One-Pot Synthesis of N-Monosubstituted Ureas from Nitriles via Tiemann Rearrangement

Chien-Hong Wang; Tsung-Han Hsieh; Chia-Chi Lin; Wen-Hsiung Yeh; Chih-An Lin; Tun-Cheng Chien

doi:10.1055/s-0034-1381007

Synlett, Table of Contents

Synlett 2015; 26(13): 1823-1826
DOI: 10.1055/s-0034-1381007

letter

One-Pot Synthesis of N-Monosubstituted Ureas from Nitriles via Tiemann Rearrangement

Chien-Hong Wang

Department of Chemistry, National Taiwan Normal University, No.88, Sec.4, Ting-Zhou Road, Taipei 11677, Taiwan Email: tcchien@ntnu.edu.tw

,

Tsung-Han Hsieh

Department of Chemistry, National Taiwan Normal University, No.88, Sec.4, Ting-Zhou Road, Taipei 11677, Taiwan Email: tcchien@ntnu.edu.tw

,

Chia-Chi Lin

Department of Chemistry, National Taiwan Normal University, No.88, Sec.4, Ting-Zhou Road, Taipei 11677, Taiwan Email: tcchien@ntnu.edu.tw

,

Wen-Hsiung Yeh

Department of Chemistry, National Taiwan Normal University, No.88, Sec.4, Ting-Zhou Road, Taipei 11677, Taiwan Email: tcchien@ntnu.edu.tw

,

Chih-An Lin

Department of Chemistry, National Taiwan Normal University, No.88, Sec.4, Ting-Zhou Road, Taipei 11677, Taiwan Email: tcchien@ntnu.edu.tw

,

Tun-Cheng Chien*

Department of Chemistry, National Taiwan Normal University, No.88, Sec.4, Ting-Zhou Road, Taipei 11677, Taiwan Email: tcchien@ntnu.edu.tw

› Author Affiliations

Abstract

All articles of this category

Abstract

Amidoximes, obtained from the reaction of nitriles with hydroxylamine, underwent Tiemann rearrangement in the presence of benzenesulfonyl chlorides (TsCl or o-NsCl) to form the N-substituted cyanamides. Subsequently, acidic hydrolysis of the cyanamides afforded the corresponding N-monosubstituted ureas. The synthesis of N-monosubstituted ureas from nitriles was accomplished by three steps in one pot, which provides a direct access to versatile N-monosubstituted urea derivatives from a wide variety of nitriles.

Key words

urea - cyanamide - amidoxime - hydrolysis - Tiemann rearrangement

Full Text

References

References and Notes

1a Han S, Siegel DS, Morrison KC, Hergenrother PJ, Movassaghi M. J. Org. Chem. 2013; 78: 11970
1b Reyes JC. P, Romo D. Angew. Chem. Int. Ed. 2012; 51: 6870
1c Rogers EW, Molinski TF. J. Org. Chem. 2009; 74: 7660
1d Knott KE, Auschill S, Jaeger A, Knoelker H.-J. Chem. Commun. 2009; 1467
1e Rogers EW, Dalisay DS, Molinski TF. Angew. Chem. Int. Ed. 2008; 47: 8086
1f Jacquot DE. N, Zoellinger M, Lindel T. Angew. Chem. Int. Ed. 2005; 44: 2295
1g Hanessian S, Huang G, Chenel C, Machaalani R, Loiseleur O. J. Org. Chem. 2005; 70: 6721

2 McKay MJ, Nguyen HM. Carbohydr. Res. 2014; 385: 18

3a Heravi M, Asadi S, Lashkariani B. Mol. Diversity 2013; 17: 389
3b El Gihani MT, Heaney H. Synthesis 1998; 357

4a Hernández-Rodríguez M, Avila-Ortiz CG, del Campo JM, Hernández-Romero D, Rosales-Hoz MJ, Juaristi E. Aust. J. Chem. 2008; 61: 364
4b Connon SJ. Chem. Commun. 2008; 2499
4c Connon SJ. Chem. Eur. J. 2006; 12: 5418

5 Belfrage AK, Gising J, Svensson F, Åkerblom E, Sköld C, Sandström A. Eur. J. Org. Chem. 2015; 978
6 Gong H, Yang M, Xiao Z, Doweyko AM, Cunningham M, Wang J, Habte S, Holloway D, Burke C, Shuster D, Gao L, Carman J, Somerville JE, Nadler SG, Salter-Cid L, Barrish JC, Weinstein DS. Bioorg. Med. Chem. Lett. 2014; 24: 3268

