Three-component and one-pot synthesis of 3-aryl-2,4-diselenoxo-1,3,5-triazepane-6,7-diones

Abstract

A simple, one-pot synthesis of six 3-aryl-2,4-diselenoxo-1,3,5-triazepane-6,7-diones has been achieved in moderate to good yields via a three-component condensation of variously substituted anilines, oxalyl chloride, and two molecules of potassium selenocyanate in acetone at room temperature.

Multicomponent reactions (MCRs) have been frequently used by synthetic chemists as a facile means to generate molecular diversity from bifunctional substrates that react sequentially in an intramolecular fashion. ¹ Molecules with triazepine skeletons have attracted much attention as a result of their interesting biological properties. ² Triazepanediones represent a particular subset, of which a number of functional isomers have been synthesized.^3–5 Applications of compounds with triazepanedione skeletons have been reported. ⁶ With regard to monocyclic triazepines, ⁷ 1,2,4-triazepines have been prepared by the cycloaddition of 1-azirines to 1,2,4,5-tetrazines ⁸ or by a photochemical walk rearrangement of 3,4,7-triaza-2,4-norcaradienes. ⁹ Although the synthesis of seven-membered [1,2,4]-triazepine derivatives is well precedent in the literature,^10–12 few reports are known for [1,2,5]-triazepine systems.^13–17 The current interest in selenium-containing organic compounds stems from their remarkable synthetic and biological functions.^18–22 The first synthesis of acyl isoselenocyanates, which were generated by the reaction of acyl chlorides and potassium selenocyanate, has been described by Douglas. ²³

Recently, a synthesis of 3-aryl-2,4-dithioxo-1,3,5-triazepane-6,7-diones from oxalyl chloride, anilines, and two molecules of ammonium thiocyanate in acetone was reported. ²⁴ Herein, we describe a synthesis of the seleno analog, namely 3-aryl-2,4-diselenoxo-1,3,5-triazepane-6,7-diones, from variously substituted anilines, oxalyl chloride, and two molecules of potassium selenocyanate in acetone at room temperature using a reported method. ²⁴

Results and discussion

A recent report ²⁴ described the synthesis of a series of 3-aryl-2,4-dithioxo-1,3,5-triazepane-6,7-diones by the reaction between oxalyl chloride, anilines, and two molecules of ammonium thiocyanate (NH₄SCN) in acetone under ultrasound irradiation. We thought that a synthesis of some analogues of the 3-aryl-2,4-diselenoxo-1,3,5-triazepane-6,7-diones, 3-aryl-2,4-diselenoxo-1,3,5-triazepane-6,7-diones (4) might be simply achieved by a similar reaction in which ammonium thiocyanate was replaced by potassium selenocyanate (3) (Scheme 1).

Scheme 1.

The reaction of substituted anilines, oxalyl chlorideand two molecules of potassium selenocyanate inacetone at room temperature.

So it proved, and a series of six such compounds were prepared in good yield using a variety of substituted anilines (1; R = various) in reaction with oxalyl chloride (2) and KSeCN (3) (Table 1).

Table 1.

Yields of a series of 3-aryl-2,4-diselenoxo-1,3,5-triazepane-6,7-diones (4) prepared from anilines (1), an oxalyl chloride (2), and KSeCN (3).

4	R	Yield a (%)	M.p. (°C)
a	H	80	211–213
b	4-CH3	86	226–228
c	2-CH3	84	163–165
d	4-CN	75	137–139
e	4-NO2	80	150–152
f	3-Cl	75	178–180

a

Yields refer to the pure isolated products.

The structures of compounds 4a–f were deduced from their elemental analyses and their IR, ¹H NMR, ¹³C NMR spectra. The mass spectra of compounds 4a–f are fairly similar and display molecular ion peaks. For example, the mass spectrum of the simplest 3-phenyl compound (4a) showed a molecular ion peak at 359 confirming that it is a (1:1:2) adduct of aniline, oxalyl chloride, and two molecules of potassium selenocyanate. The IR spectrum showed an absorption bond at 3392 cm⁻¹ for NH group and exhibited two absorption bands at 1621 cm⁻¹ for the C=O and 1263 cm⁻¹ for the C=Se groups. The 500 MHz ¹H NMR spectrum of 4a exhibited multiplet signal at δ 7.25–7.71 ppm for aromatic protons. A single signal was observed at 9.22 ppm that disappeared after addition of a few drops of D₂O to the DMSO-d₆ solution of compound 4a. This signal is related to NH proton. The ¹³C NMR spectrum of compound 4a showed six distinct resonances in agreement with the proposed structure.

A tentative mechanism for this transformation is proposed in Scheme 2. It is conceivable that oxalyl diisoselenocyanate 5 was prepared from the reaction of two equivalents of KSeCN 3 with one equivalent of oxalyl chloride 1. Later 5 followed by addition of anilines 1 to generate 6. subsequent cyclization of Intermediate 6, which is converted into for 4 by intramolecular cyclization.

Scheme 2.

Suggested mechanism for formation of compound 4.

Experimental

Melting points were determined with an Electrothermal 9100 apparatus and are uncorrected. Elemental analyses for C and H were performed using a Heraeus CHN-O-Rapid analyzer. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470 spectrometer. NMR spectra were obtained on a Bruker DRX 500 Avance spectrometer (¹H NMR at 500 Hz, ¹³C NMR at 125 Hz) in DMSO-d₆ using TMS as an internal standard. Chemical shifts (δ) are given in parts per million (ppm). All of the chemicals used in this study were purchased from Merck and Fluka (Buchs, Switzerland) and were used without further purification.

