Synthesis of Fluorinated 2-Benzylphthalazin-1(2H)-one, 1-Phthalazinamine, and 1-Alkoxy/Benzyloxyphthalazine Derivatives by an Ultrasonication Method

Mohanreddy Pothireddy; Gurupada Hazra; Penke Vijaya Babu; Barla Thirupathi; Rambabu Dandela

doi:10.1055/a-1846-5200

Synlett, Table of Contents

Synlett 2022; 33(17): 1716-1722
DOI: 10.1055/a-1846-5200

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Chemical Synthesis and Catalysis in India

Synthesis of Fluorinated 2-Benzylphthalazin-1(2H)-one, 1-Phthalazinamine, and 1-Alkoxy/Benzyloxyphthalazine Derivatives by an Ultrasonication Method

Mohanreddy Pothireddy

^aDepartment of Industrial and Engineering Chemistry, Institute of Chemical Technology, Indianoil Odisha Campus, Samantpuri, Bhubaneswar 751013, Odisha, India

,

Gurupada Hazra

^bDepartment of Chemical Sciences, Indian Institute of Science Education and Research Berhampur, Transit Campus, Govt. ITI Building, NH 59, Engineering School Road, Ganjam District, Berhampur 760 010, Odisha, India

,

Penke Vijaya Babu

^cDr. Reddys Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500046, India

,

Barla Thirupathi ∗

^bDepartment of Chemical Sciences, Indian Institute of Science Education and Research Berhampur, Transit Campus, Govt. ITI Building, NH 59, Engineering School Road, Ganjam District, Berhampur 760 010, Odisha, India

,

Rambabu Dandela∗

^aDepartment of Industrial and Engineering Chemistry, Institute of Chemical Technology, Indianoil Odisha Campus, Samantpuri, Bhubaneswar 751013, Odisha, India

› Author Affiliations

Abstract

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Abstract

Fluorinated heterocyclic compounds have been proven to exhibit interesting potential biological activities. Therefore, various fluorinated 2-benzylphthalazine-1(2H)-one and phthalazine-1-amine derivatives and nonfluorinated 1-alkoxy/benzyloxyphthalazines derivatives have been synthesized by an ultrasonication method. This protocol is more efficient than the conventional method in terms of its product yield and reaction handling and timelines.

Key words

ultrasound - sonochemistry - fluorinated heterocycles - benzylphthalazinones - phthalazinamines - phthalazines

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References

References and Notes

1a Sanderson B. J. Chem. Technol. Biotechnol. 2004; 79: 207
1b Luche J.-L. Synthetic Organic Sonochemistry . Springer US; New York: 1998

2 Cravotto G, Cintas P. Chem. Soc. Rev. 2006; 35: 180
3 Martínez RF, Cravotto G, Cintas P. J. Org. Chem. 2021; 86: 13833
4 Low CM. R. Ultrason. Sonochem. 1995; 2: S153
5 Ley SV, Low CM. R. Ultrasound in Synthesis . Springer; Berlin: 1989
6 Jayarajan R, Chandrashekar HB, Dalvi AK, Maiti D. Chem. Eur. J. 2020; 26: 11426
7 Cintas P, Barge A, Tagliapietra S, Boffa L, Cravotto G. Nat. Protoc. 2010; 5: 607
8 May PA, Moore JS. Chem. Soc. Rev. 2013; 42: 7497
9 Nakamura E, Imanishi Y, Machii D. J. Org. Chem. 1994; 59: 8178
10 Cella R, Stefani HA. Tetrahedron 2009; 65: 2619
11 Hekal MH, El-Naggar AM, Abu El-Azm FS. M, El-Sayed WM. RSC Adv. 2020; 10: 3675

12a Ramarao S, Pothireddy M, Venkateshwarlu R, Moturu KM. V, Siddaiah V, Dandela R, Pal M. J. Mol. Struct. 2022; 1254: 132418
12b Pothireddy M, Bhukta S, Babu PJ, Thirupathi B, Dandela R. Synth. Commun. 2022; 52: 564

