N-Isocyanates, N-Isothiocyanates and Their Masked/Blocked Derivatives: Synthesis and Reactivity

Abstract

In contrast to C-substituted isocyanates which are frequently used reagents in synthesis, nitrogen-substituted isocyanates (N-isocyanates) remained a scientific curiosity in the literature for over a century. The amphoteric character of these reactive intermediates, which results in their propensity to dimerize, prevented the development of their full synthetic potential. In this review, the pioneering work that led to the development of reliable methods for their synthesis, established the existence of such species by spectroscopy, and allowed a delineation of their basic reactivity is presented. The high reactivity of these intermediates has been controlled through the use of masked precursors to regulate their concentration via a reversible equilibrium, a strategy which is also used in industrial processes utilizing C-isocyanates. This control led to the development of more complex reactions, including reaction cascades that allow the rapid synthesis of heterocycles possessing the N–N–C=O motif, which is widely present in agrochemicals and pharmaceuticals. This review covers the literature of N-isocyanates and their sulfur analogues, N-isothiocyanates, until April 2016.

1 Introduction

2 Formation of N-Isocyanates

2.1 Rearrangement of Carbamoyl Azides

2.2 Ring Opening of Heterocycles

2.3 Thermolysis of Hydrazine Derivatives

3 Formation of N-Isothiocyanates

4 Isolation and Observation

4.1 Isolation and Observation of N-Isothiocyanates

4.2 Isolation and Observation of N-Isocyanates

5 Reactivity

5.1 Reactivity of N-Isothiocyanates

5.2 Reactivity of N-Isocyanates

6 Conclusion

Key words

isocyanatoamines - isocyanatoimines - nitrogen-substituted isocyanates - heterocyclic chemistry - cascade reactions - amphoteric reagents

• References


For reviews on isocyanates and their use in industry, see:
• 1a Six C, Richter F. Ullmann’s Encyclopedia of Industrial Chemistry. Vol. 20. Wiley-VCH; Weinheim: 2012: 63-82
• 1b Isocyanates, Organic. In Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Vol. 19 Wiley; New York: 1982: 28-62
• 1c Wang Z. Comprehensive Organic Name Reactions and Reagents. Wiley; New York: 2009

For an entry in the polyurethane literature, see:
• 1d Engels H.-W, Pirkl H.-G, Albers R, Albach RW, Krause J, Hoffman A, Casselmann H, Dormish J. Angew. Chem. Int. Ed. 2013; 52: 9422
• 2a Wicks DA, Wicks ZW. Jr. Prog. Org. Coat. 1999; 36: 148
• 2b Wicks DA, Wicks ZW. Jr. Prog. Org. Coat. 2001; 41: 1
• 2c Wicks ZW. Jr, Jones FN, Pappas SP, Wicks DA. Organic Coatings: Science and Technology. Wiley-VCH; Weinheim: 2007
• 2d Delebecq E, Pascault J.-P, Boutevin B, Ganachaud F. Chem. Rev. 2013; 113: 80
• 3 Such intermediates have also been referred to as isocyanatoamines and isocyanatoimines in the literature; however, the simpler nomenclature (e.g., amino isocyanate) was somewhat more prevalent. The latter nomenclature (e.g., N-isocyanates) is used herein.
• 4 Reichen W. Chem. Rev. 1978; 78: 569
• 5 Wentrup C, Finnerty JJ, Koch R. Curr. Org. Chem. 2011; 15: 1745
• 6 Curtius ZT. Angew. Chem. 1914; 27: 213
• 7a Stollé R. J. Prakt. Chem. 1927; 116: 192
• 7b Stollé R. J. Prakt. Chem. 1928; 117: 185
• 8 Kurz M, Reichen W. Tetrahedron Lett. 1978; 1433
• 9 Lwowski W, DeMauriac R, Mattingly TW. Jr, Scheiffele E. Tetrahedron Lett. 1964; 3285
• 10 Lwowski W, DeMauriac RA, Murray RA, Lunow L. Tetrahedron Lett. 1971; 425
• 11 Reichen W. Helv. Chim. Acta 1976; 59: 2601
• 12 Reichen W. Helv. Chim. Acta 1977; 60: 498
• 13 Del Signore G, Fioravanti S, Pellacani L, Tardella PA. Tetrahedron 2001; 57: 4623
• 14 Wadsworth WS, Emmons WD. J. Org. Chem. 1967; 32: 1279
• 15 Kerber RC, Ryan TJ. J. Org. Chem. 1971; 36: 1566
• 16 Seckinger K. Helv. Chim. Acta 1973; 56: 2061
• 17 Tserng K.-Y, Bauer L. J. Org. Chem. 1973; 38: 3498
• 18 Lockley WJ. S, Ramakrishnan VT, Lwowski W. Tetrahedron Lett. 1974; 2621
• 19 Heep U. Tetrahedron 1975; 31: 77
• 20 Ramakrishnan K, Fulton JB, Warkentin J. Tetrahedron Lett. 1976; 2685
• 21 Gilchrist TL, Rees CW, Tuddenham D. J. Chem. Soc., Perkin Trans. 1 1981; 3214
• 22 Jones DW. J. Chem. Soc., Chem. Commun. 1982; 766
• 23 Theis W, Bethäuser W, Regitz M. Chem. Ber. 1985; 118: 28
• 24 Senet J.-P, Vergne G, Wooden GP. Tetrahedron Lett. 1986; 27: 6319
• 25 Squillacote M, De Felippis J. J. Org. Chem. 1994; 59: 3564

