Simple and Efficient Synthesis
of N-Nitroethylenediamine Derivatives

Lubomír Kvapil; Adam Šimáček; Martin Grepl; Tomáš Gucký; Tomáš Pospíšil; Pavel Hradil

doi:10.1055/s-0030-1259935

LETTER

Simple and Efficient Synthesis of N-Nitroethylenediamine Derivatives

Lubomír Kvapil^a, Adam Šimáček^b, Martin Grepl^a, Tomáš Gucký^c, Tomáš Pospíšil^c, 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

Abstract

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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

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References

References and Notes

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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.

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.

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