Chalcogen bonding interactions in chelating, chiral bis(selenocyanates)

Abstract

Introduction of methyl substituents on the achiral 1,2-bis(selenocyanatomethyl)benzene leads to a novel chelating ChB donor, namely 1,2-bis(1-selenocyanatoethyl)benzene (1), as a mixture of three diastereomers, the two anti enantiomers and the syn (meso) form. Structure determinations show the recurrent formation of short Se⋯N≡C ChB interactions in both the anti (racemic mixture) and syn isomers. Co-crystallization of anti-1 with 4,4′-bipyridine affords a 2 : 1 adduct, (anti-1)₂(bipy), with one very short Se⋯N_Py ChB (RR = 0.87). Co-crystallization of anti-1 with tetraphenylphosphonium halides (Cl⁻, Br⁻, I⁻) provides 1 : 1 adducts while a 2 : 1 adduct is isolated between syn-1 and Et₄NCl, formulated as Et₄N⁺[(syn-1)₂Cl⁻]. Comparison of chloride chelation with anti-1 and syn-1 shows much shorter (NC)Se⋯Cl⁻ ChB interactions with the syn isomer, tentatively rationalized on the basis of theoretical calculations of (i) the electrostatic surface potential of neutral ChB donors and (ii) the chloride BSSE complexation energy.

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Introduction

Non-covalent interactions¹ are currently developing as a cross-field area encompassing many different topics found in crystal engineering, anion recognition and transport, catalysis, biochemistry and material science. Following the huge development of halogen bonding (XB) in the last 25 years,² it became clear that elements of groups 14, 15 and 16 of the periodic table were also prone to exhibit electrophilic sites able to interact with a charge-concentrated area, in a way very similar to that shown by halogens where the development of an electron-deficient region (also called σ-hole)³ in the prolongation of the covalent bond to the halogen allows for strong and directional interactions with Lewis bases. These newcomers to the fields, described as tetrel (TrB),⁴ pnictogen (PnB)⁵ and chalcogen bonds (ChB),⁶ albeit much less developed than XB, present some specificities and offer new possibilities particularly on the field of supramolecular self-assembly and crystal engineering,^6a,7 catalysis,⁸ anion recognition⁹ and transport,¹⁰ and biochemistry.¹¹ If we focus on ChB, one main difference with XB is the presence, on the chalcogen atom when properly activated, of not one but two electron-depleted regions, located approximately in the extension of the two covalent bonds to the chalcogen.^3,12,13 This added element of complexity has several important structural implications such as: (i) possible deviations between the C_i–Ch and Ch⋯X (X = Lewis base) axes, and (ii) possibility for dissymmetry of chalcogen substitution implying a dissymmetry of the two σ-hole area. As a consequence, the very strong predictability of XB interactions finds in the analogous ChB systems some limitations, which have hampered its extensive use in crystal engineering strategies. Several prominent examples have however successfully overcome these problems, such as the self-assembly of 1,2-tellurazole 2-oxides into a variety of supramolecular aggregates,¹⁴ the use of bis-(selenophene/tellurophene) derivatives as chelating systems toward anions (Scheme 1a),^10,15,16 or double chalcogen bonding interactions exhibited by benzo-1,3-chalcogenazoles¹⁷ or chalcogenadiazoles.¹⁸

Scheme 1 (a) Structures of reported ChB donors chelating halides. (b) Systems with strongly asymmetric selenium activation (c) Organic selenocyanates: Sigma-holes and solid-state association.