For amidoisocyanates in azapeptide analogues, see:
• 26a Magrath J, Abeles RH. J. Med. Chem. 1992; 35: 4279
• 26b Han H, Janda KD. J. Am. Chem. Soc. 1996; 118: 2539
• 26c Xing R, Hanzlik RP. J. Med. Chem. 1998; 41: 1344
• 27 Busch M. J. Chem. Soc. 1901; 80: 488
• 28 Acree SF. Ber. Dtsch. Chem. Ges. 1903; 36: 3154
• 29 Larsen C, Anthoni U, Christophersen C, Nielsen PH. Acta Chem. Scand. 1969; 23: 322
• 30 Wibers N, Hübler G. Z. Naturforsch. B 1978; 33: 575
• 31 Kirilin AD, Dokuchayev AA, Sokova NB, Chernyshev EA. Russ. Chem. Bull. 1999; 48: 169
• 32 Shah SN, Chudgar KN. Molecules 2000; 5: 657
• 33 Garland K, Gan W, Depatie-Sicard C, Beauchemin AM. Org. Lett. 2013; 15: 4074
• 34a Cranwell PB, Russell AT, Smith CD. Synlett 2016; 27: 131
• 34b Cranwell PB, Russell AT. J. Chem. Educ. 2016; 93: 949
• 35 Kozai S, Takaoka S, Maruyama T. Tetrahedron Lett. 2002; 43: 2633
• 36a Proulx C, Sabatino D, Hopewell R, Spiegel J, García RamosY, Lubell WD. Future Med. Chem. 2011; 3: 1139
• 36b Gante J. Synthesis 1989; 405
• 37 McElhinney RS. J. Chem. Soc. 1966; 950
• 38a El-Hewhi Z, Taeger E, Funge F. J. Prakt. Chem. 1962; 18: 275
• 38b Delépine M. Bull. Soc. Chim. Fr. 1902; 587
• 38c Delépine M, Schving P. Bull. Soc. Chim. Fr. 1910; 896
• 38d Aubert P, Knott EB, Williams LA. J. Chem. Soc. 1951; 2188
• 38e Knott EB. J. Chem. Soc. 1956; 1644
• 39 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1966; 20: 1714
• 40 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1968; 22: 309
• 41 Hünig S, Kiessel M. Chem. Ber. 1958; 91: 380
• 42a Moller J, Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1968; 22: 2493
• 42b Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1969; 23: 537
• 43 Larsen C, Anthoni U, Nielsen PH. Acta Chem. Scand. 1969; 23: 320
• 44 Anthoni U, Berg C. Acta Chem. Scand. 1969; 23: 3602
• 45 Berg C. J. Chem. Soc., Chem. Commun. 1974; 122
• 46 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1967; 21: 2061
• 47 Lwowski W, DeMauriac RA, Thompson M, Wilde RE, Chen S.-Y. J. Org. Chem. 1975; 40: 2608
• 48 Maier G, Teles JH. Chem. Ber. 1989; 122: 745
• 49 Teles JH, Maier G, Hess BA. Jr, Schaad LJ. Chem. Ber. 1989; 122: 749
• 50 Maier G, Naumann M, Reisenauer HP, Eckwert J. Angew. Chem., Int. Ed. Engl. 1996; 35: 1696
• 51 Schulz A, Kalpötke TM. Inorg. Chem. 1996; 35: 4791
• 52 Zeng X, Beckers H, Willner H. Angew. Chem. Int. Ed. 2011; 50: 482
• 53 Zeng X, Gerken M, Beckers H, Willner H. Inorg. Chem. 2010; 49: 9694
• 54 Pasinszki T, Krebsz M, Tarczay G, Wentrup C. J. Org. Chem. 2013; 78: 11985
• 55 Li H, Wan H, Wu Z, Li D, Bégué D, Wentrup C, Zeng X. Chem. Eur. J. 2016; 22: 7856
• 56 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1967; 21: 1201
• 57 Beckett T, Dyson GM. J. Chem. Soc. 1937; 1358
• 58 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1967; 21: 2571
• 59 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1967; 21: 2580
• 60 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1968; 22: 1898
• 61 Anthoni U, Dahl O, Larsen C, Nielsen PH. Acta Chem. Scand. 1969; 23: 943
• 62 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1969; 23: 1439
• 63 Anthoni U, Larsen C, Nielsen PH. Acta Chem. Scand. 1969; 23: 3385
• 64 Larsen C, Jakobsen P. Acta Chem. Scand. 1970; 24: 1445
• 65 Vincent-Rocan J.-F, Clavette C, Leckett K, Beauchemin AM. Chem. Eur. J. 2015; 21: 3886
• 66 Vincent-Rocan J.-F, Derasp JS, Beauchemin AM. Chem. Commun. 2015; 51: 16405
• 67a Alt GH, Chupp JP. Tetrahedron Lett. 1970; 3155
• 67b Chupp JP. J. Heterocycl. Chem. 1971; 8: 571
• 68 Lockley WJ. S, Lwowski W. Tetrahedron Lett. 1974; 4263
• 69 Lwowski W, Kanemasa S, Murray RA, Ramakrishnan VT, Thiruvengadam TK, Yoshida K, Subbaraj A. J. Org. Chem. 1986; 51: 1719
• 70 Gibson HH. Jr, Weissinger K, Abashawl A, Hall G, Lawshae T, LeBlanc K, Moody J, Lwowski W. J. Org. Chem. 1986; 51: 3858
• 71 Roveda J.-G, Clavette C, Hunt AD, Whipp CJ, Gorelsky SI, Beauchemin AM. J. Am. Chem. Soc. 2009; 131: 8740
• 72 Ivanovich RA, Clavette C, Vincent-Rocan J.-F, Roveda J.-G, Gorelski SI, Beauchemin AM. Chem. Eur. J. 2016; 22: 7906
• 73 Clavette C, Gan W, Bongers A, Markiewicz T, Toderian A, Gorelsky SI, Beauchemin AM. J. Am. Chem. Soc. 2012; 134: 16111
• 74 Bongers A, Moon PJ, Beauchemin AM. Angew. Chem. Int. Ed. 2015; 54: 15516
• 75 Gan W, Moon PJ, Clavette C, Das Neves N, Markiewicz T, Toderian AB, Beauchemin AM. Org. Lett. 2013; 15: 1890
• 76 Lavergne K, Bongers A, Betit L, Beauchemin AM. Org. Lett. 2015; 17: 3612
• 77 Clavette C, Vincent-Rocan J.-F, Beauchemin AM. Angew. Chem. Int. Ed. 2013; 52: 12705
• 78 Vincent-Rocan J.-F, Ivanovich RA, Clavette C, Leckett K, Bejjani J, Beauchemin AM. Chem. Sci. 2016; 7: 315

