Convenient One-Pot Two-Step Synthesis of Symmetrical and Unsymmetrical Diacyl Ureas, Acyl Urea/Carbamate/Thiocarbamate Derivatives, and Related Compounds

Dedicated to Professor Richard J. Whitby

Abstract

A wide range of chemicals such as amides, hydrazides, amines, alcohols, carbazate, and sulfonate were reacted with acyl isocyanates generated by the reaction of primary amides with oxalyl chloride to give symmetrical and unsymmetrical diacyl urea derivatives, acyl ureas/carbamates/thiocarbamates, and related compounds. This method provides means for convenient one-pot, two-step synthesis of compounds bearing urea, carbamate, and other functional groups from cheap and commercially available starting reagents. It is expected that the results presented in this report will expand the medicinal chemist’s toolbox.

Key words

bioisostere - acyl isocyanates - symmetrical/unsymmetrical diacyl ureas - acyl ureas - acyl carbamates - acyl thiocarbamates

• References

• 1 Current address: University of South Carolina, S. o. M. G., Greenville, SC 29605, USA.
• 2 Current address: Marshall B. Ketchum University, C. o. P., Department of Pharmaceutical Sciences, 2575 Yorba Linda Blvd., Fullerton, CA 82831, USA. Phone: [phone]; [e-mail].
• 3 Patani GA, LaVoie EJ. Chem. Rev. 1996; 96: 3147
• 4 Silverman RB, Holladay MW. The Organic Chemistry of Drug Design and Drug Action . Academic Press; San Diego: 2014: 62
• 5 Ghosh AK, Brindisi M. J. Med. Chem. 2015; 58: 2895
• 6 Simplício AL, Clancy JM, Gilmer JF. Molecules 2008; 13: 519
• 7 Blum JL. Oncologist 2001; 6: 56
• 8 Tymoczko JL, Berg JM, Stryer L. Biochemistry: A Short Course . W. H. Freeman and Company; New York: 2015: 526
• 9 Bogolubsky AV, Moroz YS, Mykhailiuk PK, Granat DS, Pipko SE, Konovets AI, Doroschuk R, Tolmachev A. ACS Comb. Sci. 2014; 16: 303
• 10 Roche VF In Foye’s Principles of Medicinal Chemistry . Lemke TL, Williams DA, Roche VF, Zito SW. Walters Kluwer Health/Lippincott Williams & Wilkins; Baltimore: 2013: 1243
• 11a Ishikawa S, Mochizuki M. Genes Environ. 2007; 29: 1
• 11b Roche VF In Foye’s Principles of Medicinal Chemistry . Lemke TL, Williams DA, Roche VF, Zito SW. Walters Kluwer Health/Lippincott Williams & Wilkins; Baltimore: 2013: 1215
• 12 Harvison PJ, Rankin GO In Foye’s Principles of Medicinal Chemistry . Lemke TL, Williams DA, Roche VF, Zito SW. Walters Kluwer Health/Lippincott Williams & Wilkins; Baltimore: 2013: 740
• 13 Gallagher BB In Anticonvulsants . Vida J. Academic Press; New York: 1977: 42
• 14 Saam E. US Patent 914518A, 1909
• 15a Diflubenzuron. WHO Specifications and Evaluations for Public Health Pesticides; 2006; http://www.who.int/whopes/ quality/diflubenzuron_eval_march_2006.pdf.
• 15b Pete UD, Zade CM, Bhosale JD, Tupe SG, Chaudhary PM, Dikundwar AG, Bendre RS. Bioorg. Med. Chem. Lett. 2012; 22: 5550
• 16 Lufenuron. FAO Specifications and Evaluations for Agricultural Pesticides; 2008; http://www.fao.org/fileadmin/templates/ agphome/documents/Pests_Pesticides/Specs/Lufenuron08.pdf.
