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Synlett 2011(8): 1168-1170  
DOI: 10.1055/s-0030-1259935
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Simple and Efficient Synthesis of N-Nitroethylenediamine Derivatives

Lubomír Kvapila, Adam Šimáčekb, Martin Grepla, Tomáš Guckýc, Tomáš Pospíšilc, Pavel Hradil*a,b
a Farmak a.s., 771 17 Olomouc, Czech Republic
Fax: +420585634465; e-Mail: ph.1@tiscali.cz;
b Department of Organic Chemistry, Palacky University, Tr. 17. Listopadu 12, 771 46 Olomouc, Czech Republic
c Laboratory of Growth Regulators, Palacky University, Slechtitelu 11, 783 71 Olomouc, Czech Republic
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Publication History

Received 13 December 2010
Publication Date:
07 April 2011 (online)

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Abstract

A simple and efficient synthesis of N-nitroethylenediamine derivatives was carried out by reaction of 1-nitroimidazolidin-2-one with various nitrogen-, oxygen-, and sulfur-containing nucleophiles. The reactivity of primary and secondary amines, amino alcohols, hydrazines, amino acids, alcohols, and thiophenol was tested.

Key words

nucleophiles - ring opening - N-nitroethylenediamine derivatives - nitroamines

    References and Notes

  • 1 Saibabu Koti SRS. Timmons C. Li G. Chem. Biol. Drug Des.  2006,  67:  101 
    Google Scholar
  • For recent examples, see:
  • 2a Diaz-Valenzuela MB. Philips SD. France MB. Gunn ME. Clarke ML. Chem. Eur. J.  2009,  15:  1227 
    Google Scholar
  • 2b Uchida T. Katsuki T. Tetrahedron Lett.  2009,  50:  4741 
    Google Scholar
  • 2c Fu X. Loh W.-T. Zhang Y. Chen T. Ma T. Liu H. Wang J. Tan C.-H. Angew. Chem. Int. Ed.  2009,  48:  7387 
    Google Scholar
  • 2d Yang X. Liu H. Fu H. Qiao R. Jiang Y. Zhao Y. Synlett  2010,  101 
    Google Scholar
  • For recent examples, see:
  • 3a Sriramurthy V. Barcan GA. Kwon O. J. Am. Chem. Soc.  2007,  129:  1298 
    Google Scholar
  • 3b Murai K. Takaichi N. Takahara Y. Fukushima S. Fujioka H. Synthesis  2010,  520 
    Google Scholar
  • 3c Hari GS. Lee YR. Synthesis  2010,  453 
    Google Scholar
  • 4 Agrawal JP. Hodgson RD. Organic Chemistry of Explosives   Wiley; New York: 2007. 
    Google Scholar
  • 5 Ledgard JB. The Preparatory Manual of Explosives   3rd ed.:  Jared Ledgard; Washington: 2007. 
    Google Scholar
  • 6 Chilton WS. Hsu ChP. Phytochemistry  1975,  14:  2291 
    CrossrefGoogle Scholar
  • 7 Miyazaki Y. Kono Y. Shimazu A. Takeuchi S. Yonehara H. J. Antibiot.  1968,  21:  279 
    CrossrefGoogle Scholar
  • 8 Bachmann WE. Horton WJ. Jenner EL. MacNaughton NW. Maxwell CE. J. Am. Chem. Soc.  1950,  72:  3132 
    CrossrefGoogle Scholar
  • 9 Krapcho AP, Menta E, Oliva A, and Spinelli S. inventors; US  5519029.  ; Chem. Abstr. 1994, 121, 157651
  • 10 Astakhov M. Stepanov RS. Kruglyakova LA. Kekin YV. Russ. J. Org. Chem.  2000,  36:  575 
    Google Scholar
11

Procedure for the Preparation of 1,3-Bis[2-(nitroamino)-ethyl]urea (5) Starting material 4 (2.0 g, 15.26 mmol) was suspended in H2O (10 mL). To this suspension was added dropwise 10% NaOH (10 mL); the starting material 4 dissolved. After 1 h stirring at laboratory temperature the reaction mixture was acidified with dilute HCl to pH 2. Product 5 crystallized from this solution in 72% yield (1.3 g) as colorless crystals. C5H12N6O5 (236.18); mp 161-163 ˚C. MS: m/z (rel. abundance) = 175.1 (14) [NO2NHCH2CH2NHCONHCH2CH2]+. ¹H NMR (300 MHz, DMSO-d 6): δ = 3.16 (q, 4 H, J = 5.9 Hz, H4, H4′), 3.42 (t, 4 H, J = 5.9 Hz, H3, H3′), 6.19 (t, 2 H, J = 5.9 Hz, NH-5, NH-5′), 11.98 (br s, 2 H, NH-2, NH-2′). ¹³C NMR (75 MHz, DMSO-d 6): δ = 36.5, 45.5, 158.0.

