[1,2,5]Thiadiazolo[3,4-b]pyrazine-5,6(4H,7H)-dione

Abstract

Fused 1,2,5-chalcogenadiazoles are often used as biologically active compounds and organic optovoltaic materials. [1,2,5]Thiadiazolo[3,4-b]pyrazines are much less studied due to difficulties in their preparation. In this communication, [1,2,5]thiadiazolo[3,4-b]pyrazine-5,6(4H,7H)-dione, a key precursor for the synthesis of 5,6-dihalo-[1,2,5]thiadiazolo[3,4-b]pyrazines, was prepared via condensation of 1,2,5-thiadiazole-3,4-diamine with oxalic acid or oxalyl chloride. The structure of the newly synthesized compound was established by elemental analysis, high-resolution mass spectrometry, ¹H and ¹³C NMR, IR spectroscopy, and mass spectrometry.

1. Introduction

Among the known [1,2,5]chalcogenadiazolo[3,4-b]pyrazines derivatives, 1,2,5-oxadiazoles have been most actively studied. This is due to the availability of 5,6-dichloro-[1,2,5]thiadiazolo[3,4-b]pyrazine, from which a huge number of different biologically active derivatives [1,2,3,4] and energetic materials [5] have been obtained using the aromatic nucleophilic substitution reaction. In the series of selenadiazolopyrazines, 5,6-dihalo-[1,2,5]selenadiazolo[3,4-b]pyrazine remains unknown. Although thiadiazolopyrazines, 5,6-dichloro-[6], and 5,6-dibromo-[1,2,5]thiadiazolo[3,4-b]pyrazines [6] have been described in the literature, their reactions are poorly studied [6,7,8]. This is due to the fact that 5,6-dibromo-[1,2,5]thiadiazolo[3,4-b]pyrazine was prepared from 5,6-dichloro-[1,2,5]thiadiazolo[3,4-b]pyrazine via a rare radical substitution reaction with bromine, and its yield has yet to be reported [6]. However, 5,6-dichloro-[1,2,5]thiadiazolo[3,4-b]pyrazine was obtained from glycine via a four-stage synthesis from malononitrile with a low overall yield (3%), and three of those steps were carried out under very harsh conditions [6,9].

5,6-Dichloro- and 5,6-dibromo-[1,2,5]thiadiazolo[3,4-b]pyrazines can be obtained in a more rational way starting from [1,2,5]thiadiazolo[3,4-b]pyrazine-5,6(4H,7H)-dione 1, similar to the synthesis of 5,6-dichloro-[1,2,5]oxadiazolo[3,4-b]pyrazine [10]. However, the properties and synthesis of thiadiazolopyrazinedione 1 have yet to be described in the literature. There is only an indication of its use as an intermediate [11]. Herein, we report the synthesis of [1,2,5]thiadiazolo[3,4-b]pyrazine-5,6(4H,7H)-dione 1 from 1,2,5-thiadiazole-3,4-diamine 2.

2. Results and Discussion

To synthesize target thiadiazolopyrazinedione 1, we studied the reaction between 1,2,5-thiadiazole-3,4-diamine 2 [12] and oxalic acid or oxalyl chloride (Scheme 1). For the synthesis of thiadiazole 1, we used a previously reported method for the preparation of [1,2,5]oxadiazolo[3,4-b]pyrazine-5,6(4H,7H)-dione: boiling with oxalic acid in dilute hydrochloric acid for 3 h [13]. However, it turned out that in this case, the precipitation of the target product did not occur. Upon evaporation of the aqueous solution, thiadiazole 1 was isolated by EtOAc extraction in 12% yield (

Table 1. Reaction of 1,2,5-thiadiazole-3,4-diamine 2 and oxalic acid or oxalyl chloride.

