014
6c Yoshida J. Basics of Flow Microreactor Synthesis 2015
6d Pastre JC, Browne DL, Ley SV. Chem. Soc. Rev. 2013; 42: 8849
6e Baxendale IR. J. Chem. Technol. Biotechnol. 2013; 88: 519
6f Fukuyama T, Totoki T, Ryu I. Green Chem. 2014; 16: 2042
6g Cambié D, Bottecchia C, Straathof NJ. W, Hessel V, Noël T. Chem. Rev. 2016; 116: 10276
6h Kobayashi S. Chem. Asian J. 2016; 11: 425
6i Degennaro L, Carlucci C, De Angelis S, Luisi R. J. Flow Chem. 2016; 6: 136
6j Plutschack MB, Pieber B, Gilmore K, Seeberger PH. Chem. Rev. 2017; 117: 11796
6k Cantillo D, Kappe CO. React. Chem. Eng. 2017; 2: 7
6l Zhao T, Micouin L, Piccardi R. Helv. Chim. Acta 2019; 102: e1900172
6m Power M, Alcock E, McGlacken GP. Org. Process Res. Dev. 2020; 24: 1814
6n Nagaki A, Ashikari Y, Takumi M, Tamaki T. Chem. Lett. 2021; 50: 485
6o Ashikari Y, Nagaki A. Synthesis 2021; 53: 1879
6p Fu WC, MacQueenac PM, Jamison TF. Chem. Soc. Rev. 2021; 50: 7378

For selected examples on microflow synthesis, see:

7a Islam M, Kariuki BM, Shafiq Z, Wirth T, Ahmed N. Eur. J. Org. Chem. 2019; 1371
7b Masui S, Manabe Y, Hirao K, Shimoyama A, Fukuyama T, Ryu I, Fukase K. Synlett 2019; 30: 397
7c Elsherbini M, Winterson B, Alharbi H, Folgueiras-Amador AA, Génot C, Wirth T. Angew. Chem. Int. Ed. 2019; 58: 9811
7d Ahn G.-N, Yu T, Lee H.-J, Gyak K.-W, Kang J.-H, You D, Kim D.-P. Lab Chip 2019; 19: 3535
7e Picard B, Pérez K, Lebleu T, Vuluga D, Burel F, Harrowven DC, Chataigner I, Maddaluno J, Legros J. J. Flow Chem. 2020; 10: 139
7f Laudadio G, Deng Y, van der Wal K, Ravelli D, Nuño M, Fagnoni M, Guthrie D, Sun Y, Noël T. Science 2020; 369: 92
7g Chatterjee S, Guidi M, Seeberger PH, Gilmore K. Nature 2020; 579: 379
7h Hoogendijk E, Swider E, Staal AH. J, White PB, van Riessen NK, Glaßer G, Lieberwirth I, Musyanovych A, Serra CA, Srinivas M, Koshkina O. ACS Appl. Mater. Interfaces 2020; 12: 49335
7i Sugisawa N, Sugisawa H, Otake Y, Krems RV, Nakamura H, Fuse S. Chem.: Methods 2021; 1: 484
7j Kondo M, Wathsala HD. P, Salem MS. H, Ishikawa K, Hara S, Takaai T, Washio T, Sasai H, Takizawa S. Commun. Chem. 2022; 5: 148
7k Miyamura H, Kobayashi S. Angew. Chem. Int. Ed. 2022; 61: e202201203

For selected examples of scale-up investigations in flow, see:

8a Sugita S, Ishitani H, Kobayashi S. Bull. Chem. Soc. Jpn. 2023; 96: 744
8b Harsany A, Conte A, Pichon L, Rabion A, Grenier S, Sandford G. Org. Process Res. Dev. 2017; 21: 273
8c Ötvös SB, Georgiádes Á, Mándity IM, Kiss L, Fülöp F. Beilstein J. Org. Chem. 2013; 9: 1508
8d Zhang Y, Born SC, Jensen KF. Org. Process Res. Dev. 2014; 18: 1476
8e Hafner A, Meisenbach M, Sedelmeier J. Org. Lett. 2016; 18: 3630
8f Mandai K, Yamamoto T, Mandai H, Nagaki A. Beilstein J. Org. Chem. 2022; 18: 660
8g Ashikari Y, Maekawa K, Takumi M, Tomiyasu N, Fujita C, Matsuyama K, Miyamoto R, Bai H, Nagaki A. Catal. Today 2022; 388–389: 231
8h Ashikari Y, Maekawa K, Ishibashi M, Fujita C, Shiosaki K, Bai H, Matsuyama K, Nagaki A. Green Process. Synth. 2021; 10: 722

For selected examples of environmentally friendly processes in flow, see:

9a Gemoets HP. L, Su Y, Shang M, Hessel V, Luque R, Noël T. Chem. Soc. Rev. 2016; 45: 83
9b Buglioni L, Raymenants F, Slattery A, Zondag SD. A, Noel T. Chem. Rev. 2016; 116: 9664
9c Frost CG, Mutton L. Green Chem. 2010; 12: 1687
9d Tamaki T, Nagaki A. Tetrahedron Lett. 2021; 81: 153364
9e Nakahara Y, Furusawa M, Endo Y, Shimazaki T, Takahashi Y, Jiang Y, Nagaki A. Chem. Eng. Technol. 2019; 42: 2154

For selected examples of our recent contributions to flash chemistry, see:

