tert-Butyl-N-chlorocyanamide: A Novel and Versatile Reagent in Organic Synthesis­

Abstract

The chemistry and applications of tert-butyl-N-chloro­cyanamide in a variety of organic transformations is discussed in this account. The reagent was found to be highly versatile for chlorination and oxidation reactions in organic synthesis. tert-Butyl-N-chlorocyanamide is reactive and possesses a high active chlorine content; it is also safe, soluble in all organic solvents, and recyclable. The reagent is stable, in terms of its active chlorine content, under ambient conditions for a period of more than two years. tert-Butyl-N-chlorocyanamide is able to generate a high level of positive chlorine that is mainly responsible for its involvement in many useful organic transformations, including the conversion of sulfides into sulfoxides, ketoximes into gem-chloronitroso compounds, ald­oximes into hydroximoyl chlorides and 2-isoxazolines, dialkyl and diaryl phosphites into dialkyl and diaryl chlorophosphates, and secondary alcohols into ketones, as well as the coupling of thiols to give disulfides and the oxidative decontamination of sulfur mustard (a chemical warfare agent) and its simulants. In addition, the reagent can undergo photolytic addition to various olefins.

1 Introduction

2 N-Chlorocyanamides

2.1 Basic Chemistry

2.2 Screening of N-Chlorocyanamides

2.3 Synthesis and Characterization of tert-Butyl-N-chlorocyanamide

2.4 General Properties of tert-Butyl-N-chlorocyanamide

2.5 Solubility

2.6 Safety Studies

2.7 Stability studies

3 Chemical Reactivity

3.1 Addition Reactions

3.1.1 Addition to Olefins

3.2 Chlorination Reactions

3.2.1 Conversion of Ketoximes into gem-Chloronitroso Compounds

3.2.2 Conversion of Aldoximes into Hydroximoyl Chlorides and 2-Isoxazolines

3.2.3 Conversion of Dialkyl and Diaryl Phosphites into Dialkyl and Diaryl Chlorophosphates

3.3 Oxidation Reactions

3.3.1 Conversion of Sulfides into Sulfoxides

3.3.2 Decontamination of Sulfur Mustard and Its Simulants

3.3.3 Coupling of Thiols To Give Disulfides

3.3.4 Conversion of Secondary Alcohols into Ketones

4 Conclusions and Perspectives

Key words

N-chloro compounds - tert-butyl-N-chlorocyanamide - addition reactions - chlorinations - oxidations