Entry	Reagent	Solvent	Time, h	Yield of 1, %
1	oxalic acid	dil. HCl	3	12
2	oxalic acid	dil. HCl	6	51
3	oxalyl chloride	glacial AcOH	5	72

, entry 1); the main compound isolated was NH₄Cl, which appears to be formed via the decomposition of diaminothiadiazole 2 or its reaction products in hydrochloric acid. When diaminothiadiazole 2 was refluxed with oxalic acid in acetic acid, the precipitation of target product 1 also failed; however, EtOAc extraction of the treated reaction mixture allowed for the isolation of pyrazinothiadiazole 1 with a yield of 51% (Table 1, entry 2). The best yield of thiadiazolopyrazinedione 1 (72%) was obtained by heating under reflux a mixture of diaminothiadiazole 2 and oxalyl chloride in AcOH for 5 h. In this case, target product 1 was isolated from the reaction mixture by filtration (Table 1, entry 3).

The structure of thiadiazolopyrazinedione 1 was confirmed by elemental analysis, high-resolution mass spectrometry, ¹H and ¹³C NMR, IR spectroscopy, and mass spectrometry. Thiadiazolopyrazinedione 1 can exist both in the form of bis-amide derivative 1 and its bis-enol form 1a, as well as in the form of an equilibrium of the two forms. Unfortunately, analysis of the NMR spectra did not allow us to determine the preference of one of the forms. In the IR spectrum, the presence of a strong band at 1690 cm⁻¹ of the amide signal indicated the presence of diketo derivative 1. It should be noted that the fine structure of similar structures is absent in the literature.

In conclusion, thiadiazolopyrazinedione 1 was synthesized via the condensation reaction of 1,2,5-thiadiazole-3,4-diamine 2 and oxalyl chloride in glacial AcOH. The obtained compound may serve as a precursor for the preparation of 5,6-dihalo-[1,2,5]thiadiazolo[3,4-b]pyrazines.

3. Materials and Methods

1,2,5-Thiadiazole-3,4-diamine 2 was prepared according to the published method [12]. The solvents and reagents were purchased from commercial sources and used as received. Elemental analysis was performed on a 2400 Elemental Analyzer (Perkin ElmerInc., Waltham, MA, USA). ¹H and ¹³C NMR spectra were recorded using a Bruker AM-300 machine (Bruker AXS Handheld Inc., Kennewick, WA, USA) (at frequencies of 300 and 75 MHz) in DMSO-d₆ solution, with TMS as the standard. J values are given in Hz. MS spectrum (EI, 70 eV) was obtained using a Finnigan MAT INCOS 50 instrument (Hazlet, NJ, USA). The IR spectrum was measured using a Bruker “Alpha-T” instrument in a KBr pellet. High-resolution MS spectrum was measured on a Bruker micrOTOF II instrument (Bruker Daltonik Gmbh, Bremen, Germany) using electrospray ionization (ESI).

Synthesis of 5,6-dihydro-[1,2,5]thiadiazolo[3,4-d]pyridazine-4,7-dione 1 (Supplementary Materials).

1,2,5-Thiadiazole-3,4-diamine 2 (223 mg, 2.0 mmol) and oxalyl chloride (0.187 mL, 2.1 mmol) were added to AcOH (4 mL). The mixture was stirred for 5 h at reflux, then cooled to room temperature, water (50 mL) was added, the precipitate was filtered, washed with H₂O (3 × 5 mL), and dried. Yield 245 mg (72%), yellow solid. Mp = 295–296 °C. IR spectrum, ν, cm^–1: 3467, 3406, 3162, 3030, 2729, 1690, 1635, 1541, 1489, 1383, 1338, 800, 665. ¹H NMR (ppm): δ 12.89 (2H, s, NH). ¹³C NMR (ppm): δ 142.0, 155.0. HRMS (ESI-TOF), m/z: calcd for C₄H₂N₄O₂S [M+Na]⁺ 192.9789. Found: 192.9789. MS (EI, 70 eV), m/z (I, %): 170 ([M]⁺, 100), 142 (75), 100 (34), 74 (94), 46 (93), 32 (44). Anal. calcd. for C₄H₂N₄O₄S (170.1504): C, 28.24; H, 1.18, N, 32.93%. Found: C, 28.42; H, 1.34%, N, 33.18%.