Along these lines, one attempt to restore in ChB systems the strong directionality offered by halogens consists in functionalizing the chalcogen atom with only one strong electron-withdrawing substituent, as for example in rotaxanes incorporating selenomethyltriazolium moieties,¹⁹ in selenomethyl- or telluromethyl-acetylenes,²⁰ in icosahedral ortho-carboranes substituted with two methylseleno or methyltelluro groups (Scheme 1b),²¹ or in selenocyanate derivatives R–SeCN (Scheme 1c).^22,23 In such compounds, the electron-withdrawing character of the nitrile substituents strongly activates one of the two σ-holes, in the prolongation of the NC–Se bond, allowing to recover the predictability of interaction with Lewis bases. Indeed, selenocyanates themselves most often crystalize into chains ⋯NC–(R)Se⋯NC–(R)Se⋯ where the lone pair of the nitrogen atom of the nitrile interacts through ChB with the selenium atom showing Se⋯N distances around 3.0 Å, that is a reduction ratio RR (defined as the actual interatomic distance over the sum of the van der Waals radii) around 0.86. Recently, we reported several bis- or tetrakis-substituted selenocyanate derivatives such as A–D in Scheme 2a,²³ easily prepared from the corresponding benzylic bromides and KSeCN, which were shown to organize in the solid state with these recurrent chain-like motifs. These ChB interactions are notably enhanced when the selenocyanate is faced with stronger Lewis bases such as pyridines²⁴ or halide anions.²⁵ A remarkable feature of the ortho derivative A (or the 1,2,4,5-tetrakis derivative D) is its ability to chelate one single atom through the two selenium atoms, giving rise to seven-membered rings with either neutral (DMF) or anionic (halides) Lewis bases (Scheme 2b). These interactions were also confirmed in solution by ¹³C and ⁷⁷Se NMR.²⁶ With the ChB donors A and D, two specific conformations of the ortho-selenocyanatomethyl arms were observed on the solid state upon halide chelation, namely syn or anti, depending on the halide anion, its coordination number and the associated counter ion, without possibility to evaluate the relative stability of both conformations. In order to clarify this point and possibly favor one over the other conformation in these halide recognition processes, we designed an ortho bis(selenocyanate) derivative 1 analogous to A, but bearing an extra methyl group on each benzylic bridge (Scheme 2c). Compound 1 does thus exist as three diastereomers, the two anti enantiomers and the syn (meso) form. We describe here its synthesis, separation of the anti and syn forms and their association with neutral (4,4′-bipyridine) and charged (halide anion) Lewis bases. This novel ChB donor provides also a rare example of introduction of chirality in chalcogen-bonded systems.²⁷ Indeed, only a few examples of selenylation reagents were reported where an intramolecular Se⋯N or Se⋯O interaction rigidifies the chiral reagent and thus allows for stereochemical control,^6c,28 while recently a planar chiral ferrocenyl plateform was functionalized with iodomethyl- and selenomethyl-ethynyl moieties²⁹ for evaluation in the Ritter reaction.³⁰

Scheme 2 Benzylic selenocyanates and their halide chelates.

Results and discussion

Syntheses

The preparation of 1 is based on the nucleophilic substitution of 1,2-bis(1-bromoethyl)benzene 2 with KSeCN (Scheme 3). The preparation of 2 from reaction of 1,2-diethylbenzene with NBS has been reported to afford a diastereoisomeric mixture in a 3 : 1 ratio.³¹ Recrystallization was reported to yield a crystalline material composed essentially of the majority compound, whose stereochemistry was not assigned at that time. Based on the product obtained from the majority dibromo compound when reacted with glycine,³² the main diastereoisomer was later shown to be the anti one.

Scheme 3 Synthetic path to 1.

We have performed the bromination reaction of 1,2-diethylbenzene in the same conditions and isolated indeed a 70 : 30 anti-syn mixture. Recrystallization from hexane afforded the pure anti isomer whose stereochemistry was confirmed here by single crystal X-ray diffraction. Concentration of the mother liquors gives a 23 : 77 anti-syn mixture based on NMR. The dibromo derivative anti-2 crystallizes in the monoclinic system, S. G. P2₁/n, with one molecule in general position (Fig. 1a). No short intermolecular Br⋯Br interactions are identified. Nucleophilic substitution with KSeCN was not stereochemically conservative and afforded a mixture of anti- and syn-1, in 3 : 1 ratio when performed from pure anti-2. Recrystallization from acetone allowed to isolate anti-1 in a pure form. It crystallizes in the monoclinic system, S. G. P2₁/a, with one molecule in general position (Fig. 1b) showing one of the SeCN moieties disordered over two positions with 60 : 40 refined occupancy. From the concentrated mother liquors, some crystals of syn-1 were isolated with difficulties after hexane diffusion. The syn isomer was found to crystallize in the monoclinic system, S. G. P2₁/c, with one molecule in general position (Fig. 1c).