7a Lin W.-H, Hsu JT. A, Hsieh S.-Y, Chen C.-T, Song J.-S, Yen S.-C, Hsu T, Lu C.-T, Chen C.-H, Chou L.-H, Yang Y.-N, Chiu C.-H, Chen C.-P, Tseng Y.-J, Yen K.-J, Yeh C.-F, Chao Y.-S, Yeh T.-K, Jiaang W.-T. Bioorg. Med. Chem. 2013; 21: 2856
7b Li H.-F, Lu T, Zhu T, Jiang Y.-J, Rao S.-S, Hu L.-Y, Xin B.-T, Chen Y.-D. Eur. J. Med. Chem. 2009; 44: 1240
7c Michaux C, Dogné J.-M, Rolin S, Masereel B, Wouters J, Durant F. Eur. J. Med. Chem. 2003; 38: 703

8 Tuerp D, Bruchmann B. Macromol. Rapid Commun. 2015; 36: 138

9a Wang L, Liu S, Li Z, Yu Y. Org. Lett. 2011; 13: 6137
9b Houlden CE, Hutchby M, Bailey CD, Ford JG, Tyler SN. G, Gagné MR, Lloyd-Jones GC, Booker-Milburn KI. Angew. Chem. Int. Ed. 2009; 48: 1830

10a Abdigali AB, Aleksandr YY, Sergei NV. Russ. Chem. Rev. 1998; 67: 295
10b Vishnyakova TP, Golubeva IA, Glebova EV. Russ. Chem. Rev. 1985; 54: 249
10c Kutepov DF. Russ. Chem. Rev. 1962; 31: 633

11a Sharma R, Samadhiya P, Srivastava SD, Srivastava SK. Helv. Chim. Acta 2012; 95: 514
11b Samadhiya P, Sharma R, Srivastava SK, Srivastava SD. Chin. J. Chem. 2011; 29: 1745
11c Hackl KA, Falk H. Monatsh. Chem. 1992; 123: 599

12 Curtis N. Aust. J. Chem. 1988; 41: 585
13 Breitler S, Oldenhuis NJ, Fors BP, Buchwald SL. Org. Lett. 2011; 13: 3262

14a Nandakumar MV. Tetrahedron Lett. 2004; 45: 1989
14b Sergeev AG, Artamkina GA, Beletskaya IP. Tetrahedron Lett. 2003; 44: 4719
14c Artamkina GA, Sergeev AG, Beletskaya IP. Russ. J. Org. Chem. 2002; 38: 538
14d Artamkina GA, Sergeev AG, Beletskaya IP. Tetrahedron Lett. 2001; 42: 4381

15a Dalby A, Mo X, Stoa R, Wroblewski N, Zhang Z, Hagen TJ. Tetrahedron Lett. 2013; 54: 2737
15b De Luca L, Porcheddu A, Giacomelli G, Murgia I. Synlett 2010; 2439
15c El-Deeb IM, Bayoumi SM, El-Sherbeny MA, Abdel-Aziz AA. M. Eur. J. Med. Chem. 2010; 45: 2516
15d Harriman GC, Brewer M, Bennett R, Kuhn C, Bazin M, Larosa G, Skerker P, Cochran N, Gallant D, Baxter D, Picarella D, Jaffee B, Luly JR, Briskin MJ. Bioorg. Med. Chem. Lett. 2008; 18: 2509

16a Nasrollahzadeh M, Azarian A, Ehsani A, Sajadi SM, Babaei F. Mater. Res. Bull. 2014; 55: 168
16b Mohy El Dine T, Chapron S, Duclos M.-C, Duguet N, Popowycz F, Lemaire M. Eur. J. Org. Chem. 2013; 5445
16c Manidhar DM, Uma Maheswara Rao K, Sures Reddy C, Syamasunder C, Adeppa K, Misra K. Res. Chem. Intermed. 2012; 38: 2479
16d Atkinson BN, Chhatwal AR, Lomax HV, Walton JW, Williams JM. J. Chem. Commun. 2012; 48: 11626
16e Verardo G, Bombardella E, Venneri CD, Strazzolini P. Eur. J. Org. Chem. 2009; 6239
16f Diss ML, Kennan AJ. Biopolymers 2007; 86: 276
16g Liu Q, Luedtke NW, Tor Y. Tetrahedron Lett. 2001; 42: 1445
16h Seyferth D, Dow AW, Menzel H, Flood TC. J. Am. Chem. Soc. 1968; 90: 1080

