Journal of Flow Chemistry

, Volume 8, Issue 1, pp 29–34 | Cite as

A continuous-flow procedure for the synthesis of 4-Benzylidene-pyrazol-5-one derivatives

  • Jiangang Yu
  • Jianguo Xu
  • Jie Li
  • Yi Jin
  • Wanghui Xu
  • Zhiqun Yu
  • Yanwen Lv
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Abstract

A two-step flow reactor has been set up for an expeditious synthesis of 4-benzylidene-pyrazol-5-one derivatives. This procedure involved cyclization of aromatic hydrazine/β-keto ester and subsequent Knoevenagel condensation reaction with aromatic aldehydes in tandem without isolation of intermediates. Residence time was reduced to less than 2 min in total through conducting this reaction at a relatively high temperature. Accordingly, 15 samples were achieved and isolated in moderate to excellent yields.

Graphical abstract

Keywords

Continuous-flow chemistry 4-Benzylidene-pyrazol-5-one Knoevenagel condensation 

Introduction

Pyrazolones are important N-heterocyclic compounds which display variant pharmaceutical activities [1, 2]. Consequently, they are widely utilized in medicinal chemistry and investigated in organic synthesis. They serve as not only anti-cancer drugs [3], anti-inflammatory agents [4], but also insecticides [5], herbicides [6]. Besides, pyrazolones are excellent chelating and extracting reagents for different metal ions and dyestuffs [7]. For that, an efficient synthesis of pyrazolones is extremely attractive and interesting to the fields of both pharmaceutical chemistry and agronomy.

Generally, 4-benzylidene-pyrazol-5-one derivatives (V) are prepared in two step: a cyclization of arylhydrazines (I) and β-keto estercyclization (II) plus a Knoevenagel condensation of 1-aryl-pyrazol-5-one (III) and aldehydes (IV) as shown in Scheme 1 [8, 9]. Recently, some new protocols such as microwave-irradiated [10, 11], ultrasound-assisted [12], solid-state [13], ionic liquid-mediated [14], microreactors-intensfied [15, 16, 17, 18, 19], etc. have been applied to facilitate this transformation. However, some problems like low reaction rate, yields, selectivity, and the use of toxic solvents or expensive catalysts still exist to prevent its further development [20, 21].
Scheme 1

Synthesis of 4-benzylidene-pyrazol-5-one derivatives

During the last decade, continuous-flow technology has attracted considerable attention in the organic chemistry community [22, 23, 24, 25, 26, 27, 28, 29, 30]. It possesses several advantages over the traditional batch vessels, such as, better mass and heat transfer, fewer transport limitations, safer process, easier scaling-up and more precise control of reaction variables [31, 32, 33, 34]. In our previous study, the synthetic process of indoles was successfully intensified by means of the continuous-flow technology [35, 36, 37]. In light of our end-to-end design of the reactors, the yields and selectivities of those procedures were highly improved. In this study, we have designed a continuous-flow reactor which is appropriate for a tandem reaction of cyclization and Knoevenagel condensation [38, 39, 40, 41, 42, 43, 44, 45] in a single stage to safely and expeditiously synthesize 4-benzylidene-pyrazol-5-one derivatives.

Results and discussion

Continuous-flow cyclization

Phenylhydrazine (Ia, Scheme 2) was initially chosen as a model compound to study its reactive behavior in continuous-flow reactors (as shown in Fig. 1). The continuous-flow cyclization equipment consists of two peristaltic pumps (P1, P2,) which were connected by a T-joint (1 mm i.d., SS316). The jointed line was linked to a coil (1.5 mm i.d., SS316) which was immersed in a thermostat controlled oil bath. The stream was then collected by container, which had appropriate amount of ice water. Solids were immediately precipitated, collected and purified by chromatography column to give the desired product (IIIa, Scheme 2).
Scheme 2

The synthesis of compound IIIa from Ia and II

Fig. 1

Continuous-flow setup for the reaction of phenylhydrazine and methyl acetoacetate