Fig. 1 Detail of the molecular structures of (a) anti-2, (b) anti-1, (c) syn-1.

The solid-state organization of anti-1 exhibits characteristic ChB interactions found in organic selenocyanates. As shown in Fig. 2, selenium atom Se1 acts as a twofold ChB donor, through its two σ-holes, with one very short interaction (RR = 0.86) in the prolongation of the NC–Se(1) bond, toward N2A(−x, −y, −z), and one longer contact (RR = 0.93) in the prolongation of the CH₂–Se(1) bond toward N1(−0.5 + x, 0.5 − y, z). On the other hand, selenium atom Se2 in not engaged at all in such a Se⋯N ChB but makes an inversion-centered Se(2A)⋯Se(2A) motif (3.391(6) Å, RR = 0.89) analogous to the so-called type I halogen-bonded motifs found in halogenated molecules. This complex behavior contrasts with that found for the less-substituted achiral derivatives such as the bis(selenocyanato) o-, m-, p-xylylenes where ⋯NC–Se(R)⋯⋯NC–Se(R)⋯ chains are systematically observed. It probably comes as a consequence of the steric constraint brought by the two extra methyl substituents in anti-1. The situation is different in syn-1. As shown in Fig. 3, each of the two selenium atoms acts here as ChB donor toward the nitrogen atom of the selenocyanate of neighboring molecules, giving the recurrent chains mentioned above, with however larger intermolecular distances (RR = 0.89, 0.95) and poorer linearity (the NC–Se⋯N angles here are only 162 and 127°).

Fig. 2 Details of the ChB interactions in anti-1. Only the major component of the disordered SeCN group is shown. Relevant bond distances and angles: Se(1)⋯N(2A)ⁱ: 2.978(25) Å, C(9)–Se(1)⋯N(2)ⁱ: 172.7(5)°; Se(1)–N(1)ⁱⁱ: 3.217(3) Å, C(7)–Se(1)⋯N(1)ⁱⁱ: 167.9(8)° (i: −x, −y, −z; ii: −0.5 + x, 0.5−y, z).

Fig. 3 Details of the ChB interactions in syn-1. Relevant bond distances and angles: Se(1)⋯N(2)ⁱ: 3.283(7) Å, C(9)–Se(1)⋯N(2)ⁱ: 162.6(2)°; Se(2)⋯N(1)ⁱⁱ: 3.074(7) Å, C(12)–Se(2)–N(1): 127.05(25)° (i: 1−x, −1−y, 1−z; ii: 1−x, −0.5+y, 0.5−z).

Co-crystal formation with anti-1 was investigated with both neutral Lewis bases such as 4,4′-bipyridine and anionic halide salts such as Ph₄PX (X = Cl⁻, Br⁻, I⁻). With 4,4′-bipyridine, co-crystallization afforded a chalcogen-bonded structure of 2 : 1 stoichiometry formulated as (anti-1)₂(bipy). It crystallizes in the monoclinic system, S. G. P2₁/a, with the 4,4′-bipyridine lying on an inversion center while linking the inversion-related enantiomers of anti-1 (Fig. 4). Both selenium atoms act here as ChB donors toward the pyridinic nitrogen atom, with one very short ChB, for Se(1)⋯N(3) (RR = 0.87) whereas the Se(2)⋯N(3) interaction is essentially a van der Waals contact distance, with a marked directionality for both interactions as the NC–Se⋯N(3) angles amount to 173.62(13) and 168.66(11)° respectively. Besides, the Se2 selenium atom acts as a ChB donor in a Se(2)⋯N(2) contact through its second weaker σ-hole located in the prolongation of the CH₂–Se bond, while Se(1) forms an inversion-centered Type I Se⋯Se motif. Note that the co-crystals formed from 4,4’-bipyridine and the unsubstituted meta- or para- bis(selenocyanato)xylylenes are characterized with notably stronger Se⋯N ChB interactions, with RR values in the range 0.82–0.84.^24a

