Efficient S-Acylation of Thiourea

David J. Jones; Uday B. Rao Khandavilli; Eileen M. O’Leary; Simon E. Lawrence; Timothy P. O’Sullivan

doi:10.1055/s-0037-1610370

SynOpen, Inhaltsverzeichnis

CC BY ND NC 4.0 · SynOpen 2018; 02(04): 0263-0267
DOI: 10.1055/s-0037-1610370

letter

Copyright with the author

Efficient S-Acylation of Thiourea

David J. Jones

^aSchool of Chemistry, University College Cork, Cork, Ireland eMail: tim.osullivan@ucc.ie

^bAnalytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland

^eSynthesis and Solid-State Pharmaceutical Centre, University College Cork, Cork, Ireland

,

Uday B. Rao Khandavilli

^aSchool of Chemistry, University College Cork, Cork, Ireland eMail: tim.osullivan@ucc.ie

^bAnalytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland

,

Eileen M. O’Leary

^cDepartment of Physical Sciences, Cork Institute of Technology, Cork, Ireland

,

Simon E. Lawrence

^aSchool of Chemistry, University College Cork, Cork, Ireland eMail: tim.osullivan@ucc.ie

^bAnalytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland

^eSynthesis and Solid-State Pharmaceutical Centre, University College Cork, Cork, Ireland

,

Timothy P. O’Sullivan *

^aSchool of Chemistry, University College Cork, Cork, Ireland eMail: tim.osullivan@ucc.ie

^bAnalytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland

^dSchool of Pharmacy, University College Cork, Cork, Ireland

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Abstract

Efficient S-acylation of thiourea using a variety of acid chlorides is reported. Structurally diverse aryl and alkyl substrates are compatible with this methodology. Confirmation that acylation occurs exclusively on the sulfur atom of thiourea is provided by single-crystal X-ray crystallographic analysis.

Key words

isothiourea - thiourea - organosulfur - sulfur transfer

Volltext

Referenzen

References and Notes

1a Krishnamurthy M, Basavaprabhu, Sharanabai KM, Sureshbabu VV. Tetrahedron Lett. 2014; 55: 5609
1b Kim H.-Y, Kwak SH, Lee G.-H, Gong Y.-D. Tetrahedron 2014; 70: 8737
1c Alcolea V, Garnica P, Palop J, Sanmartín C, González-Peñas E, Durán A, Lizarraga E. Molecules 2017; 22: 1314
1d Friebe M, Mahmood A, Spies H, Berger R, Johannsen B, Mohammed A, Eisenhut M, Bolzati C, Davison A, Jones AG. J. Med. Chem. 2000; 43: 2745
1e Wu Y.-J, Guernon J, Park H, Thompson LA. J. Org. Chem. 2016; 81: 3386

2a Hickey SM, White JM, Pfeffer FM, Ashton TD. Synlett 2015; 26: 1759
2b Takaya J, Mio K, Shiraishi T, Kurokawa T, Otsuka S, Mori Y, Uesugi M. J. Am. Chem. Soc. 2015; 137: 15859
2c Xu Z, Guo J, Yang Y, Zhang M, Ba M, Li Z, Cao Y, He R, Yu M, Zhou H, Li X, Huang X, Guo Y, Guo C. Eur. J. Med. Chem. 2016; 123: 309

3a Palanki MS. S, Erdman PE, Manning AM, Ow A, Ransone LJ, Spooner C, Suto C, Suto M. Bioorg. Med. Chem. Lett. 2000; 10: 1645
3b Zanatta N, Fortes AS, Bencke CE, Marangoni MA, Camargo AF, Fantinel CA, Bonacorso HG, Martins MA. P. Synthesis 2015; 47: 827
3c Kaur H, Balzarini J, de Kock C, Smith PJ, Chibale K, Singh K. Eur. J. Med. Chem. 2015; 101: 52
3d Murai K, Miyazaki S, Fujioka H. Tetrahedron Lett. 2012; 53: 3746

4a Liu C, Guo W, Shi X, Kaium MA, Gu X, Zhu YZ. Eur. J. Med. Chem. 2011; 46: 3996
4b Qiu K, Wang R. Synthesis 2015; 47: 3186
4c Yang Z, Zheng Y, Xu J. Synlett 2013; 24: 2165