• 17 Woster PM In Foye’s Principles of Medicinal Chemistry . Lemke TL, Williams DA, Roche VF, Zito SW. Walters Kluwer Health/Lippincott Williams & Wilkins; Baltimore: 2013: 1298
• 18a Babad H, Zeiler AG. Chem. Rev. 1973; 73: 75
• 18b Bigi F, Maggia R, Sartori G. Green Chem. 2000; 2: 140
• 18c Kreye O, Mutlua H, Meier MA. R. Green Chem. 2013; 15: 1431
• 19a Dubé P, Nathel NF, Vetelino M, Couturier M, Aboussafy CL, Pichette S, Jorgensen ML, Hardink M. Org. Lett. 2009; 11: 5622
• 19b El Dine TM, Chapron S, Duclos M.-C, Duguet N, Popowycz F, Lemaire M. Eur. J. Org. Chem. 2013; 5445
• 20a Zadeh EH. G, Abo-Dya NE, Sotuyo AC, Ghiviriga I, Hall CD. Tetrahedron Lett. 2013; 54: 5467
• 20b Spyropoulos C, Kokotos CG. J. Org. Chem. 2014; 79: 4477
• 20c Han C, Porco JA. Jr. Org. Lett. 2007; 9: 1517
• 21a Yoshida M, Hara N, Okuyama S. Chem. Commun. 2000; 151
• 21b Kim SH, Hong SH. Org. Lett. 2016; 18: 212
• 21c Sun D.-L, Ye J.-H, Fang Y.-X, Chao Z.-S. Ind. Eng. Chem. Res. 2016; 55: 64
• 21d Shi F, Deng Y, SiMa T, Peng J, Gu Y, Qiao B. Angew. Chem. Int. Ed. 2003; 42: 3257
• 21e Díaz DJ, Darko AK, McElwee-White L. Eur. J. Org. Chem. 2007; 4453
• 22 Wu C, Cheng H, Liu R, Wang Q, Hao Y, Yua Y, Zhao F. Green Chem. 2010; 12: 1811
• 23a Schmidt E. J. Prakt. Chem. 1872; 5: 63
• 23b Stoughton RW, Diacylureas I. J. Org. Chem. 1938; 2: 514
• 24a Scholl R. Ber. Dtsch. Chem. Ges. 1890; 23: 3516
• 24b Meyer V, Jacobson P. Lehrbuch der Organischen Chemie: Allgemeiner Theil . Veit & Comp; Leipzig: 1893: 1013-1014
• 24c Bayer & Co. German Patent 286 760, 1913 ; Chem. Abstr. 1916, 10, 1579
• 25 Bornwater JT. Rec. Trav. Chim. Pays-Bas 1912; 31: 105
• 26a Speziale AJ, Smith LR. J. Org. Chem. 1962; 27: 3742
• 26b Speziale AJ, Smith LR, Fedder JE. J. Org. Chem. 1965; 30: 4306
• 26c Speziale AJ, Smith LR. US Patent 3213135, 1965
• 26d Speziale AJ, Smith LR. Org. Synth. 1966; 46: 16
• 26e Speziale AJ, Smith LR. J. Org. Chem. 1963; 28: 1805
• 26f Speziale AJ, Smith LR, Fedder JE. J. Org. Chem. 1965; 30: 4303
• 26g Smith LR, Speziale AJ, Fedder JE. J. Org. Chem. 1969; 34: 633
• 27 Wolfe JF, Trimitsis GB. Can. J. Chem. 1969; 47: 2097
• 28 Kanji Kubo K, Moriy A. Chem. Lett. 2005; 34: 1250
• 29 Chawla HM, Pathak M. Tetrahedron 1990; 46: 1331
• 30 Dean FW. US Patent 6448440 B1, 2004
• 31 Bjerglund K, Lindhardt AT, Skrydstrup T. J. Org. Chem. 2012; 77: 3793
• 32 Cohen VI. J. Org. Chem. 1974; 39: 3043
• 33 Basyouni MN, El-Khamry A.-M. Bull. Chem. Soc. Jpn. 1979; 52: 3728
• 34 Otohiko T, Tadashi I, Masashi T. Tetrahedron 1968; 24: 2583
• 35a Hoggarth E. J. Chem. Soc. 1949; 1160
• 35b Durant GJ. J. Chem. Soc. C 1967; 92
• 36a Nenitzescu CD, Necsoiu I, Zalman M. Comun. Acad. Rep. Populare Romine 1958; 8: 659 ; Chem. Abstr. 1959, 53, 17092
• 36b McDonald R. J. Org. Chem. 1959; 24: 1580
• 37 Elmore DT, Ogle JR. J. Chem. Soc. 1958; 1141
• 38 Stec J, Huang Q, Pieroni M, Kaiser M, Fomovska A, Mui E, Witola W, Bettis S, McLeod R, Brun R, Kozikowski AP. J. Med. Chem. 2012; 55: 3088
• 39 Roughley SD, Jordan AM. J. Med. Chem. 2011; 54: 3451