Fig. 4 Detail of the trimolecular adduct between anti-1 and 4,4′-bipyridine. The strongest interaction is highlighted with a thicker dotted line. Relevant bond distances and angles: Se(1)⋯N(3): 3.003(4) Å, C(9)–Se(1)⋯N(3): 173.62(13)°; Se(2)⋯N(3): 3.481(3) Å, C(12)–Se(2)⋯N(3): 168.66(11)°; Se(2)⋯N(2)ⁱ: 3.198(3) Å, C(11)⋯Se(2)⋯N(2)ⁱ: 141.06(8)°; Se(1)⋯Se(1)ⁱⁱ: 3.667(1) (i: 0.5+x, 0.5−y, z; ii: −x, −y, 2−z).

Co-crystals of anti-1 with the three tetraphenyl phosphonium halides, i.e. Ph₄PCl, Ph₄PBr and Ph₄PI, all crystallize in a 1 : 1 stoichiometry with the halide in a μ₂ environment, chelated by the ditopic ChB donor. The chloride and bromide salts are isostructural, and crystallize with Et₂O solvate in the triclinic system, space group P1, with the anionic complex in general position. As shown in Fig. 5a and b, the environment of the Cl⁻ and Br⁻ anions is asymmetric with one (NC)–Se⋯X⁻ ChB slightly shorter than the other. In both cases, the overall Se⋯X⁻ distance corresponds to a reduction ratio (considering the ionic radius of the halide rather than the van der Waals radius of the neutral atom, i.e. Cl⁻: 1.81 Å, Br⁻: 1.96 Å, I⁻: 2.20 Å) in the range 0.88–0.90. These values are notably larger than those reported earlier in the unsubstituted achiral analogs chelating Cl⁻ or Br⁻ anions, which exhibit RR values as small as 0.84.²⁵

Fig. 5 Detail of the three halide adducts with structural characteristics in: (a) Ph₄P⁺[(anti-1)Cl⁻]·(Et₂O)_0.5, (b) Ph₄P⁺[(anti-1)Br⁻]·(Et₂O)_0.5,and (c) Ph₄P⁺[(anti-1)I⁻]. Relevant bond distances and angles: Se(1)⋯Cl: 3.330(7) Å, (N)C–Se(1)⋯Cl: 173.75(13)°, Se(2)⋯Cl: 3.262(6) Å, (N)C–Se2⋯Cl: 173.67(13)°; Se(1)⋯Br: 3.436(4) Å, (N)C–Se(1)⋯Br: 175.12(13)°, Se(2)⋯Br: 3.383(3) Å, (N)C–Se2⋯Br: 174.48(13)°; Se(1)⋯I: 3.603(1) Å, (N)C–Se(1)⋯I: 177.6(2)°, Se(2)⋯I: 3.670(1) Å, (N)C–Se(2)⋯I: 167.8(2)°.

The situation is more complex in the iodide adduct (Fig. 5c). It crystallizes without solvent in the orthorhombic system, space group P2₁2₁2₁, with the anionic complex in general position. The Se⋯I⁻ distances are here associated with RR values of 0.88–0.89 and one (N)C–Se⋯I− angle deviates notably from 180° (167°).