17a Ludek OR, Marquez VE. J. Org. Chem. 2012; 77: 815
17b Browne D, O’Brien M, Koos P, Cranwell PB, Polyzos A, Ley SV. Synlett 2012; 23: 1402
17c Boiocchi M, Fabbrizzi L, Garolfi M, Licchelli M, Mosca L, Zanini C. Chem. Eur. J. 2009; 15: 11288
17d Reisman SE, Ready JM, Weiss MM, Hasuoka A, Hirata M, Tamaki K, Ovaska TV, Smith CJ, Wood JL. J. Am. Chem. Soc. 2008; 130: 2087
17e Tao B, Timberlake JW. Synthesis 2000; 1449
17f Kobayashi T, Seki T, Ichimura K. Chem. Commun. 2000; 1193

18a Nasrollahzadeh M, Enayati M, Khalaj M. RSC Adv. 2014; 4: 26264
18b Nasrollahzadeh M. RSC Adv. 2014; 4: 29089
18c Sajadi SM, Maham M. J. Chem. Res. 2013; 623
18d Kim SH, Park BR, Kim JN. Bull. Korean Chem. Soc. 2011; 32: 716
18e Xiao ZL, Yang MG, Tebben AJ, Galella MA, Weinstein DS. Tetrahedron Lett. 2010; 51: 5843
18f Iio K, Ichikawa E. Bull. Chem. Soc. Jpn. 1984; 57: 2009

19a Tiemann F. Ber. Dtsch. Chem. Ges. 1891; 24: 4162
19b Pinnow J. Ber. Dtsch. Chem. Ges. 1891; 24: 4167

20 Partridge MW, Turner HA. J. Pharm. Pharmacol. 1953; 5: 103

21a Bakunov SA, Rukavishnikov AV, Tkachev AV. Synthesis 2000; 1148
21b Bakunov SA, Rukavishnikov AV, Tkachev AV. Synthesis 1994; 935

22 Ulrich H, Tucker B, Richter R. J. Org. Chem. 1978; 43: 1544

23a Richter R, Tucker B, Ulrich H. J. Org. Chem. 1983; 48: 1694
23b Damrauer R, Soucy D, Winkler P, Eby S. J. Org. Chem. 1980; 45: 1315
23c Dondoni A, Barbaro G, Battaglia A. J. Org. Chem. 1977; 42: 3372
23d Garapon J, Sillion B, Bonnier JM. Tetrahedron Lett. 1970; 11: 4905
23e Boyer JH, Frints PJ. A. J. Org. Chem. 1970; 35: 2449