5a Fujisaki S, Fujiwara I, Norisue Y, Kajigaeshi S. Bull. Chem. Soc. Jpn. 1985; 58: 2429
5b Murphy Kessabi F, Beaudegnies R, Quaranta L, Lamberth C. Tetrahedron Lett. 2016; 57: 5511
5c Floyd N, Vijayakrishnan B, Koeppe JR, Davis BG. Angew. Chem. Int. Ed. 2009; 48: 7798
5d Brown TJ, Chapman RF, Cook DC, Hart TW, McLay IM, Jordan R, Mason JS, Palfreyman MN, Walsh RJ. A. J. Med. Chem. 1992; 35: 3613
5e Minard TA, Oswin CT, Waldie FD. C, Howell JK, Scott BM. T, Mondo DD, Sullivan RJ, Stein B, Jennings M, Schlaf M. J. Mol. Catal. A: Chem. 2016; 422: 175
5f Zong J, Mague JT, Pascal JrR. A. Tetrahedron 2017; 73: 455
5g Rotili D, De Luca A, Tarantino D, Pezzola S, Forgione M, Morozzo della Rocca B, Falconi M, Mai A, Caccuri AM. Eur. J. Med. Chem. 2015; 89: 156

6a Su X, Pradaux-Caggiano F, Vicker N, Thomas MP, Halem H, Culler MD, Potter BV. L. ChemMedChem 2011; 6: 1616
6b Marciniec K, Pawełczak B, Latocha M, Skrzypek L, Maciążek-Jurczyk M, Boryczka S. Molecules 2017; 22: 300
6c Lee YS, Kim HY, Kim Y, Seo JH, Roh EJ, Han H, Shin KJ. Bioorg. Med. Chem. 2012; 20: 4921

7a Emerson DW, Bennett BL, Steinberg SM. Synth. Commun. 2005; 35: 631
7b Chukicheva IY, Sukrusheva OV, Shumova OA, Mazaletskaya LI, Shevchenko OG, Kuchin AV. Russ. J. Gen. Chem. 2016; 86: 2052
7c Younai A, Fettinger JC, Shaw JT. Tetrahedron 2012; 68: 4320

8 Aoyagi N, Furusho Y, Endo T. Synlett 2014; 25: 983

9a Jones DJ, O’Leary EM, O’Sullivan TP. Tetrahedron Lett. 2017; 58: 4212
9b Raz R, Rademann J. Org. Lett. 2011; 13: 1606

10a Najda-Mocarska E, Zakaszewska A, Janikowska K, Makowiec S. Synth. Commun. 2018; 48: 14
10b Supady A, Hecht S, Baldauf C. Org. Lett. 2017; 19: 4199
10c Serdyuk OV, Heckel CM, Tsogoeva SB. Org. Biomol. Chem. 2013; 11: 7051
10d Fang X, Wang C.-J. Chem. Commun. 2015; 1185
10e Lippert KM, Hof K, Gerbig D, Ley D, Hausmann H, Guenther S, Schreiner PR. Eur. J. Org. Chem. 2012; 5919

11 Váňa J, Sedlák M, Padělková Z, Hanusek J. Tetrahedron 2012; 68: 9808
12 Kammel R, Tarabová D, Brož B, Hladíková V, Hanusek J. Tetrahedron 2017; 73: 1861
13 Kammel R, Hanusek J. Heterocycles 2014; 89: 1183

14a Southan GJ, Szabo C. Biochem. Pharmacol. 1996; 51: 383
14b Southan GJ, Zingarelli B, O’Connor M, Salzman AL, Szabo C. Br. J. Pharmacol. 1996; 117: 619
14c Southan GJ, Szabo C, Thiemermann C. Br. J. Pharmacol. 1995; 114: 510
14d Jang D, Szabo C, Murrell GA. Eur. J. Pharmacol. 1996; 312: 341

15a Mostert S, Mentz W, Petzer A, Bergh JJ, Petzer JP. Bioorg. Med. Chem. 2012; 20: 7040
15b Booysen HP, Moraal C, Terre’Blanche G, Petzer A, Bergh JJ, Petzer JP. Bioorg. Med. Chem. 2011; 19: 7507