These three structures and the relatively long Se⋯X⁻ distances seem to indicate that the introduction of the methyl substituents on the benzylic positions induces, in the anti-isomer at least, an unfavorable effect on the ChB donor ability of this chelating system. At first sight, this effect might have two origins, (i) the electron-donating effect of the methyl groups might decrease the overall ChB donor ability of the selenium atoms, and/or (ii) the steric constraints brought by the methyl groups do not favor the optimal “coordination” of the halide anion, at least in the anti conformation of the chelate.

One first element of answer can be already found in the crystal structure obtained from the association of Et₄NCl and the syn isomer, using a syn-enriched sample. A 2 : 1 association formulated as (Et₄N⁺)[(syn-1)₂Cl⁻] is indeed isolated, which crystallizes in the monoclinic system, space group P2₁/a, with the Cl⁻ anion lying on an inversion center in a μ₄ square-planar environment (Fig. 6). The Se⋯Cl⁻ distances are very short (3.11–3.16 Å, RR = 0.84-0.85), even shorter than those reported in the chloride adduct of the achiral chelating ortho-bis(selenocyanate)xylylene A (3.17–3.20 Å, RR = 0.85-0.86) or the 1,2,4,5-tetrakis(selenocyanoatomethyl)benzene E (3.16–3.22 Å, RR = 0.85-0.87).²⁵

Fig. 6 Detail of the anionic moiety [(syn-1)₂Cl⁻] in its Et₄N⁺ salt. Relevant bond distances and angles: Se(1)⋯Cl: 3.108(3) Å, C–Se(1)⋯Cl: 176.2(2)°; Se(2)⋯Cl: 3.160(1) Å, C–Se(2)⋯Cl: 176.0(3)°.

In order to rationalize these differences, theoretical calculations of the relative energies of the molecules (anti vs. syn) and their Cl⁻ adducts were performed. The total energy was calculated for the syn and anti forms of 1 [B3LYP 6-311++G(d,p)] after geometry optimization, keeping the C₂ geometry for the anti form, and the C_s geometry for the syn form (Fig. 7). Under these conditions, the anti form is more stable by 2.31 kcal mol⁻¹ (9.7 kJ mol⁻¹) than the syn form. Without symmetry constraints, the syn form is able to find a more stable conformation through an intramolecular Se⋯Se ChB interaction (3.958 Å), reducing the difference to 0.68 kcal mol⁻¹ (2.8 kJ mol⁻¹).

Fig. 7 Optimized geometries of anti-1 and syn-1 with and without symmetry constraints.

The evolution of the σ-hole amplitude has been determined for three molecules, bearing either a methyl group on each benzylic carbon (that is in anti-1 and syn-1) or a hydrogen atom (that is the unsubstituted molecule A in Scheme 1) or, for comparison purposes, a fluorine atom (instead of a methyl group) in the fluorine-substituted derivatives of A (that is anti-3 and syn-3). As shown in Fig. 8a, we note a very small difference between anti-1 and syn-1, with V_s,max values of 46.26 and 47.05 kcal mol⁻¹ respectively, i.e. a slightly larger V_s,max value for syn-1. Such a small difference cannot explain the much shorter ChB interaction experienced with the Cl⁻ anion with syn-1 (see above). The evolution in the series of substituents Me₂/H₂/F₂ follows the expected trend, with a strengthening of the V_s,max in the order F₂ > H₂ > Me₂ associated with the electron withdrawing effect of the fluorine atoms. Furthermore, an even stronger electropositive area (54.3 kcal mol⁻¹) is identified in the fluorine substituted syn-3 in-between the two activated benzylic hydrogen atoms located in α position with respect to the fluorine atoms. These calculations demonstrate that, whatever the substituents, the syn form exhibits systematically a slightly stronger σ-hole than the anti form. However, they are unable to explain the much shorter ChB interaction with Cl⁻.

