2-[3,5-Bis(5-bromothien-2-yl)-4H-1,2,6-thiadiazin-4-ylidene]-malononitrile

Abstract

Bromination of 2-[3,5-di(thien-2-yl)-4H-1,2,6-thiadiazin-4-ylidene]-malononitrile with N-bromosuccinimide in THF, at ca. 20 °C for 24 h gave 2-[3,5-bis(5-bromothien-2-yl)-4H-1,2,6-thiadiazin-4-ylidene]-malononitrile in 82% yield. The latter is intended as a scaffold for preparing donors for organic photovoltaics.

1. Introduction

Thiophenes are extensively researched heterocycles with a wide range of applications in medicinal chemistry and materials science. Their chemistry and applications have been reviewed [1,2]. Examples of thiophene-containing drugs are the antipsychotic Olanzapine, the antifungal Tioconazole and the antiplatelet Clopidogrel (Figure 1). In the materials sciences, thiophenes find uses in Covalent Organic Frameworks [3], as components of organic solar cells [4] and as sensors [5].

Recently, we synthesized a series of thiophene-containing small-molecule non-S-oxidized 4H-1,2,6-thiadiazin-4-ones 2 derived from 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (1) (Scheme 1) and evaluated their performance as electron donors in solution-processed bulk heterojunction (BHJ) solar cells. When paired with PC₇₀BM, these small-molecule donors achieved power conversion efficiencies (PCEs) of approximately 3% in BHJ solar cells [6]. In subsequent research, polymers containing 4H-1,2,6-thiadiazine units demonstrated PCEs of up to 3.8% [7]. These poor PCE values were attributed to moderate short circuit current (J_sc) and fill factor (FF) values (best obtained were 8.2 mA/cm² and 33%, respectively). These performance characteristics were linked to the relatively high electron affinity (EA) energies of the donors (−3.52 to −3.41 eV). To achieve higher PCEs in organic photovoltaics (OPVs) employing PCBM as the acceptor, the ideal LUMO energy of the donor needs to be as low as −4.0 eV [8]. An electrochemical study of selected 1,2,6-thiadiazines [9], showed that dicyanoylidene 3 (Scheme 1) has an ideal EA value (−4.01 eV), indicating that the incorporation of this unit in donor molecules could lead to improved optoelectronic properties. This requires access to a suitable halo-substituted analogue of 3 for Pd coupling typically used for the synthesis of oligomers or polymers [6,7]. As such, a suitable dibromo derivative was synthesized as a potential scaffold for these transformations.

2. Results and Discussion

Similar bromination reactions of thienyl-thiadiazinone were readily achieved using 2 equiv. of N-bromosuccinimide (NBS) [6]. Consequently, we applied these conditions for this bromination. However, the electron-withdrawing nature of the dicyanoylidene group diminished the reactivity of the thiophene rings, requiring an excess of NBS and an extended reaction time to achieve the formation of bis-bromothiophene 4 in 82% yield (Scheme 2). The product was isolated as orange needles [mp (DSC) onset 71.6 °C (from EtOH)], while its yellow color in solution [λ_max (DCM) 483 nm, log ε 3.25] indicates the presence of the thiadiazine chromophore. Mass spectrometry [m/z 482 (M⁺)] revealed a characteristic isotope pattern to the presence of two bromine atoms. The IR spectrum revealed the presence of a C≡N stretching band at 2216 cm⁻¹ due to the dicyanoylidene functionality, while ¹H and ¹³C NMR spectroscopy (see Supplementary Materials) supported a symmetric structure.

