Dipropargyl 2,2'-isophthaloylbis(hydrazinecarboxylate)

Abstract

The synthesis of dipropargyl 2,2'-isophthaloylbis(hydrazinecarboxylate) (3) by an addition-elimination reaction between isophthalic dihydrazide (1) and dipropargyl dicarbonate (2) is reported. The title compound was characterized by FT-IR, ¹H NMR, ¹³C NMR, EI-MS, elemental analysis and melting point determination.

Substituted hydrazides have found important applications as traceless linkers for solid-phase synthesis [1] or as synthetic intermediates for the synthesis of pesticides [2], steroids [3], and antimycobacterials [4]. Taking advantage of their donor/acceptor hydrogen-bonding ability, hydrazides have been also used in the formation of molecular duplex strands via interstrand hydrogen bonds [5]. On the other hand, terminal alkynes are versatile functional groups in organic synthesis and materials science mainly due to their characteristic metal-catalyzed reactions [6]. In particular, polyvalent alkynes have emerged as valuable cross-linking agents and monomers in the renowned ‘click’ chemistry [7], with special emphasis on materials science [8,9].

Herein, we report the synthesis of dipropargyl 2,2'-isophthaloylbis(hydrazinecarboxylate) (3) by an addition-elimination reaction between isophthalic dihydrazide (1) and dipropargyl dicarbonate (2) in refluxing acetonitrile (Scheme 1). Symmetrical dipropargyl dicarbonate (2) was prepared from the corresponding propargyl chloroformate [10] following the method reported by Brown and co-workers [11].

Experimental Section

General

¹H and ¹³C NMR spectra were recorded at 25 °C on a Bruker Avance 300 spectrometer in CDCl₃ as solvent, and chemical shifts are reported relative to Me₄Si (δ = 0) [10]. The low-resolution mass spectrum was obtained using a Varian MAT 311A spectrometer. Elemental analysis was performed on a Heraeus Mikro-Rapid analyzer. The infrared spectrum was recorded using a Diamond ATR (attenuated total reflection) accessory (Golden Gate) on a Bio-Rad Excalibur FTS 3000 MX spectrophotometer. The melting point (mp) was measured in a Büchi 510 and is uncorrected. Thin-layer chromatography was carried out on Merck aluminium sheets coated with silica gel 60 F₂₅₄. Compounds were visualized by use of 254 nm UV light and/or iodine as staining reagent. All solvents were of p.a. grade or purified by standard techniques [12]. Anhydrous sodium sulfate was used for drying solutions.

Synthesis of dipropargyl 2,2'-isophthaloylbis(hydrazinecarboxylate) (3): Dipropargyl dicarbonate (2) (500 mg, 2.75 mmol) in CH₃CN (5 mL) was added dropwise to isophthalic dihydrazide (1) (223 mg, 1.15 mmol) in CH₃CN (10 mL) at 0 °C using an ice-water bath. The resulting mixture was vigorously stirred at room temperature for 12 h and further refluxed for 15 min. The solvent was evaporated under reduced pressure, and the residue was washed thoroughly with cold CH₃CN (3 × 10 mL) and Et₂O (3 × 10 mL). Further recrystallization from CH₃CN/MeOH afforded compound 3 (276 mg, 67% yield) as an off-white hygroscopic solid: TLC R_f (CH₂Cl₂/MeOH 4:1) 0.70; m.p. 204–206 °C; ¹H NMR (300 MHz, DMSO-d₆) δ/ppm = 3.57 (s, 2 H), 4.74 (s, 4 H), 7.65 (t, J = 7.6 Hz, 1 H), 8.04 (dd, J = 8.0 Hz, 1.6 Hz, 2 H), 8.35 (s, 1 H), 9.53 (s, 2 H), 10.53 (s, 2 H); ¹³C NMR (75 MHz, DMSO-d₆) δ/ppm = 52.3, 77.6, 78.8, 126.8, 128.8, 130.4, 132.6, 155.4, 165.4; FT-IR (ATR) ν_max (cm⁻¹) 3301, 3238, 3012, 1736, 1656, 1512; MS (ESI) m/z 359 [MH⁺]. Elemental analysis calculated for C₁₆H₁₄N₄O₆ • 1/3 H₂O: C, 52.75; H, 4,06; N, 15.38; found: C, 52.60; H, 4.00; N, 15.62.