The reaction was initially carried out at moderate temperatures. When we tried some solvents with low boiling point (such as methanol), conversion was relatively low, even if the residence time was prolonged to 10 min. In order to achieve a rapid reaction, we tried ethylene glycol which has high boiling point and simultaneously with the capability of high reaction temperature. As shown in Fig. 2, the reaction rate increase accordingly as the raise of the reaction temperature. When the reaction temperature reach 160 °C, the reaction only needs less than 1 min to complete with an over 99% isolated yield of product IIIa.
Fig. 2

Effect of temperature on the cyclization reaction (60~75 °C methanol as solvent, 100~180 °C ethylene glycol as solvent)

Continuous-flow Knoevenagel condensation

Knoevenagel condensation reaction was performed in the same device (Fig. 1). A solution of 1-phenyl-3-methyl-5-pyrazolone (IIIa) in ethylene glycol directly prepared from step one and a solution of indole-3-carboxaldehyde (IV1, 0.2 M) were pumped into the reactor by two pumps respectively. Flow rates were adjusted to maintain the same molar flow rate ratio. After a residence time in reacting tube, the mixture flowed through the outlet and streams were collected for analysis. To simplify the optimization process and explore the possibility of a two-step continuous flow procedure, we directly applied the same condition of cyclization step to the condensation reaction. Fortunately, it only takes 1 min to complete the reaction with an isolated yield of about 98% of product Va,1 was obtained under these conditions (Scheme 3).
Scheme 3

The synthesis of compound Va,1 from IIIa and IV1

Continuous-flow cyclization and Knoevenagel condensation in tandem

Inspired by the work as above, we tried to find a way to connect them in the following work. As showed in Fig. 3, solution A and solution B were simultaneously pumped into tube I by P 1 and P 2 , respectively with a residence time of 1 min, then the produced solution and a solution of indole-3-carboxaldehyde (IV1) were flowed into tube II at the same time, the molar flow rate ratio of three materials was 1: 1: 1. After another residence time of 1 min, the mixture flowed into the container, which had appropriate amount of ice water. Solids were precipitated immediately, collected to obtain crude product. It was then purified by column chromatography to obtain the target compound Va1 with an isolated yield of 96%. So far, a continuous, high efficiency and catalyst-free two-step flow procedure for synthesis of Va,1 was established.
Fig. 3.

Two-step continuous flow synthesis set-up (A is 0.2 M phenylhydrazine in ethylene glycol, B is 0.2 M methyl acetoacetate in ethylene glycol, C is 0.2 M indole-3-carboxaldehyde in ethylene glycol)

In order to verify the versatility and suitability of different substrates, a series of aromatic hydrazines and aromatic aldehydes were also studied as shown in Table 1. The isolated yield which are mostly higher than indicates the good versatility of this reaction.
Table 1

Synthesis of Va-f,1–10 in continuous flow reactor

aAll reactions were performed on a 100 mmol scale

bIsolated yields of V were calculated from I

Comparison of batch and continuous-flow procedure

In order to compare a typical batch with flow reaction, target compound Va,1 was also be synthesized in batch (Scheme 4), using analogous conditions (0.2 M phenylhydrazine ethylene glycol solution and 0.2 M methyl acetoacetate solution were heated to 160 °C separately, then poured into a flask rapidly, stirred for 1 min, and then a 0.5 M solution of indole-3-carboxaldehyde was poured, stirred for another 1 min, then put the flask into ice water and added ice into the reactor to quench the reaction) to those used in flow system. In the scale of 1 mmol phenylhydrazine, isolated yield of batch and flow were basically the same. In the scale of 10 mmol phenylhydrazine, yield of I-1 in batch reaction decreased slightly (95% isolated yield) and side products such as hydrazones was found. They mainly generated from uncyclized intermediates and the reaction of unreacted hydrazine with the added aldehyde. In the scale of 100 mmol phenylhydrazine, more amount of side products (Scheme 5, totally excess than 10%) that hardly spotted in flow reaction emerged. The improvements were achieved in the flow manner, due to the precise control of reaction parameters, good mass and heat transfer, no scale-up effect that flow system offers.
Scheme 4

Typical batch comparison

Scheme 5

Byproducts generated in batch manner

Experimental section

General

All chemicals and solvents were purchased from reagent companies like aladdin (a Chinese chemical reagents supplier) and used directly without any further purification. Melting points were determined on Buchi 540 melting point apparatus and are uncorrected. 1H NMR spectra was recorded on Varian 400 MHz spectrometer using tetramethylsilane (TMS) as internal standard. Elemental analyses were performed on vario MACRO.