References

• For reviews covering N-chloro compounds, see:
• 1a Kowalski P. Mitka K. Ossowska K. Kolarska Z. Tetrahedron  2005,  61:  1933 
• 1b Kolvari E. Ghorbani-Choghamarani A. Salehi P. Shirini F. Zolfigol MA. J. Iran. Chem. Soc.  2007,  4:  126 ; and references cited therein
• 1c Koval IV. Russ. J. Org. Chem. (Engl. Transl.)  2002,  38:  301 
• 2 Virgil SC. In Encyclopedia of Reagents for Organic Synthesis   Vol. 7:  Paquette LA. John Wiley & Sons; New York: 1995.  p.1205 
• 3 Kelly RC. In Encyclopedia of Reagents for Organic Synthesis   Vol. 7:  Paquette LA. John Wiley & Sons; New York: 1995.  p.1208 
• 4 Einhorn J. Einhorn C. Ratajczak F. Pierre J.-L. J. Org. Chem.  1996,  61:  7452 
• 5 Liu K.-C. Shelton BR. Howe RK. J. Org. Chem.  1980,  45:  3916 
• 6 Kim KS. Cho IH. Yoo BK. Song YH. Hahn CS. J. Chem. Soc., Chem. Commun.  1984,  762 
• 7 Lee GA. Synthesis  1982,  508 
• 8 Hiegel GA. In Encyclopedia of Reagents for Organic Synthesis   Vol. 7:  Paquette LA. John Wiley & Sons; New York: 1995.  p.1272 
• 9 Tilstam U. Weinmann H. Org. Process Res. Dev.  2002,  4:  384 
• 10 Juenge EC. Beal DA. Tetrahedron Lett.  1968,  9:  5819 
• 11 Cohen T. Kosarych Z. Suzuki K. Yu L.-C. J. Org. Chem.  1985,  50:  2965 
• 12 Walters TR. Zajac WW. Woods JM. J. Org. Chem.  1991,  56:  316 
• 13 Hiegel GA. Nalbandy M. Synth. Commun.  1992,  22:  1589 
• 14 Tilstam U. Harre M. Heckrodt T. Weinmann H. Tetrahedron Lett.  2001,  42:  5385 
• 15 De Luca L. Giacomelli G. Porcheddu A. Org. Lett.  2001,  3:  3041 
• 16 De Luca L. Giacomelli G. Simonetta M. Porcheddu A. J. Org. Chem.  2003,  68:  4999 
• 17 Firouzabadi H. Iranpoor N. Hazarkhani H. Synlett  2001,  1641 
• 18 Zolfigol MA. Choghamarani AG. Hazarkhani H. Synlett  2002,  1002 
• 19 Zolfigol MA. Ghaemi E. Madrakian E. Synlett  2003,  191 
• 20 Wengert M. Sanseverino AM. de Mattos MCS.
  J. Braz. Chem. Soc.  2002,  13:  700 
• 21 Mendonca GF. Sanseverino AM. de Mattos MCS. Synthesis  2003,  45 
• 22 Ye J. Wang Y. Chen J. Liang X. Adv. Synth. Catal.  2004,  346:  691 
• 23 Acharya J. Gupta AK. Shakya PD. Kaushik MP. Tetrahedron Lett.  2005,  46:  5293 
• 24 Rao Z. Zhang X. Baeyens WRG. Talanta  2002,  57:  993 
• 25 Khazaei A. Manesh AA. Synthesis  2005,  1929 
• 26 Skibinska M. Zahn FA. Czarnocka A. Lewenstein W. Acta Pol. Pharm.  1969,  6:  25 
• 27 Campbell MM. Johnson G. Chem. Rev.  1978,  78:  65 
• 28 Brenner DH. In Synthetic Reagents   Vol. 6:  Pizey JS. Wiley; New York: 1985.  p.9 
• 29 Barton DHR. Britten-Kelly MR. Ferreira D. J. Chem. Soc., Perkin Trans. 1  1978,  1090 
• 30 Sharpless KB. Hori T. Truesdale LK. Dietrich CO. J. Am. Chem. Soc.  1976,  98:  269 