12

Representative Experimental Procedure for the Preparation of 1-(2-Hydroxyethyl)-3-[2-(nitroamino)-ethyl]urea (31) Starting material 4 (1.0 g, 7.63 mmol) was dissolved in MeOH (30 mL) and 2-aminoethanol (0.5 g, 8.18 mmol, 1.07 equiv) was added. The reaction mixture was heated to boiling and periodically analyzed using TLC (mobile phase: EtOAc). After 2 h the spot corresponding to 4 disappeared, the reaction mixture was concentrated to crystallization, and the crude product was filtered. Recrystallization from i-PrOH-toluene afforded 31 as colourless crystals (1.18 g, 81%). C5H12N4O4 (192.17); mp 101-103 ˚C. MS: m/z (%) = 131.0(16) [HO(CH2)2NHCONHCH2CH2]+. ¹H NMR (300 MHz, DMSO-d 6): δ = 3.03 (q, 2 H, J = 5.6 Hz, H-8), 3.15 (q, 2 H, J = 5.8 Hz, H-4), 3.17-3.40 (m, 4 H, H-3, H-9), 4.73 (br s, 1 H, OH), 6.03 (t, 1 H, J = 5.6 Hz, NH-7), 6.14 (t, 1 H, J = 5.8 Hz, NH-5), 11.0 (s, 1 H, NH-2). ¹³C NMR, (75 MHz, DMSO-d 6): δ = 36.5, 42.0, 46.6, 61.1, 158.
Spectroscopic Data for Selected Products1-[2-(Nitroamino)ethyl]urea (6) C3H8N4O3 (148.12); mp 97-99 ˚C. MS: m/z (%) = 87.1 (100) [NH2CONHCH2CH2]+. ¹H NMR (300 MHz, DMSO-d 6): δ = 3.14 (q, 2 H, J = 5.9 Hz, H-4), 3.41 (t, 2 H, J = 5.9 Hz, H-3), 5.57 (s, 2 H, NH2), 6.10 (t, 1 H, J = 5.5 Hz, NH-5), 12.00 (s, 1 H, NH-2). ¹³C NMR (75 MHz, DMSO-d 6): δ = 36.4, 45.7, 158.7.
N -[2-(Nitroamino)ethyl]hydrazinecarboxamide (34) C3H9N5O3 (163.13); mp 129-131 ˚C. MS: m/z (%) = 163.9 (2) [M + H+], 102.0(100) [NH2NHCONHCH2CH2]+. ¹H NMR (300 MHz, DMSO-d 6): δ = 3.13-3.23 (m, 4 H, H-3, H-4), 5.96 (br s, 3 H, NH2, NH-7), 6.46 (br s, 1 H, NH-5), 7.04 (s, 1 H, NH-2). ¹³C NMR (75 MHz, DMSO-d 6): δ = 37.55, 50.01, 160.33.
Methyl [2-(Nitroamino)ethyl]carbamate (41) C4H9N3O4 (163.13); mp 86-87.5 ˚C. MS: m/z (%) = 163.7 (4) [M + H]+, 102.1 (100) [CH3OCONHCH2CH2]+. ¹H NMR (300 MHz, DMSO-d 6): δ = 3.15 (q, 2 H, J = 5.98 Hz, H-4), 3.43 (t, 2 H, J = 6.00 Hz, H-3), 3.52 (s, 3 H, CH3), 7.25 (t, 1 H, J = 5.1 Hz, NH-5), 12.00 (s, 1 H, NH-2). ¹³C NMR (75 MHz, DMSO-d 6): δ = 37.57, 44.67, 51.36, 156.77.
S -Phenyl [2-(Nitroamino)ethyl]thiocarbamate (43) C9H11N3O3S (241.26); mp 109-111 ˚C. MS: m/z (%): 180 (53) [C6H5SCONHCH2CH2]+. ¹H NMR (300 MHz, DMSO-d 6): δ = 3.30 (q, 2 H, J = 5.4 Hz, CH2), 3.47 (t, 2 H, J = 5.4 Hz, CH2), 7.36-7.47 (m, 5 H, ArH), 8.46 (t, 1 H, J = 5.4 Hz, NH), 12.07 (br s, 1 H, NH). ¹³C NMR (300 MHz, DMSO-d 6): δ = 33.9, 37.9, 127.1, 128.8, 129.4, 134.8, 164.3.