16 Ganellin CR, Hosseini SK, Khalaf YS, Tertiuk W, Arrang JM, Garbarg M, Ligneau X, Schwartz JC. J. Med. Chem. 1995; 38: 3342

17a Nicholson A, Perry JD, James AL, Stanforth SP, Carnell S, Wilkinson K, Anjam Khan CM, De Soyza A, Gould FK. Int. J. Antimicrob. Agents 2012; 39: 27
17b Barker CA, Allison SE, Zlitni S, Nguyen ND, Das R, Melacini G, Capretta AA, Brown ED. Bioorg. Med. Chem. Lett. 2013; 23: 2426

18a Bonez PC, Rossi GG, Bandeira JR, Ramos AP, Mizdal CR, Agertt VA, Dalla Nora ES. S, de Souza ME, dos Santos Alves CF, dos Santos FS, Gündel A, de Almeida Vaucher R, Santos RC. V, de Campos MM. A. Microb. Pathog. 2017; 111: (Supplement C) 6
18b Bonez PC, Ramos AP, Nascimento K, Copetti PM, Souza ME, Rossi GG, Agertt VA, Sagrillo MR, Santos RC. V, Campos MM. A. Microb. Pathog. 2016; 99: (Supplement C) 14

19 Matsuno K, Takai K, Isaka Y, Unno Y, Sato M, Takikawa O, Asai A. Bioorg. Med. Chem. Lett. 2010; 20: 5126
20 Ferreira M, Assunção LS, Silva AH, Filippin-Monteiro FB, Creczynski-Pasa TB, Sá MM. Eur. J. Med. Chem. 2017; 129: (Supplement C) 151

21a Jamaleddini A, Mohammadizadeh MR. Tetrahedron Lett. 2017; 58: 78-81
21b Ingham RJ, Riva E, Nikbin N, Baxendale IR, Ley SV. Org. Lett. 2012; 14: 3920
21c Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu J, Zhao K, Shultz MD, Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang J, Zhang C, Li L, Zeng J, Feng L, Zhang C, Liu Y, Zhang M, Zhang L, Zhao M, Gao Z, Liu X, Fang D, Guo H, Mi Y, Gabriel T, Dillon MP, Atadja P, Oyang C. J. Med. Chem. 2017; 60: 2215
21d Geies AA, Abdel MoneamM. I, Kamal El-DeanA. M, Zaki RM, Abd El-NaeemE. E. J. Heterocycl. Chem. 2017; 54: 2012
21e Mousdis GA, Ganotopoulos N.-M, Barkaoui H, Abid Y, Psycharis V, Savvidou A, Raptopoulou CP. Eur. J. Inorg. Chem. 2017; 3401
21f Elacqua E, Manning KB, Lye DS, Pomarico SK, Morgia F, Weck M. J. Am. Chem. Soc. 2017; 139: 12240
21g Abul-Futouh H, Almazahreh LR, Harb MK, Görls H, El-khateeb M, Weigand W. Inorg. Chem. 2017; 56: 10437
21h Manos-Turvey A, Al-Ashtal HA, Needham PG, Hartline CB, Prichard MN, Wipf P, Brodsky JL. Bioorg. Med. Chem. Lett. 2016; 26: 5087
21i Tong S, Zhang M, Wang S, Yin R, Yu R, Wan S, Jiang T, Zhang L. Eur. J. Med. Chem. 2016; 123: (Supplement C) 849

22a Dixon AE, Hawthorne J. J. Chem. Soc., Trans. 1907; 91: 122
22b Dixon AE, Taylor J. J. Chem. Soc., Trans. 1920; 117: 720