• 31 Sharpless KB. Singer SP. J. Org. Chem.  1976,  41:  2504 
• 32 Li G. Chang H.-T. Sharpless KB. Angew. Chem. Int. Ed. Engl.  1996,  35:  451 
• 33 Sharpless KB. Chong AO. Oshima K. J. Org. Chem.  1976,  41:  177 
• 34 Rubin AE. Sharpless KB. Angew. Chem. Int. Ed. Engl.  1997,  36:  2637 
• 35 Rudolph J. Sennhenn PC. Vlaar CP. Sharpless KB. Angew. Chem. Int. Ed. Engl.  1996,  35:  280 
• 36 Li G. Angert HH. Sharpless KB. Angew. Chem. Int. Ed. Engl.  1996,  35:  2813 
• 37 Bruncko M. Schlingloff G. Sharpless KB. Angew. Chem. Int. Ed. Engl.  1997,  36:  1483 
• 38 Reddy KL. Sharpless KB. J. Am. Chem. Soc.  1998,  120:  1207 
• 39 Reddy KL. Dress KR. Sharpless KB. Tetrahedron Lett.  1998,  39:  3667 
• 40 Dawn H.-S. Pitman IH. Young THS. J. Pharm. Sci.  2006,  59:  955 
• 41 Kevin I. Milburn B. Guly DJ. Cox B. Procopiou PA. Org. Lett.  2003,  5:  3313 
• 42 Farook NAM. Kanagaraj M. E-J. Chem.  2004,  1:  1 
• 43 Farook NAM. Mahendran GR. E-J. Chem.  2004,  1:  57 
• 44 Farook NAM. Kumar RS. E-J. Chem.  2004,  1:  65 
• 45 Farook NAM. Murugesan A. E-J. Chem.  2004,  1:  73 
• 46 Farook NAM. Dameem GAS. Kanagaraj M. E-J. Chem.  2004,  1:  132 
• 47 Hunter R. Caira M. Stellenboom N. J. Org. Chem.  2006,  71:  8268 
• 48 Katritzky AR. Vakulenko AV. Jain R. ARKIVOC  2003,  (xiv):  131 
• 49 Hiremath RC. Mayanna SM. Venkatasubramanian N. J. Sci. Ind. Res.  1990,  49:  122 
• 50 Hiremath RC. Jagadeesh RV. . Mayanna SM. J. Chem. Sci.  2005,  117:  333 
• 51 Channegowda C. Mayanna SM. Microchim. Acta  1990,  271 
• 52 Gupta AK. Acharya J. Pardasani D. Dubey DK. Tetrahedron Lett.  2007,  48:  767 
• 53 Dubey DK. Malhotra RC. Vaidyanathaswamy R. Vijayraghavan R. J. Org. Chem.  1993,  64:  8301 
• 54 Vijayraghavan R. Kumar P. Dubey DK. Singh R. Biomed. Environ. Sci.  2002,  15:  25 
• 55 Shakya PD. Dubey DK. Pardasani D. Palit M. Gupta AK. J. Chem. Res.  2005,  821 
• 56 Sathe M. Karade H. Kaushik MP. Chem. Lett.  2007,  36:  996 
• 57 Neale RS. Marcus NL. J. Org. Chem.  1969,  34:  1808 
• 58 Ghosh S. Baul S. Synth. Commun.  2001,  31:  2783 
• 60a Patel BK. In Kirk-Othmer Encyclopedia of Chemical Technology   4th ed., Vol. 7:  Kroschwitz JI. Howe-Grant M. John Wiley & Sons; New York: 2003.  p.736 
• 60b Rodd’s Chemistry of Carbon Compounds   2nd ed., Vol. 1C:  Coffey S. Elsevier; Amsterdam: 1965. 
• 60c Kukushkin VY. Pombeiro AJL. Chem. Rev.  2002,  102:  1771 
• 60d Michelin RA. Mozzon M. Bertani R. Coord. Chem. Rev.  1996,  147:  299 
• 60e Ray P. Chem. Rev.  1961,  61:  313 
• 61 Kumar V. Synlett  2005,  1638 
• 62 Benders PH. Hackman IT. Recl. Trav. Chim. Pays-Bas  1972,  91:  343 
• 63a