Single crystals were prepared by a hot ethanol recrystallisation and the structure was supported by single-crystal X-ray diffraction studies (Figure 2). The thiadiazine moiety of 4 adopts a shallow boat conformation, with the respective planes defined by N(2)–S(1)–N(1) and C(3)–C(2)–C(1) inclined by ca. 45° with respect to the C1-N1-N2-C3 plane. Presumably, this distortion helps overcome the buildup of steric compression between the neighboring bulky dicyanomethylene and thienyl substituents. Moreover, torsion was observed between the thiadiazine and thiophene rings (torsion angles 27.6 and 12.8°). Bird’s aromaticity index (I_A), based upon the statistical evaluation of deviations in peripheral bond orders derived from experimental bond lengths [10,11,12], gives I_A 68, which is higher than 2-(3,5-dichloro-4H-1,2,6-thiadiazin-4-ylidene)-malononitrile (I_A 60, [13]) and indicates modest aromaticity (cf. I_A 53 for furan and 100 for benzene).

Interestingly, in the solid phase, an intermolecular interaction was observed between C≡N…Br (d = 3.131 and 3.312 Å) (Figure 3). The C≡N…Br angles of 144 and 152° suggest electron donation from the nitrile nitrogen lone pair into the σ hole of the bromine atom. Other C≡N…Br interactions have been reported in the literature [14,15], while a similar interaction between the nitrogen lone pair and the σ hole of an iodine atom was recently reported [16].

DFT calculations at the RB3LYP/6-311G(d) level were conducted to further study the electrochemical properties of the synthesized molecule and its potential derivatives. This method has been validated for assessing the suitability of thiadiazines in OPVs [7]. Dibromothiophene 4 showed deeper HOMO and LUMO levels with a decreased band gap compared to its parent analogue 3 (

Table 1. CV and UV-vis data of 5,5′-bis [9-(2-ethylhexyl)-9H-carbazol-3-yl]-4,4′-diphenyl-2,2′-bithiazole (4). All the values correspond to peak onsets.

Compound	EHOMODFT (eV) [a]	ELUMOTD-DFT (eV) [b]	EgTD-DFT (eV) [c]
3	−6.26	−3.72	2.54
4	−6.34	−3.90	2.44
5	−5.80	−3.65	2.15
6	−5.55	−2.99	2.56

^[a]E_HOMO^DFT was obtained from geometry optimizations at the DFT/RB3LYP 6-311G(d) level of theory. ^[b] E_LUMO^TD-DFT = E_HOMO^DFT + E_g^TD-DFT. ^[c] E_g^TD-DFT = first excitation energy from TD-DFT/RB3LYP 6-311G(d).

). This shift would make compound 4 less suitable for donor molecules in OPVs; however, its use as a scaffold to perform Pd-catalyzed C-C coupling could lead to more conjugated derivatives such as tetrathienyl analogue 5 (Table 1). The potential tetrathienyl derivative 5 (Figure 4) was compared with the ketone analogue 6 showing that, as expected, the dicyanoylidene had a lower band gap (2.15 vs. 2.56 eV) and a deeper LUMO value (−3.65 vs. −2.99 eV) compared to the ketone (Table 1). This shows that compounds like ylidene 5 could be useful for the preparation of donor molecules for OPVs.

The synthesis of dibromothiophene 4 can allow for the preparation of more efficient thiadiazine-containing OPV devices. The coupling chemistry of this system will be explored in future studies.

