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Synlett 2020; 31(07): 703-707
DOI: 10.1055/s-0039-1691583
DOI: 10.1055/s-0039-1691583
letter
Ultrasound-Assisted Synthesis of N-Acylcyanamides and N-Acyl-Substituted Imidazolones from Carboxylic Acids by Using Trichloroisocyanuric Acid/Triphenylphosphine
This research work was partially supported by Chiang Mai University. Financial support from The Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program to D.Y. (Grant No. PHD/0023/2559) and the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Office of the Higher Education Commission, Ministry of Education, Thailand are also gratefully acknowledged.Further Information
Publication History
Received: 11 December 2019
Accepted after revision: 07 January 2020
Publication Date:
28 January 2020 (online)
![](https://www.thieme-connect.de/media/synlett/202007/lookinside/thumbnails/st-2019-d0667-l_10-1055_s-0039-1691583-1.jpg)
Abstract
A convenient ultrasound-assisted one-pot synthesis of N-acylcyanamides starting from readily available carboxylic acids and sodium cyanamide has been developed. Upon activation in the presence of trichloroisocyanuric acid (TCCA) and triphenylphosphine, a range of carboxylic acids was converted into N-acylcyanamides in good to excellent yields within 10 minutes at room temperature without base. Remarkably, N-acyl-substituted imidazolones were readily accessible through guanylation-cyclization of the in situ generated N-acylcyanamides.
Key words
acylation - cyclization - ultrasound - trichloroisocyanuric acid - N-cyanocarboxamides - imidazolonesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691583.
- Supporting Information
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References and Notes
- 1 Maguire JH, McKee RL. J. Org. Chem. 1974; 39: 3434
- 2 Shestakov AS, Gusakova NV, Shikhaliev KS, Zagoruiko AV. Russ. J. Gen. Chem. 2006; 76: 1647
- 3a Vieira E, Huwyler J, Jolidon S, Knoflach F, Mutel V, Wichmann J. Bioorg. Med. Chem. Lett. 2005; 15: 4628
- 3b Ziedan NI, Stefanelli F, Fogli S, Westwell AD. Eur. J. Med. Chem. 2010; 45: 4523
- 4 Salvant JM, Edwards AV, Kurek DZ, Looper RE. J. Org. Chem. 2017; 82: 6958
- 5 Shestakov AS, Gusakova NV, Shikhaliev KS, Timoshkina AG. Russ. J. Org. Chem. 2007; 43: 1825
- 6a Servais A, Azzouz M, Lopes D, Courillon C, Malacria M. Angew. Chem. Int. Ed. 2007; 46: 576
- 6b Larraufie M.-H, Malacria M, Courillon C, Ollivier C, Fensterbank L, Lacote E. Tetrahedron 2013; 69: 7699
- 6c Larraufie M.-H, Courillon C, Ollivier C, Lacote E, Malacria M, Fensterbank L. J. Am. Chem. Soc. 2010; 132: 4381
- 6d Zheng J, Zhang Y, Wang D, Cui S. Org. Lett. 2016; 18: 1768
- 7 Larraufie M.-H, Ollivier C, Fensterbank L, Malacria M, Lacote E. Angew. Chem. Int. Ed. 2010; 49: 2178
- 8 Maestri G, Larraufie M.-H, Ollivier C, Malacria M, Fensterbank L, Lacote E. Org. Lett. 2012; 14: 5538
- 9a Yokoo K, Yamawaki K, Yoshida Y, Yonezawa S, Yamano Y, Tsuji M, Hori T, Nakamura R, Ishikura K. Eur. J. Med. Chem. 2016; 124: 698
- 9b Yang W.-C, Li J, Li J, Chen Q, Yang G.-F. Bioorg. Med. Chem. Lett. 2012; 22: 1455
- 9c Bergstroem CA. S, Bolin S, Artursson P, Roenn R, Sandstroem A. Eur. J. Pharm. Sci. 2009; 38: 556
- 9d Nurbo J, Peterson SD, Dahl G, Danielson UH, Karlen A, Sandstroem A. Bioorg. Med. Chem. 2008; 16: 5590
- 9e Roenn R, Gossas T, Sabnis YA, Daoud H, Aakerblom E, Danielson UH, Sandstroem A. Bioorg. Med. Chem. 2007; 15: 4057
- 10a Goetz N, Zeeh B. Synthesis 1976; 268
- 10b Anatol J, Berecoechea J. Synthesis 1975; 111
- 10c Howard JC, Youngblood FE. J. Org. Chem. 1966; 31: 959
- 10d Vesci L, Milazzo FM, Stasi MA, Pace S, Manera F, Tallarico C, Cini E, Petricci E, Manetti F, De Santis R, Giannini G. Eur. J. Med. Chem. 2018; 157: 368
- 11 Krishnaiah M, Rodrigues de Almeida N, Udumula V, Song Z, Chhonker YS, Abdelmoaty MM, Aragao do Nascimento V, Murry DJ, Conda-Sheridan M. Eur. J. Med. Chem. 2018; 143: 936
- 12 Wong FF, Chen C.-Y, Yeh M.-Y. Synlett 2006; 559
- 13 Chen C.-Y, Wong FF, Huang J.-J, Lin S.-K, Yeh M.-Y. Tetrahedron Lett. 2008; 49: 6505
- 14a Aakerbladh L, Odell LR. J. Org. Chem. 2016; 81: 2966
- 14b Aakerbladh L, Schembri LS, Larhed M, Odell LR. J. Org. Chem. 2017; 82: 12520