24 Lin C.-C, Hsieh T.-H, Liao P.-Y, Liao Z.-Y, Chang C.-W, Shih Y.-C, Yeh W.-H, Chien T.-C. Org. Lett. 2014; 16: 892
25 General Procedure for the One-Pot Synthesis of N-Monosubstituted Urea 4 from Nitrile 1 (Scheme 3) To the solution of nitrile 1 in EtOH (0.1 M) was added 50 wt% aq hydroxylamine solution (1.2 equiv). The mixture was stirred at reflux temperature for 1.5 h. After cooling to r.t., the reaction mixture was concentrated under reduced pressure. The crude amidoxime product 2 was dissolved in CH₂Cl₂ (0.1 M), and ArSO₂Cl (TsCl or o-NsCl, 1.05 equiv) and DIPEA (1.05 equiv) were added at 0 °C. The mixture was stirred under nitrogen atmosphere at r.t. for 3 h or at reflux temperature for 1 h.²⁴ The mixture was concentrated under reduced pressure. The crude cyanamide product 3 was dissolved in the mixture of 1 N aq HCl solution and EtOH (0.1 M, 1 N HCl–EtOH = 1:4, v/v). The mixture was stirred at reflux temperature for 3 h under nitrogen. After cooling to r.t. the reaction mixture was concentrated under reduced pressure, and the residue was purified by flash column chromatography.
26 Analytical Data of Compounds 4e–k
N-(4-Nitrophenyl)urea (4e) Mp 213–215 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 9.29 (s, 1 H, NH), 8.11 (d, 2 H, J = 9.2 Hz), 7.62 (d, 2 H, J = 9.2 Hz), 6.20 (s, 2 H, NH₂). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 155.4, 147.3, 140.5, 125.1 (CH), 117.0 (CH). MS (EI, 20 eV): m/z = 108 (56), 138 (100), 181 (40) [M⁺]. ESI-MS: m/z = 167 (100), 182 (73) [M + 1]. HRMS (EI): m/z calcd for C₇H₇N₃O₃: 181.0487; found: 181.0486. N-(4-Trifluoromethylphenyl)urea (4f) Mp 144–145 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.95 (s, 1 H, NH), 7.60 (d, 2 H, J = 8.7 Hz), 7.54 (d, 2 H, J = 8.7 Hz), 6.04 (s, 2 H, NH₂). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 155.7, 144.3, 125.9 (q, J = 3.0 Hz, CH), 124.6 (q, J = 270.0 Hz, CF₃), 121.1 (q, J = 32.0 Hz), 117.4 (CH). MS (EI, 20 eV): m/z = 161 (100), 204 (41) [M⁺]. ESI-MS: m/z = 205 (100) [M + 1]. HRMS (EI): m/z calcd for C₈H₇F₃N₂O: 204.0510; found: 204.0508. N-(3-Methoxyphenyl)urea (4g) Mp 128–130 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.51 (s, 1 H, NH), 7.08–7.12 (m, 2 H), 6.87 (d, 1 H, J = 7.9 Hz), 6.47 (d, 1 H, J = 8.0 Hz), 5.81 (s, 2 H, NH₂), 3.69 (s, 3 H, CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 159.7, 156.0, 141.8, 129.4 (CH), 110.2 (CH), 106.5 (CH), 103.6 (CH), 54.9 (CH). ESI-MS: m/z = 167 [M + 1]. HRMS (EI): m/z calcd for C₈H₁₀N₂O₂: 166.0742; found: 166.0741. N-(2-Methylphenyl)urea (4h) Mp 194–196 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.77 (d, 1 H, J = 8.0 Hz), 7.66 (s, 1 H, NH), 7.12–7.06 (m, 2 H), 6.87 (t, 1 H, J = 7.3), 6.00 (s, 2 H, NH₂), 2.18 (s, 3 H, CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 156.1, 138.2, 130.0 (CH), 127.0 (CH), 126.0, 123.0 (CH), 120.9 (CH), 17.9 (CH₃). MS (EI, 20 eV): m/z = 107 (100), 150 (62) [M⁺]. HRMS (EI): m/z calcd for C₈H₁₀N₂O: 150.0793; found: 150.0792. N-(2-Chlorophenyl)urea (4i) Mp 190–192 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.12 (dd, 1 H, J = 8.4, 1.3 Hz), 8.03 (s, 1 H, NH), 7.38 (dd, 1 H, J = 8.3, 0.9 Hz), 7.24–7.20 (m, 1 H), 6.96–6.92 (m, 1 H), 6.37 (s, 2 H, NH₂). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 155.6, 136.7, 129.0, 127.4, 122.5, 121.4, 121.1. MS (EI, 20 eV): m/z = 127 (100), 129 (30), 135 (40), 170 (18) [M⁺], 172 (8) [M + 2]. HRMS (EI): m/z calcd for C₇H₇ClN₂O: 170.0247; found: 170.0246. 1,3-Dimethyl-5-ureidouracil (4j) Mp 254–258 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.09 (s, 1 H, NH), 7.84 (s, 1 H), 6.26 (s, 2 H, NH₂), 3.29 (s, 3 H, CH₃), 3.20 (s, 3 H, CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 160.2, 156.5, 149.8, 128.5, 115.0, 70.2, 37.1, 28.4. MS (EI, 20 eV): m/z = 70 (42), 155 (100), 198 (10) [M⁺]. HRMS (EI): m/z calcd for C₇H₁₀N₄O₃: 198.0753; found: 198.0760. 2-Chloro-3-ureidopyridine (4k) Mp 210–212 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.50 (dd, 1 H, J = 8.2, 1.5 Hz), 8.19 (s, 1 H, NH), 7.96 (dd, 1 H, J = 4.5, 1.5 Hz), 7.32 (dd, 1 H, J = 8.2, 4.6 Hz), 6.52 (s, 2 H, NH₂). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 155.4, 141.5 (CH), 138.5, 133.9, 128.3 (CH), 123.3 (CH). ESI-MS: m/z = 155 (28), 172 (100) [M + 1]. HRMS (EI): m/z calcd for C₆H₆ClN₃O: 171.0199; found: 171.0201.

Supplementary Material

Supporting Information