  See also ref. 59

• 63b Banks RE. Burling ED. J. Chem. Soc.  1965,  6077 
• 64 Yang YC. Baker JA. Ward JR. Chem. Rev.  1992,  92:  1729 
• 65a Kruglyak YL. Landau MA. Leibovskaya GA. Martynov IV. Saltykova LI. Zh. Obshch. Khim.  1971,  41:  2338 
• 65b Cecherelli P. Curini M. Epifano F. Marcotullio MC. Rosati O. Tetrahedron Lett.  1980,  39:  4385 
• 65c Sabuni M. Kresz G. Braun H. Tetrahedron Lett.  1984,  25:  5377 
• 65d Martynov IV. Chepakova LA. Brel VK. Sokolov VB. Zh. Obshch. Khim.  1986,  56:  2020 
• 65e

  See also ref. 12

• 65f Tordeux M. Boumizane K. Wakselman C. J. Org. Chem.  1993,  58:  1939 
• 65g Wang YC. Lu TM. Elango S. Lin CK. Tsai CT. Van T H. Tetrahedron: Asymmetry  2002,  13:  691 
• 66 Kumar V. Kaushik MP. Tetrahedron Lett.  2005,  46:  8121 
• 67a Kozikowski AP. Acc. Chem. Res.  1984,  17:  410 
• 67b Kanemasa S. Tsuge O. Heterocycles  1990,  30:  719 
• 67c Esipenko AA. Samarai LI. Russ. Chem. Rev. (Engl. Transl.)  1993,  62:  1097 
• 67d Caramella P. Grunanger P. Nitrile Oxides and Imines, In 1,3-Dipolar Cycloaddition Chemistry   Vol. 1:  Padwa A. Wiley; New York: 1984.  Chap. 3. p.291 
• 67e Torssell K. Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis   VCH; New York: 1988. 
• 67f Grünanger P. Vita-Finzi P. Isoxazoles, In The Chemistry of Heterocyclic Compounds   Part 1, Vol. 49:  Wiley; New York: 1991. 
• 68a Shankar BB. Yang DY. Girton S. Ganguly AK. Tetrahedron Lett.  1998,  39:  2447 
• 68b Sammelson RE. Ma T. Galietta LJV. Verkman AS. Kurth MJ. Bioorg. Med. Chem. Lett.  2003,  13:  2509 
• 68c Bal G. der Venken PV. Antonov D. Lambeir A.-M. Grellier P. Croft SL. Augustyns K. Haemers A. Bioorg. Med. Chem. Lett.  2003,  13:  2875 
• 69 Kumar V. Kaushik MP. Tetrahedron Lett.  2006,  47:  1457 
• 70a Eto M. In Organophosphorus Pesticides: Organic and Biological Chemistry   CRC; Cleveland OH: 1974.  p.18 
• 70b Van Wazer JR. Phosphorus and its Compounds   Vol. II:  Interscience; New York: 1961. 
• 70c Engel R. Chem. Rev.  1977,  77:  349 
• 70d Kosolapoff GM. In Organic Phosphorus Compounds   Vol. 6:  Wiley-Interscience; New York: 1950.  p.503 
• 71 Kumar V. Kaushik MP. Chem. Lett.  2006,  35:  312 
• 72a Holland HL. Chem. Rev.  1988,  88:  473 
• 72b Block E. Angew. Chem., Int. Ed. Engl.  1992,  31:  1135 
• 72c Durst T. In Comprehensive Organic Chemistry   Vol. 3:  Barton D. Ollis WD. Pergamon; Oxford: 1979.  p.121 
• 72d Carreno MC. Chem. Rev.  1995,  95:  1717 
• 72e Solladie G. Synthesis  1981,  185 
• 72f Ikemoto N. Schrieber SL. J. Am. Chem. Soc.  1990,  112:  9657 
• 72g Berkowitz DB. Danishefsky SJ. Schulte GK. J. Am. Chem. Soc.  1992,  114:  4518 
• 73 Kumar V. Kaushik MP. Chem. Lett.  2005,  34:  1230 
• 74a Papirmeister B. Feister AJ. Robinson SI. Ford RD. Medical defense against mustard gas: Toxic mechanism and medical implications   CRC; Boca Raton FL: 1991.  p.359 
• 74b Pechura CM. Rail DP. The health effects of mustard gas and lewisite   National Academic Press; Washington DC: 1993.  p.428 
• 75 Kumar V. Kaushik MP. Synth Commun.  2006,  36:  2385 
• 76 Davis FA. Jenkins R. Yocklovich SG. Tetrahedron Lett.  1978,  19:  5171 
• 77 Chemistry of Bivalent Sulfur   Reid EE. Chemical Publishing Co.; New York: 1960.  Chap. 5.
• 78 Anslow JR. Karnofsky DA. Valjager B. Smith HW. J. Pharmacol. Exp. Ther.  1948,  93:  1 
• 79a Oae S. Organic Sulfur Chemistry: Structure and Mechanism   Vol. 1:  CRC; Boca Raton FL: 1991. 
• 79b Cremlyn RJ. An Introduction to Organosulfur Chemistry   John Wiley & Sons; New York: 1996. 
• 79c Ogawa A. Nishiyama Y. Kambe N. Murai S. Sonoda N. Tetrahedron Lett.  1987,  28:  3271 
• 79d Bischoff L. David C. Martin L. Meudal H. Roques B.-P. Fournié-Zaluski M.-C. J. Org. Chem.  1997,  62:  4848 
• 80 Kumar V. Kaushik MP. Bull. Chem. Soc. Jpn.  2007, in press
• 81a Hudlicky M. Oxidations in Organic Chemistry   ACS Monograph 186; Washington DC: 1990. 
• 81b Sheldon RA. Kochi JK. Metal-Catalyzed Oxidations of Organic Compounds   Academic; New York: 1981. 
• 81c Sheldon RA. Arends IWCE. ten Brink G.-J. Dijksman A. Acc. Chem. Res.  2002,  35:  774 

59

Kumar, V.; Kaushik, M. P. unpublished results.

82

Kumar, V.; Kaushik, M. P., unpublished results.