3. Materials and Methods

The reaction mixture was monitored by TLC using commercial glass-backed thin layer chromatography (TLC) plates (Merck Kieselgel 60 F₂₅₄). The plates were observed under UV light at 254 and 365 nm. The melting point was determined using a TA Instruments DSC Q1000 (TA instruments, New Castle, DE, USA) with samples hermetically sealed in aluminum pans under an argon atmosphere, using a heating rate of 5 °C/min (DSC mp listed by onset and peak values). The solvent used for recrystallization is indicated after the melting point. The UV-vis spectrum was obtained using a Perkin-Elmer Lambda-25 UV/vis spectrophotometer (Perkin-Elmer, Waltham, MA, USA) and inflections are identified by the abbreviation “inf”. The IR spectrum was recorded on a Shimadzu FTIR-NIR Prestige-21 spectrometer (Shimadzu, Kyoto, Japan) with Pike Miracle Ge ATR accessory (Pike Miracle, Madison, WI, USA) and strong, medium and weak peaks are represented by s, m and w, respectively. ¹H and ¹³C NMR spectra were recorded on a Bruker Avance 500 machine [at 500 and 125 MHz, respectively, (Bruker, Billerica, MA, USA)]. Deuterated solvents were used for homonuclear lock, and the signals are referenced to the deuterated solvent peaks. Attached proton test (APT) NMR studies were used for the assignment of the ¹³C peaks as CH₃, CH₂, CH and Cq (quaternary). The MALDI-TOF mass spectrum (+ve mode) was recorded on a Bruker Autoflex III Smartbeam instrument (Bruker). The elemental analysis was run by the London Metropolitan University Elemental Analysis Service. For the X-ray crystallography, each crystal was coated in paraffin oil and mounted on a Molecular Dimensions Litholoop and placed directly into the cold stream of the Bruker D8 Venture diffractometer (Bruker, Billerica, MA, USA). Single crystal X-ray diffraction data were collected using a Cu-Kα (λ = 1.5418 Å) on XtaLAB Synergy, Single source at home/near, HyPix diffractometer (Rigaku, Tokyo, Japan) using Bruker’s APEX3 program suite [17], with the crystal kept at 180.0 K during data collection. The structures were solved using Olex2 [18], with the olex2.solve [19] structure solution program using Charge Flipping and refined with the SHELXL [20] refinement package using Least Squares minimization. 2-[3,5-Di(thien-2-yl)-4H-1,2,6-thiadiazin-4-ylidene]-malononitrile (3) [21] was prepared according to the procedure in the literature.

2-[3,5-Bis(5-bromothien-2-yl)-4H-1,2,6-thiadiazin-4-ylidene]-malononitrile (4)

To a stirred mixture of 2-[3,5-di(thien-2-yl)-4H-1,2,6-thiadiazin-4-ylidene]-malononitrile (3) (32.6 mg, 0.100 mmol) in THF (2 mL) at ca. 20 °C was added N-bromosuccinimide (178 mg, 1.00 mmol) and the mixture stirred at this temperature until no starting material remained (TLC, 24 h). The mixture was then adsorbed onto silica and chromatographed (n-hexane/CH₂Cl₂, 60:40) to give the title compound 4 (39.6 mg, 82%) as orange needles, mp (DSC) onset 71.6 °C, peak max 72.7 °C (from EtOH); R_f 0.29 (n-hexane/CH₂Cl₂, 60:40); (found: C, 34.67; H, 0.78; N, 11.69. C₁₄H₄Br₂N₄S₃ requires C, 34.73; H, 0.83; N, 11.57%); λ_max (CH₂Cl₂)/nm 270 (log ε 3.14), 295 (3.23), 326 inf (3.12), 483 (3.25); ν_max/cm⁻¹ 3109 w (C-H), 2216 m (C≡N), 1526 m, 1501 m, 1454 m, 1433 m, 1414 s, 1344 m, 1321 m, 1283 w, 1219 w, 1209 w, 1109 w, 1027 w, 972 m, 966 m, 898 m, 820 m, 812 m, 800 m, 792 m, 741 m; δ_H (500 MHz; CDCl₃) 7.27 (2H, d, J 4.1, Thienyl H), 7.13 (2H, d, J 4.1, Thienyl H); δ_C (125 MHz; CDCl₃) 141.2 (Cq), 140.2 (Cq), 139.1 (Cq), 130.9 (CH), 129.7 (CH), 121.6 (Cq), 111.6 (Cq), 78.7 (Cq); m/z (MALDI-TOF) 486 (M⁺ + 4, 62%), 484 (M⁺ + 2, 100), 482 (M⁺, 48), 207 (36), 205 (31), 181 (91), 153 (51).