Caution! All of the reactions involving selenium-containing compounds should be carried out in a well-ventilated hood.

General procedure

To a solution of potassium selenocyanate (2 mmol) in dry acetone (3 mL) was added oxalyl chloride (1 mmol) in dry acetone (3 mL). The reaction mixture was stirred at r.t. for 10 min. Anilines (1 mmol) in dry acetone (4 mL) was added to the mixture and stirring was continued at r.t. for 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the resulting precipitate was collected by filtration on a Buchner funnel and washed with cold water (20 mL) and recrystallized from EtOH to afford the pure title compounds.

3-Phenyl-2,4-diselenoxo-1,3,5-triazepane-6,7-dione (4a): Brown powder; m.p. 211 °C–213 °C; IR (KBr) (ν_max, cm⁻¹): 3392, 1673, 1621, 1520, 1263; ¹H NMR: δ 7.25–7.71 (m, 5H, ArH), 9.22 (s, 2H, N–H) ppm; ¹³C NMR: δ 119.5, 125.4, 129.1, 136.0, 158.2, 169.2 ppm; MS (m/z, %): 359 (6); Anal. calcd for C₁₀H₇N₃O₂Se₂: C, 33.45; H, 1.96; N, 11.70; found: C, 33.58; H, 2.11; N, 11.59%.

3-(4-Methylphenyl)-2,4-diselenoxo-1,3,5-triazepane-6,7-dione (4b): Brown powder; m.p. 226 °C–228 °C; IR (KBr) (ν_max, cm⁻¹): 3384, 1680, 1637, 1514, 1260; ¹H NMR: δ 2.33 (s, 3H, CH₃). 7.27 (d, 2H, ³J = 8.0, ArH), 7.61 (d, 2H, ³J = 8.0, ArH), 9.46 (s, 2H, N–H) ppm; ¹³C NMR: δ 21.5, 119.6, 129.8, 133.61, 135.5, 157.3, 169.0 ppm; MS (m/z, %): 373 (8); Anal. calcd for C₁₁H₉N₃O₂Se₂: C, 35.41; H, 2.43; N, 11.26; found: C, 35.52; H, 2.57; N, 11.40%.

3-(2-Methylphenyl)-2,4-diselenoxo-1,3,5-triazepane-6,7-dione (4c): Brown powder; m.p. 163 °C–165 °C; IR (KBr) (ν_max, cm⁻¹): 3337, 1658, 1649, 1510, 1267; ¹H NMR: δ 2.47 (s, 3H, CH₃), 7.16–8.23 (m, 4H, ArH), 9.55 (s, 2H, N–H) ppm; ¹³C NMR: δ 18.4, 121.3, 125.6, 127.2, 129.4, 130.8, 134.5, 157.5, 168.9 ppm; MS (m/z, %): 373 (5); Anal. calcd for C₁₁H₉N₃O₂Se₂: C, 35.41; H, 2.43; N, 11.26; found: C, 35.54; H, 2.53; N, 11.37%.

4-(6,7-Dioxo-2,4-diselenoxo-1,3,5-triazepan-3-yl)benzonitrile (4d): Brown powder; m.p. 137 °C–139 °C; IR (KBr) (ν_max, cm⁻¹): 3330, 2231, 1668, 1581, 1496, 1270; ¹H NMR: δ 7.38 (d, 2H, ³J = 8.0, ArH), 7.53 (d, 2H, ³J = 8.0, ArH), 9.30 (s, 2H, N–H) ppm; ¹³C NMR: δ 108.1, 129.2, 131.4, 136.5, 144.6, 156.1, 169.4 ppm; MS (m/z, %): 384 (3); Anal. calcd for C₁₁H₆N₄O₂Se₂: C, 34.40; H, 1.57; N, 14.59; found: C, 34.52; H, 1.70; N, 14.46%.

3-(4-Nitrophenyl)-2,4-diselenoxo-1,3,5-triazepane-6,7-dione (4e): Brown powder; m.p. 150 °C–152 °C; IR (KBr) (ν_max, cm⁻¹): 3392, 1670, 1545, 1468, 1373, 1280; ¹H NMR: δ 7.52 (d, 2H, ³J = 7.2, ArH), 7.71 (d, 2H, ³J = 7.2, ArH), 9.40 (s, 2H, N–H) ppm; ¹³C NMR: δ 132.0, 135.6, 137.1, 149.2, 156.3, 169.7 ppm; MS (m/z, %): 404 (7); Anal. calcd for C₁₀H₆N₄O₄Se₂: C, 29.72; H, 1.50; N, 13.86; found: C, 29.60; H, 1.65; N, 14.00%.

3-(3-Chlorophenyl)-2,4-diselenoxo-1,3,5-triazepane-6,7-dione (4f): Brown powder; m.p. 178 °C–180 °C; IR (KBr) (ν_max, cm⁻¹): 3310, 1675, 1512, 1438, 1255; ¹H NMR: δ 7.18–7.54 (m, 4H, ArH), 9.33 (s, 2H, N–H) ppm; ¹³C NMR: δ 128.2, 128.9, 130.3, 131.7, 139.6, 143.1, 156.5, 169.5 ppm; MS (m/z, %): 393 (5); Anal. calcd for C₁₀H₆ClN₃O₂Se₂: C, 30.52; H, 1.54; N, 10.68; found: C, 30.61; H, 1.67; N, 10.80%.