Typical continuous procedure

Solution A (500 mL of ethylene glycol solution containing 100 mmol aromatic hydrazine, and solution B (500 mL of ethylene glycol solution containing 100 mmol methyl acetoacetate) were pumped into the T-joint at 10 mL/min respectively, after a residence time of about 1 min at 160 °C in reacting tube I, solution C (500 mL of ethylene glycol solution containing 100 mmol aromatic aldehyde) was pumped into another T-mixer at 10 mL/min, after another residence time of 1 min at 160 °C in reacting tube II, mixture flowed through the outlet and accumulated in the container. Reaction was quenched by ice water. The solid was filtered with suction after the slurry was cooled to room temperature. The solid was dried in vacuo to yield the target compound.

Typical batch experiment

Batch reaction for Va,1 (Table 1, entry 1) in 10 mmol scale: 50 mL of ethylene glycol solution containing 10 mmol phenylhydrazine, and 50 mL of ethylene glycol solution containing 10 mmol methyl acetoacetate were heated to 160 °C separately, then poured into a 250 mL flask rapidly, vigorous mechanical stirring for 1 min, 50 mL of ethylene glycol solution containing 10 mmol indole-3-carboxaldehyde was poured, stirred for another 1 min, then put the flask into ice water and added ice into the reactor to quench the reaction. The solid was filtered with suction and dried in vacuo to obtain the target compound.
  • (E)-4-((1H–indol-3-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (Va,1) [46, 47]

M.p. 234–236 °C. MS (ESI): 302.0 [M + H]+. 1H NMR (400 MHz, CDCl3) δ/ppm:9.98 (s, 1H), 9.34 (s, 1H), 7.92–7.71 (m,3H), 7.48–8.44 (m, 3H), 7.25 (t, 1H, J = 5.2 Hz), 7.14–7.06 (m,3H), 2.60 (s, 3H).
  • (E)-4-((1H–indol-3-yl)methylene)-1-(2-ethylphenyl)-3-methyl-1H-pyrazol-5(4H)-one (Vb,1)

M.p. 272–273 °C. MS (ESI) 330 [M + H]+. 1H NMR (400 MHz, d 6 -DMSO) δ/ppm:12.38 (s, 1H), 9.60 (d, 1H, J = 3.2 Hz), 8.00–7.98 (m, 1H), 7.94 (s, 1H), 7.42–7.39 (m, 1H), 7.21–7.11 (m, 6H), 2.43 (q, 2H, J = 7.6 Hz), 2.22 (s, 3H), 0.93 (t, 3H, J = 7.6 Hz). Elem anal. Calcd for C21H19N3O: C, 76.57; H, 5.81; N, 12.76. Found: C, 76.32; H, 5.98, N, 12.55.
  • (E)-4-((1H–indol-3-yl)methylene)-1-(2-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (Vc,1) [46, 47]

M.p. 260–261 °C. MS (ESI) 318 [M - H]. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 12.58 (s, 1H), 9.73 (s, 1H), 8.16–8.11 (m, 2H), 7.58–7.45 (m, 4H), 7.31–7.17 (m, 3H), 2.38 (s, 3H).
  • (E)-4-((1H–indol-3-yl)methylene)-1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (Vd,1) [46, 47]

M.p. 269–270 °C. MS (ESI) 318 [M - H]. 1H NMR (400 MHz, CDCl3) δ/ppm: 9.97 (s, 1H), 9.31 (s, 1H), 7.96–7.87 (m, 5H), 7.44–7.35 (m, 3H), 7.11 (s, 1H), 2.44 (s, 3H).
  • (E)-4-((1H–indol-3-yl)methylene)-1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (Ve,1) [46, 47]