13 Haider N, Holzer W. Science of Synthesis . Yamamoto Y. Thieme; Stuttgart: 2004. Vol. 16, Chap. 16.10 315
14 Marzouk MI, Shaker SA, Abdel Hafiz AA, El-Baghdady KZ. Biol. Pharm. Bull. 2016; 39: 239
15 Mylari BL, Larson ER, Beyer TA, Zembrowski WJ, Aldinger CE, Dee MF, Siegel TW, Singleton DH. J. Med. Chem. 1991; 34: 108
16 Ward WH, Sennitt CM, Ross H, Dingle A, Timms D, Mirrlees DJ, Tuffin DP. Biochem. Pharmacol. 1990; 39: 337
17 Engel J, Bork A, Fleischhauer I, Kutscher B, Liefländer M. J. Prakt. Chem./Chem.-Ztg. 1994; 336: 207
18 Ran J.-H, Li M, Tou W.-I, Lei T.-L, Zhou H, Chen CY.-C, Yang B.-X. Zhongguo Yaoli Xuebao 2016; 37: 973
19 Medda F, Sells E, Chang H.-H, Dietrich J, Chappeta S, Smith B, Gokhale V, Meuillet EJ, Hulme C. Bioorg. Med. Chem. Lett. 2013; 23: 528
20 Sánchez-Moreno M, Gómez-Contreras F, Navarro P, Marín C, Ramírez-Macías I, Olmo F, Sanz AM, Campayo L, Cano C, Yunta MJ. R. J. Antimicrob. Chemother. 2012; 67: 387
21 Elmeligie S, Aboul-Magd AM, Lasheen DS, Ibrahim TM, Abdelghany TM, Khojah SM, Abouzid KA. M. J. Enzyme Inhib. Med. Chem. 2019; 34: 1347
22 Amin KM, Barsoum FF, Awadallah FM, Mohamed NE. Eur. J. Med. Chem. 2016; 123: 191

23a Han J, Remete AM, Dobson LS, Kiss L, Izawa K, Moriwaki H, Soloshonok VA, O’Hagan D. J. Fluorine Chem. 2020; 239: 109639
23b Fujiwara T, O’Hagan D. J. Fluorine Chem. 2014; 167: 16

24 del Olmo E, Barboza B, Ybarra MI, López-Pérez JL, Carrón R, Sevilla MA, Boselli C, San Feliciano A. Bioorg. Med. Chem. Lett. 2006; 16: 2786
25 Saranya S, Radhika S, Afsina Abdulla CM, Anilkumar G. J. Heterocycl. Chem. 2021; 58: 1570
26 CCDC 2150995, 2150994, and 2132768 contain the supplementary crystallographic data for compounds 3c, 6b, and 7a, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
27 Colombano G, Travelli C, Galli U, Caldarelli A, Chini MG, Canonico PL, Sorba G, Bifulco G, Tron GC, Genazzani AA. J. Med. Chem. 2010; 53: 616

28a Sánchez-Moreno M, Sanz AM, Gómez-Contreras F, Navarro P, Marín C, Ramírez-Macias I, Rosales MJ, Olmo F, Garcia-Aranda I, Campayo L, Cano C, Arrebola F, Yunta MJ. R. J. Med. Chem. 2011; 54: 970
28b Sanz AM, Gómez-Contreras F, Navarro P, Sánchez-Moreno M, Boutaleb-Charki S, Campuzano J, Pardo M, Osuna A, Cano C, Yunta MJ. R, Campayo L. J. Med. Chem. 2008; 51: 1962

29 Rizk SA, Abdelwahab SS, El-Badawy AA. J. Heterocycl. Chem. 2019; 56: 2347
30 Bian M, Deng X.-Q, Gong G.-H, Wei C.-X, Quan Z.-S. J. Enzyme Inhib. Med. Chem. 2013; 28: 792
31 4-(4-Chlorobenzyl)-2-[4-(trifluoromethoxy)benzyl]phthalazin-1(2H)-one (3a): Typical Procedure A mixture of 4-(4-chlorobenzyl)phthalazin-1(2H)-one (1; 0.37 mmol, 1.0 equiv), 4-(trifluoromethoxy)benzyl bromide (2a; 0.5 mmol, 1.5 equiv), Cs₂CO₃ (0.74 mmol, 2.0 equiv), and KI (0.1 equiv) in MeCN (3 mL) was stirred at RT for 60–90 min in a laboratory ultrasonic bath (LABMAN Digital Ultrasonic Cleaner LMUC-6; 40 kHz ultrasound). The bath temperature was maintained by adding cold water from time to time when the temperature exceeded 28 °C. When the reaction was complete (TLC), the solvent was removed under a low vacuum and the solid residue was washed with H₂O. The product was extracted with CH₂Cl₂ and the extracts were dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The crude compound was purified by column chromatography (silica gel, EtOAc–hexane) to give a pale yellow solid; yield: 78%; mp 110–112 °C. IR (ATR): 2926, 2853, 1666, 1649, 1490, 1278, 1154, 1099, 1017, 749 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.52–8.28 (m, 1 H), 7.84–7.63 (m, 3 H), 7.50 (d, J = 8.5 Hz, 2 H), 7.25 (d, J = 9.2 Hz, 2 H), 7.16 (dd, J = 8.1, 2.8 Hz, 4 H), 5.39 (s, 2 H), 4.25 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 159.2, 148.8, 145.1, 136.1, 135.7, 133.1, 132.7, 131.4, 130.3 (2 C), 129.8 (2 C), 129.1, 128.8 (2 C), 128.4, 127.5, 124.9, 121.7, 121.0, 120.5 (q, J = 257.1 Hz), 53.8, 38.2. ¹⁹F NMR (377 MHz, CDCl₃): δ = –57.68. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₇ClF₃N₂O₂: 445.0931; found: 445.0932.

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