- 14c Mane RS, Nordeman P, Odell LR, Larhed M. Tetrahedron Lett. 2013; 54: 6912
- 14d Wu X.-F, Oschatz S, Sharif M, Beller M, Langer P. Tetrahedron 2014; 70: 23
- 14e Nordeman P, Chow SY, Odell AF, Antoni G, Odell LR. Org. Biomol. Chem. 2017; 15: 4875
- 15a Banerjee B. Ultrason. Sonochem. 2017; 35: 1
- 15b Kaur N. Mini-Rev. Org. Chem. 2019; 16: 481
- 15c Mandal B. ChemistrySelect 2019; 4: 8301
- 16 Mason TJ. Chem. Soc. Rev. 1997; 26: 443
- 17a Kolvari E, Ghorbani-Choghamarani A, Salehi P, Shirini F, Zolfigol MA. J. Iran. Chem. Soc. 2007; 4: 126
- 17b Gaspa S, Carraro M, Pisano L, Porcheddu A, De Luca L. Eur. J. Org. Chem. 2019; 3544
- 18 Rodrigues R. dC, Barros IM. A, Lima EL. S. Tetrahedron Lett. 2005; 46: 5945
- 19 Singh M, Singh AS, Mishra N, Agrahari AK, Tiwari VK. Synthesis 2019; 51: 2183
- 20 Akhlaghinia B, Rouhi-Saadabad H. Can. J. Chem. 2013; 91: 181
- 21 Entezari N, Akhlaghinia B, Rouhi-Saadabad H. Croat. Chem. Acta 2014; 87: 201
- 22 Synthesis of N-Acylcyanamides 2; General Procedure To a cold solution of triphenylphosphine (0.201 g, 0.768 mmol) in CH2Cl2 (2 mL) was added trichloroisocyanuric acid (0.0595 g, 0.256 mmol) with continuous sonication for 5 min. The requisite carboxylic acid (0.64 mmol) was then added, and sonication was continued for 5 min. The temperature was raised to r.t. before adding an aqueous solution of sodium cyanamide (0.050 g, 0.768 mmol, 1 mL). After sonication for 10 min, the crude mixture was quenched with 1 M HCl, then extracted with EtOAc (3 × 10 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was then purified by short column chromatography by using 10% MeOH/EtOAc as the eluent. N-Cyanobenzo[b]thiophene-2-carboxamide (2s) White solid; yield: 0.1139g (88%); mp 165–167 °C; Rf 0.28(20% MeOH/EtOAc). 1H NMR (400 MHz, DMSO-d6 ): δ = 12.09 (s, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.39 (s, 1 H), 7.30 (t, J = 8.0 Hz, 1 H), 7.11 (t, J = 8.0 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6 ): δ = 161.0, 138.4, 127.7, 127.1, 125.9, 123.0, 121.1, 113.1, 109.2, 107.9.
- 23 Xiao Z, Yang MG, Tebben AJ, Galella MA, Weinstein DS. Tetrahedron Lett. 2010; 51: 5843
- 24a Bahl A, Joshi P, Bharate SB, Chopra H. Med. Chem. Res. 2014; 23: 1925
- 24b Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B, Ogawa Y, Hagiwara M, Eisenreich A, Rauch U, Knapp S, Meijer L, Bazureau J.-P. J. Med. Chem. 2011; 54: 4172
- 24c Norman BH, Fisher MJ, Schiffler MA, Kuklish SL, Hughes NE, Czeskis BA, Cassidy KC, Abraham TL, Alberts JJ, Luffer-Atlas D. J. Med. Chem. 2018; 61: 2041
- 24d Ombrato R, Cazzolla N, Mancini F, Mangano G. J. Chem. Inf. Model. 2015; 55: 2540
- 25 Synthesis of N-Acyl-Substituted Imidazolones 3; General Procedure Following the above described procedure for the synthesis of compound 2 using the requisite carboxylic acid (0.64 mmol), after complete formation of 2 as detected by TLC, the crude reaction was concentrated under reduced pressure before adding DMF (1 mL). The mixture was then transferred into a 10 mL pressure tube, followed by addition of the amino acid methyl ester hydrochloride (0.768 mmol) and NEt3 (0.27 mL, 1.92 mmol). The pressure tube was then placed in a preset oil bath at 130 °C and the reaction mixture was stirred for 30–40 min. The mixture was then quenched with H2O and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography by using 30–50% EtOAc/hexanes as the eluent. N-(1-Oxo-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazol-3-yl)benzamide (3ae) Colorless oil; yield: 0.1198g (77%); Rf 0.40(40% EtOAc/hexane). 1H NMR (500 MHz, CDCl3): δ = 10.76 (s, 1 H), 8.27 (d, J = 7.5 Hz, 2 H), 7.52 (t, J = 7.5 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 2 H), 4.14 (t, J = 9.0 Hz, 1 H), 3.95 (q, J = 9.0 Hz, 1 H), 3.47 (t, J = 9.0 Hz, 1 H), 2.34–2.11 (m, 3 H), 1.78 (quin, J = 9.0 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 177.8, 173.9, 162.0, 136.4, 132.5, 129.9, 128.1, 62.3, 46.6, 27.1, 27.0. TOF-HRMS: m/z [M + H]+ calcd for C13H14N3O2: 244.1086; found: 244.1081.
- 26 Denton RM, An J, Adeniran B, Blake AJ, Lewis W, Poulton AM. J. Org. Chem. 2011; 76: 6749
- 27 Sugimoto O, Tanji K.-i. Heterocycles 2005; 65: 181