M.p. 283-284 °C. MS (ESI) 334 [M - H]. 1H NMR (400 MHz, CDCl3) δ/ppm: 10.17 (s, 1H), 9.46 (s, 1H), 8.06–7.95 (m, 5H), 7.52–7.44 (m, 3H), 7.25 (s, 1H), 2.48 (s, 3H).
  • (E)-4-((1H–indol-3-yl)methylene)-1-(2,4-difluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (Vf,1)

M.p. 299–231 °C. MS (ESI) 336 [M - H]. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 12.55(s, 1H), 9.69 (s, 1H), 8.11–8.07 (m, 2H), 7.55–7.52 (m, 2H), 7.43–7.15 (m, 4H), 2.37 (s, 3H). Elem anal. Calcd for C19H13F2N3O: C, 67.65; H, 3.88; N, 12.46. Found: C, 67.85; H, 3.11, N, 12.50.
  • (E)-4-benzylidene-1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (Vd,2)

M.p.149-150 °C. MS (ESI) 281 [M + H]+. 1H NMR (400 MHz, CDCl3) δ/ppm: 8.45 (d, 2H, J = 7.2 Hz), 7.91–7.88 (m, 2H), 7.53–7.48 (m, 3H), 7.37 (s, 1H), 7.09–7.05 (m, 2H), 2.34 (s, 3H). Elem anal. Calcd for C17H13FN2O: C, 72.85; H, 4.67; N, 9.99. Found: C, 80.12; H, 4.28, N, 10.04.
  • (E)-1-(4-fluorophenyl)-3-methyl-4-(4-methylbenzylidene)-1H–pyrazol-5(4H)-one (Vd,3) [48, 49]

M.p. 168-169 °C. MS (ESI) 295 [M + H]+. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.72–8.68 (m, 2H), 7.92–7.89 (m, 2H), 7.83 (s, 1H), 7.41 (t, 2H, J = 8.4 Hz), 7.25 (t, 2H, J = 8.4 Hz), 2,39 (s, 3H), 2.33 (s, 3H).
  • (E)-1-(4-fluorophenyl)-4-(4-methoxybenzylidene)-3-methyl-1H-pyrazol-5(4H)-one (Vd,4)

M.p. 155-156 °C. MS (ESI) 311 [M + H]+. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.67 (d, 2H, J = 5.2 Hz),7.92–7.89(m, 2H),7.71 (s, 1H), 7.24 (t, 2H, J = 8.8 Hz),7.09 (d, 2H, J = 9.2 Hz), 3.87 (s, 3H), 2.30 (s, 3H). Elem anal. Calcd for C18H15FN2O2: C, 69.67; H, 4.87; N, 9.03. Found: C, 70.01; H, 5.06, N, 8.87.
  • (E)-1-(4-fluorophenyl)-4-(4-hydroxybenzylidene)-3-methyl-1H-pyrazol-5(4H)-one (Vd,5)

M.p. 273-275 °C. MS (ESI) 295 [M - H]. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.54 (d, 2H, J = 5.2 Hz), 7.91–7.87 (m, 2H), 7.70 (s, 1H), 7.25 (t, 2H, J = 8.8 Hz), 6.89 (d, 2H, J = 9.2 Hz), 2.29 (s, 3H). Elem anal. Calcd for C17H13FN2O2: C, 68.91; H, 4.42; N, 9.45. Found: C, 69.02; H, 4.05, N, 9.81.
  • (E)-4-(4-fluorobenzylidene)-1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (Vd,6)

M.p. 175-177 °C. MS (ESI) 299 [M + H]+. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.71–8.67 (m, 2H), 7.91–7.87 (m, 2H), 7.83 (s, 1H),7.40 (t, 2H, J = 8.4 Hz), 7.26 (t, 2H, J = 8.4 Hz), 2.33 (s, 3H). Elem anal. Calcd for C17H12F2N2O: C, 68.45; H, 4.05; N, 9.39. Found: C, 68.09; H, 3.86, N, 9.05.
  • (E)-4-(2-fluorobenzylidene)-1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (Vd,7)