10a Ashikari Y, Saito K, Nokami T, Yoshida J, Nagaki A. Chem. Eur. J. 2019; 25: 15239
10b Wakabayashi S, Takumi M, Kamio S, Wakioka M, Ohki Y, Nagaki A. Chem. Eur. J. 2023; 29: e202202882
10c Okamoto K, Higuma R, Muta K, Fukumoto K, Tsuchihashi Y, Ashikari Y, Nagaki A. Chem. Eur. J. 2023; e202301738
10d Nakahara Y, Endo Y, Takahashi K, Kawaguchi T, Kato K, Matsuda Y, Nagaki A. Synthesis 2023; in press; DOI: 10.1055/a-2077-6187
10e Takumi M, Sakaue H, Nagaki A. Angew. Chem. Int. Ed. 2022; 61: e2021161
10f Takumi M, Sakaue H, Shibasaki D, Nagaki A. Chem. Commun. 2022; 58: 8344
10g Nagaki A, Ashikari Y, Takumi M, Tamaki T. Chem. Lett. 2021; 50: 485
10h Ashikari Y, Kawaguchi T, Mandai K, Aizawa Y, Nagaki A. J. Am. Chem. Soc. 2020; 142: 17039
10i Ichinari D, Ashikari Y, Mandai K, Aizawa Y, Yoshida J, Nagaki A. Angew. Chem. Int. Ed. 2020; 59: 1567
10j Colella M, Tota A, Takahashi Y, Higuma R, Ishikawa S, Degennaro L, Luisi R, Nagaki A. Angew. Chem. Int. Ed. 2020; 59: 10924

11 Mallia CJ, Baxendale IR. Org. Process Res. Dev. 2016; 20: 327

In general, N,N-dimethylformamide (DMF) is the standard choice for formylation reactions using organometallic reagents. Because methyl formate is a manufacturing feedstock of DMF, replacement of DMF is meaningful for industrial process research. See:

12a Hashmi AS. K. Sci. Synth. 2007; 25: 337
12b Kawasaki T, Matsumura Y, Tsutsumi T, Suzuki K, Ito M, Soai K. Science 2009; 324: 492
12c Prakash DJ, Xin L, Rai-Shung L. ACS Catal. 2018; 8: 9697
12d Wieteck M, Tokimizu Y, Rudolph M, Rominger F, Ohno H, Fujii N, Hashmi AS. K. Chem. Eur. J. 2014; 20: 16331

For papers on competitive consecutive reactions, see:

13a Fuoss RM. J. Am. Chem. Soc. 1943; 65: 2406
13b Friedman MH, White RR. AIChE J. 1962; 8: 581

14 Because of the rapid-mixing microflow system, we can avoid the lower temperature in generation of aryllithium species. See: Nagaki A, Hirose K, Moriwaki Y, Takumi M, Takahashi Y, Mitamura K, Matsukawa K, Ishizuka N, Yoshida J.-i. Catalysts 2019; 9: 300

We have previously emphasized the significance of mixing efficiency in controlling sequential reactions. See:

15a Nagaki A, Yamashita H, Hirose K, Tsuchihashi Y, Yoshida J. Angew. Chem. Int. Ed. 2019; 58: 4027
15b Kim H, Nagaki A, Yoshida J. Nat. Commun. 2011; 2: 264

16a Nagaki A, Kim H, Yoshida J. Angew. Chem. Int. Ed. 2008; 47: 7833
16b Nagaki A, Kim H, Moriwaki Y, Matsuo C, Yoshida J. Chem. Eur. J. 2010; 16: 11167
16c Nagaki A, Kim H, Yoshida J. Angew. Chem. Int. Ed. 2009; 48: 8063
16d Nagaki A, Kim H, Usutani H, Matsuo C, Yoshida J. Org. Biomol. Chem. 2010; 8: 1212
16e Nagaki A, Yamada S, Doi M, Tomida Y, Takabayashi N, Yoshida J. Green Chem. 2011; 13: 1110
16f Nagaki A, Yamada D, Yamada S, Doi M, Ichinari D, Tomida Y, Takabayashi N, Yoshida J. Aust. J. Chem. 2013; 66: 199
16g Nagaki A, Tokuoka S, Yamada S, Tomida Y, Oshiro K, Amii H, Yoshida J. Org. Biomol. Chem. 2011; 9: 1212

17a Lennox AJ. J, Lloyd-Jones GC. Chem. Soc. Rev. 2014; 43: 412
17b Rygus JP. G, Crudden CM. J. Am. Chem. Soc. 2017; 139: 18124

18a Horner L, Hoffmann HM. R, Wippel HG. Chem. Ber. 1958; 91: 61
18b Wadsworth WS. Jr, Emmons WD. J. Am. Chem. Soc. 1961; 83: 1733
18c Bisceglia JA, Orelli LR. Curr. Org. Synth. 2015; 19: 744

19a Maurya S, Yadav D, Pratapa K, Kumar A. Green Chem. 2017; 19: 629
19b Darwish KM, Salama I, Mostafa S, Gomaa MS, Khafagy ES, Helal MA. Bioorg. Med. Chem. Lett. 2018; 28: 1595

20 General Procedure: Solutions were continuously introduced to the flow microreactor system using syringe pumps (Harvard PHD2000 and TELEDYNE ISCO SyriXus 260x). A flow microreactor system consisting of two T-shaped micromixers (M1 and M2, φ = 250 or 500 μm), two microtube reactors (R1 and R2), and four tube precooling units were used. The flow microreactor system was dipped in a cooling bath₁ (T ₁ °C), and cooling bath₂ (T ₂ °C). After reaching a steady state, the outcoming solution was collected for 30 seconds in a vessel containing 4 mL of sat. aq. NH₄Cl. The yield was determined by GC analysis using undecane as an internal standard.

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