For selected reviews on hydroaminations, see:
• 79a Müller TE, Hultzsch KC, Yus M, Foubelo F, Tada M. Chem. Rev. 2008; 108: 3795
• 79b Müller TE, Beller M. Chem. Rev. 1998; 98: 675
• 79c Bernoud E, Lepori C, Mellah M, Schulz E, Hannedouche J. Catal. Sci. Technol. 2015; 5: 2017

For similar Cope-type hydroamination reactivity of hydrazine derivatives, see:
• 79d Cebrowski PH, Roveda J.-G, Moran J, Gorelsky SI, Beauchemin AM. Chem. Commun. 2008; 492
• 79e Loiseau F, Clavette C, Raymond M, Roveda J.-G, Burrell A, Beauchemin AM. Chem. Commun. 2011; 47: 562
• 79f Beauchemin AM. Org. Biomol. Chem. 2013; 11: 7039
• 80 Ivanovich RA, Vincent-Rocan J.-F, Elkaeed EB, Beauchemin AM. Org. Lett. 2015; 17: 4898
• 81 Derasp JS, Vincent-Rocan J.-F, Beauchemin AM. Org. Lett. 2016; 18: 658
• 82 Shao J, Liu X, Tang P, Luo J, Chen W, Yu Y. Org. Lett. 2015; 17: 4502