M.p. 148-149 °C. MS (ESI) 299 [M + H]+. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.86–8.82 (m, 1H), 7.91–7.79 (m, 3H), 7.64 (s, 1H), 7.36–7.33 (m, 2H), 7.27–7.20 (m, 2H), 2.32 (s, 3H). Elem anal. Calcd for C17H12F2N2O: C, 68.45; H, 4.05; N, 9.39. Found: C, 68.32; H, 4.21, N, 9.55.
  • (E)-1-(4-fluorophenyl)-3-methyl-4-(naphthalen-1-ylmethylene)-1H–pyrazol-5(4H)-one (Vd,8)

M.p. 144-145 °C. MS (ESI) 331 [M + H]+. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.62 (d, 1H, J = 7.2 Hz), 8.45 (s, 1H), 8.28 (d, 1H, J = 7.6 Hz), 8.11 (d, 2H, J = 4.0 Hz), 8.00 d, 2H, J = 4.0 Hz), 7.86–7.83 (m, 2H), 7.66–7.56 (m, 3H), 7.21 (t, 2H, J = 8.8 Hz),2.41 (s, 3H). Elem anal. Calcd for C21H15FN2O: C, 76.35; H, 4.58; N, 8.48. Found: C, 76.06; H, 4.22, N, 8.56.
  • (E)-4-(anthracen-9-ylmethylene)-1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5(4H)-one(Vd,9)

M.p. 193-194 °C. MS (ESI) 381 [M + H]+. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.36 (s, 1H), 7.89 (d, 2H, J = 5.6 Hz), 7.85 (s, 1H), 7.70 (d, 2H, J = 5.6 Hz), 7.40–7.32 (m, 6H), 7.20 (t, 2H, J = 6.0 Hz), 2.30 (s, 3H). Elem anal. Calcd for C25H17FN2O: C, 78.93; H, 4.50; N, 7.36. Found: C, 79.05; H, 4.68, N, 7.50.
  • (E)-1-(4-fluorophenyl)-3-methyl-4-(4-nitrobenzylidene)-1H–pyrazol-5(4H)-one (Vd,10) [48, 49]

M.p. 241-243 °C. MS (ESI) 326 [M + H]+. 1H NMR (400 MHz, d6-DMSO) δ/ppm: 8.52 (d, 2H, J = 8.0 Hz), 8.20 (d, 2H, J = 8.8 Hz), 7.82 (s, 1H), 7.73–7.70 (m, 2H), 7.15–7.10 (m, 2H), 2.21 (s, 3H).

Conclusion

In conclusion, a reliable and safe procedure for synthesis of 4-benzylidene-pyrazol-5-one derivatives via a two-step continuous flow system has been developed. The precise control of the reaction variables using the flow technique significantly improved the yield and selectivity over the corresponding batch procedures. The productivity of 4-benzylidene-pyrazol-5-one derivatives was calculated to be 2 mmol/min in this developed flow system.

Notes

Acknowledgments

Financial support from the National Science Foundation of China (21476128) is gratefully acknowledged.

Supplementary material

41981_2018_3_MOESM1_ESM.doc (19.1 mb)
ESM 1 (DOC 19562 kb)