23 Hemalatha P, Veeravazhuthi V. Acta Crystallogr., Sect. E: Struct. Rep. Online . 2008, 64; , 1805. CCDC Deposition Number: 695520
24 Biancalana L, Batchelor LK, De Palo A, Zacchini S, Pampaloni G, Dyson PJ, Marchetti F. Dalton Trans. 2017; 12001
25 General Procedure: To a stirred solution of thiourea (78 mg, 1.00 mmol, 1.00 equiv) in acetonitrile (10 mL) at 50 °C was added a solution of the required acid chloride (1.00 mmol, 1.00 equiv) in acetonitrile (10 mL) dropwise. The resulting thick suspension was allowed to stir at this temperature for a further one hour to ensure complete reaction. After one hour, the reaction mixture was cooled on ice and then vacuum filtered. The cake was washed with ethyl acetate (2 × 10 mL) to afford the products. The products were obtained quantitatively unless otherwise stated.Representative Examples: S-(3-Methoxybenzoyl)isothiouronium Chloride (5)Mp 166–168 °C (MeCN). ¹H NMR (400 MHz, DMSO-d ₆): δ = 3.80 (s, 3 H, OCH₃ ), 7.19 (dd, J = 8.15, 1.83 Hz, 1 H, ArC(2)H), 7.39–7.44 (m, 2 H, overlapping ArC(6)H and ArC(3)H), 7.53 (d, J = 8.15 Hz, 1 H, ArC(4)H), 9.62 (bs, 4 H, NH ₂=C-NH ₂). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 55.2, 113.8, 118.9, 121.5, 129.7, 132.1, 159.2, 167.1. IR (KBr): 3329, 3281, 3163, 3085, 2954, 2836, 1697, 1609, 1583, 1526, 1470, 1420, 1311, 1293, 1267, 1051, 755 cm^–1. HRMS (ESI⁺): m/z calcd. for C₉H₁₁N₂O₂S⁺: 211.0536; found: 211.0528. Anal. Calcd. for C₉H₁₁N₂O₂ClS: C, 44.00; H, 4.10; N, 11.40; Found: C, 44.31; H, 4.18; N, 11.71. S-(Decanoyl)isothiouronium Chloride (14)Mp 115–117 °C (MeCN).¹H NMR (400 MHz, DMSO-d ₆): δ = 0.86 (t, J = 7.51 Hz, 3 H, CH ₃(10)), 1.24 (m, 12 H, CH ₂(9-4)), 1.46–1.50 (m, 2 H, CH ₂(3)), 2.18 (t, J = 7.88 Hz, 2 H, CH ₂(2)), 9.18 (bs, 4 H, NH ₂=C-NH ₂). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.9, 22.1, 24.5, 28.5, 28.6, 28.7, 31.2, 33.6, 174.5. IR (KBr): 3385, 3261, 3175, 3031, 2822, 2859, 1748, 1676, 1427, 732 cm^–1. HRMS (ESI⁺): m/z calcd for C₁₁H₂₃N₂OS: 231.1531; Found: 231.1536. Anal. Calcd for C₁₁H₂₃N₂OClS: C, 49.52; H, 8.69; N, 10.50; Found: C, 49.18; H, 8.75; N, 10.71.Indomethacin Analogue 21Mp 168–171 °C (MeCN).¹H NMR (400 MHz, DMSO-d ₆): δ = 2.22 (s, 3 H, ArCH ₃), 3.67 (s, 2 H, CH ₂), 3.76 (s, 3 H, OCH ₃), 6.72 (dd, J = 8.18, 1.33 Hz, 1 H, C(6)H), 6.92 (d, J = 8.18 Hz, 1 H, C(7)H), 7.05 (d, J = 1.33 Hz, 1 H, C(4)H). 7.64–7.70 (m, 4 H, Ar(2′, 3′, 5′ and 6′)H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 13.2, 29.5, 55.4, 101.7, 111.3, 113.4, 114.6, 116.5, 129.0, 130.2, 130.71, 131.1, 134.1, 135.1, 137.6, 155.5, 167.8, 172.0. IR (KBr): 3332, 3312, 2952, 1727, 1687, 1657, 1482, 1308, 1227, 1047, 792 cm^–1. HRMS (ESI⁺): m/z calcd for C₂₀H₁₉ClN₃O₃S⁺: 416.0830; Found: 416.0851. Anal. Calcd for C₂₀H₁₉Cl₂N₃O₃S: C, 53.10; H, 4.23; N, 9.29; Found: C, 53.33; H 4.29; N, 9.45

Zusatzmaterial

Supporting Information