References

  1. 1.
    A. Weissberger. In: Wiley, R. H., Wiley, P. (eds.) The Chemistry of Heterocyclic Compounds: Pyrazolinones, Pyrazolidones and Derivatives. Wiley, New York; 1964Google Scholar
  2. 2.
    S. Scheibye, A. A. El-Barbary, S. O. Lawesson, H. Fritz, G. Rihs. Tetrahedron 1982; 38, 3753Google Scholar
  3. 3.
    Y. Kakiuchi, N. Sasaki, M. Satoh-Masuoka, H. Murofushi, Murakami-Murofushi, K. Biochem. Biophys. Res. Commun. 2004; 320, 1351Google Scholar
  4. 4.
    S. P. Hiremath, K. Rudresh, A. R. Saundane. Indian J. Chem. 2002; 41B, 394Google Scholar
  5. 5.
    In: H. A. Lubs (ed.) The Chemistry of Synthetic Dyes and Pigments. American Chemical Society, Washington, DC; 1970Google Scholar
  6. 6.
    Joerg S, Reinhold G, Joachim OS, Robert S, Klaus L, Offen G (1988) Chem Abstr 108:167465 DE3, 625Google Scholar
  7. 7.
    A. B. Uzoukwu. Polyhedron 1993; 12, 2719Google Scholar
  8. 8.
    G. Desimoni, L. Astolfi, M. Cambieri, A. Gamber, G. Tacconi. Tetrahedron 1973; 29, 2627Google Scholar
  9. 9.
    W. S. Hamama. Synth. Commun. 2001; 31, 1335Google Scholar
  10. 10.
    M. M. Mojtahedi, M. R. Jalali, M. S. Abaee, M. Bolourtchian. Heterocycl. Commun. 2006; 12, 225Google Scholar
  11. 11.
    B. R. Vaddula, R. S. Varma, J. Leazer. Tetrhedron Lett. 2013; 54, 1538Google Scholar
  12. 12.
    M. M. Mojtahedi, M. Javadpour, M. S. Abaee. Ultrason. Sonochem. 2008; 15, 828Google Scholar
  13. 13.
    M. X. Guo, J. X. Guo, D. Z. Jia, H. Liu, L. Liu, A. J. Liu, F. Li. J. Mol. Struct. 2013; 1035, 271Google Scholar
  14. 14.
    Ahmad N (2011) Acta Ciencia Indica. Chemistry 37:5Google Scholar
  15. 15.
    E. Garcia-Egido, S. Y. Wong, B. H. Warrington. Lab Chip 2002; 2, 31Google Scholar
  16. 16.
    M. Fernandez-Suarez, S. Y. Wong, B. H. Warrington. Lab Chip 2002; 2, 170Google Scholar
  17. 17.
    E. Garcia-Egido, V. Spikmans, S. Y. Wong, B. H. Warrington. Lab Chip 2003; 3, 73Google Scholar
  18. 18.
    D. Obermayer, T. N. Glasnov, C. O. Kappe. J. Org. Chem. 2011; 76, 6657Google Scholar
  19. 19.
    J. Pelleter, F. Renaud. Org. Process. Res. Dev. 2009; 13, 698Google Scholar
  20. 20.
    M. S. K. Youssef, S. A. M. Metwally, M. A. El-Mahraby, M. I. Younes. J. Heterocyclic Chem. 1984; 21, 1747Google Scholar
  21. 21.
    P. Sun, D. Yang, W. Wei, X. Sun, W. Zhang, H. Zhang, Y. Wang, H. Wang. Tetrahedron 2017; 73, 2022Google Scholar
  22. 22.
    V. Hessel (2009). Chem. Eng. Technol. 32, 1655Google Scholar
  23. 23.
    B. Wahab, G. Ellames, S. Passey, P. Watts (2010). Tetrahedron 66, 3861Google Scholar
  24. 24.
    E. Riva, S. Gagliardi, C. Mazzoni, D. Passarella, A. Rencurosi, D. Vigo, A. Rencurosi (2010). Tetrahedron 66, 3242Google Scholar
  25. 25.
    Z. Q. Yu, Y. W. Lv, C. M. Yu (2012). Org. Process. Res. Dev. 16, 1669Google Scholar
  26. 26.
    J. Wegner, S. Ceylan, A. Kirschning. Adv. Synth. Catal. 2012; 354, 17Google Scholar
  27. 27.
    C. Wiles, P. Watts. Green Chem. 2012; 14, 38Google Scholar
  28. 28.
    Z. Q. Yu, Y. W. Lv, C. M. Yu, W. K. Su. Tendrahedron Lett. 2013; 54, 1261Google Scholar
  29. 29.
    Z. Q. Yu, Y. W. Lv, C. M. Yu, W. K. Su. Org. Process Res. Dev. 2013; 17, 438Google Scholar
  30. 30.
    C. Wiles, P. Watts. Green Chem. 2014; 16, 55Google Scholar
  31. 31.
    D. Cambié, C. Bottecchia, N. J. W. Straathof, V. Hessel and T. Noël. Chem. Rev. 2016; 116, 10276Google Scholar
  32. 32.
    B. Gutmann, D. Cantillo and C. O. Kappe. Angew. Chem. Int. Ed. 2015; 54, 6688–6728Google Scholar
  33. 33.
    J. Britton. J. Flow Chem. 2016; 6, 123Google Scholar
  34. 34.
    S. Chada, D. Mandala and P. Watts. J. Flow Chem. 2017; 7, 37Google Scholar
  35. 35.
    Y. W. Lv, Z. Q. Yu, W. K. Su. Org. Process. Res. Dev. 2011; 15, 471Google Scholar
  36. 36.
    J. Yu, J. Xu, Z. Yu, Y. Jin, J. Li, Y. Lv. J. Flow Chem. 2017; 7, 33Google Scholar
  37. 37.
    J. Xu, J. Yu, Y. Jin, J. Li, Z. Yu, Y. Lv. Chem. Eng. Process 2017; 121, 144Google Scholar
  38. 38.
    W. P. Bula, W. Verboom, D. N. Reinhoudt, H. J. G. E. Gardeniers. Lab Chip 2007; 7, 1717Google Scholar
  39. 39.
    E. G. Moschetta, S. Negretti, K. M. Chepiga, N. A. Brunelli, Y. Labreche, Y. Feng, F. Rezaei, R. P. Lively, W. J. Koros, H. M. L. Davies, C. W. Jones. Angew. Chem. Int. Ed. 2015; 54, 6470Google Scholar
  40. 40.
    M. Lopez-Pastor, A. Dominguez-Vidal, M. J. Ayora-Canada, T. Laurell, M. Valcarcel, B. Lendl. Lab Chip 2007; 7, 126Google Scholar
  41. 41.
    H. Seyler, S. Haid, T.-H. Kwon, D. J. Jones, P. Baeuerle, A. B. Holmes, W. W. H. Wong. Aust. J. Chem. 2013; 66, 151Google Scholar
  42. 42.
    V. Pandarus, G. Gingras, F. Beland, R. Ciriminna, M. Pagliaro. Catal. Sci. Technol. 2011; 1, 1600Google Scholar
  43. 43.
    M. Tarleton, A. McCluskey. Tetrahedron Lett. 2011; 52, 1583Google Scholar
  44. 44.
    N. Nikbin, P. Watts. Org. Process. Res. Dev. 2004; 8, 942Google Scholar
  45. 45.
    R. Munirathinam, J. Huskens, W. Verboom. Adv. Synth. Catal. 2015; 357, 1093Google Scholar
  46. 46.
    K. Suzdalev, M. Babakova. Russ. J. Org. Chem. 2005; 41, 233Google Scholar
  47. 47.
    Z. Han, X. Liang, Y. Wang, J. Qing, L. Cao, L. Shang, Z. Yin. Eur. J. Med. Chem. 2016; 116, 147Google Scholar
  48. 48.
    R. Ramajayam, K.-P. Tan, H.-G. Liu, P.-H. Liang, Bioorg. Med. Chem. 2010; 18, 7849Google Scholar
  49. 49.
    M. Parveen, S. Azaz, A. M. Malla, F. Ahmad, M. Ahmad, M. Gupta. RSC Adv. 2016; 6, 148Google Scholar

Copyright information

© Akadémiai Kiadó 2018

Authors and Affiliations

  • Jiangang Yu
    • 1
  • Jianguo Xu
    • 1
  • Jie Li
    • 1
  • Yi Jin
    • 1
  • Wanghui Xu
    • 1
  • Zhiqun Yu
    • 2
  • Yanwen Lv
    • 1
  1. 1.College of Chemical and Material EngineeringQuzhou UniversityQuzhouPeople’s Republic of China
  2. 2.Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical SciencesZhejiang University of TechnologyHangzhouPeople’s Republic of China

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