Fig. 8 Details of the ESP maps of (a) methyl-substituted anti-1 and syn-1, (b) unsubstituted A and (c) fluorine-substituted anti-3 and syn-3, at optimized geometries, plotted on the 0.001 a.u. isosurface of the electronic density. The extrema values V_s,max (kcal mol⁻¹) of the electropositive (blue) area are indicated in red numbers. Potential scale ranges from −25.1 kcal mol⁻¹ (red) to +37.7 kcal mol⁻¹.

Calculations performed on 1 : 1 adducts with the syn and anti forms of 1 and a chloride anion give geometries very close to those observed in the crystal structures of Ph₄P⁺[(anti-1)Cl⁻]·(Et₂O)_0.5 and Et₄N⁺[(syn-1)₂Cl⁻] (Fig. 9). The notably shorter Se⋯Cl⁻ distances with syn-1 (3.11-3.16 Å, vs. 3.26-3.33 Å with anti-1) is very well reproduced by the calculations, which give a Se⋯Cl⁻ distance of 3.139 Å in the syn-1·Cl⁻ adduct (C_s geometry) that is notably smaller than the 3.210 Å distance calculated in anti-1·Cl⁻ adduct (C₂ geometry). The overall energy is very similar in both adducts ΔG(syn-1·Cl⁻ − anti-1·Cl⁻) = 1.29 kcal mol⁻¹, being slightly more stable with anti- adducr 1. On the other hand, the BSSE complexation energy (−35.36 kcal mol⁻¹ for anti-1·Cl⁻, −35.55 kcal mol⁻¹ for syn-1·Cl⁻) gives a small advantage to the syn adduct. It appears therefore that the shorter Se⋯Cl⁻ ChB interaction experienced with the syn-1 ChB donor is not associated with a sizeable stabilization of this chloride adduct, when compared with its anti analog. As shown in Fig. 8, the electropositive area (in blue) interacting with Cl⁻ exceeds that delineated with the selenium atoms only and include also the two benzylic hydrogen atoms. The overall interactions in both adducts thus implies also C_Bz–H⋯Cl⁻ contacts, whose geometrical features (for both experimental and calculated structures) are collected in Table 1. These contacts are quite short (2.79-2.86 Å vs. a van der Waals contact distance of 3.01 Å) even if they deviate notably from linearity (C–H⋯Cl⁻ angles in the range 123–128°). Their contribution to the overall stabilization of the adducts can probably not be omitted.

Fig. 9 Optimized geometries of the anti-1·Cl⁻ and syn-1·Cl⁻ adducts with indicated symmetry constraints.

Table 1 Structural characteristics of C–H⋯Cl⁻ contacts, from X-ray crystal structures of Ph₄P⁺[(anti-1)Cl⁻]·(Et₂O)_0.5 and Et₄N⁺[(syn-1)₂Cl⁻] and from theoretical calculations on 1 : 1 adducts (in italics)

		H⋯Cl^− dist (Å)	C–H⋯Cl– ang. (°)
(anti-1)Cl^−	X-ray	2.863(6)	128.1(2)
		2.800(4)	127.0(2)
	Calcd.	2.522	138.1
(syn-1)Cl^−	X-ray	2.794(2)	125.2(3)
		2.811(2)	123.0(4)
	Calcd.	2.573	134.9

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Conclusions

Introduction of methyl substituents on the achiral 1,2-bis(selenocyanatomethyl)benzene (A) leads to diastereoisomers of a novel chelating, chiral ChB donor, namely 1,2-bis(1-selenocyanatoethyl)benzene (1), as a mixture of the two anti enantiomers and the syn (meso) form. The anti (racemic) mixture was isolated in a pure form by recrystallization. We were able to isolate crystals of both anti-1 and syn-1. Structure determinations show the recurrent formation of short Se⋯N≡C ChB interactions (RR = 0.88-0.95). Co-crystallization of anti-1 with 4,4’-bipyridine affords a 2 : 1 adduct, i.e. (anti-1)₂(bipy), with one very short Se⋯N_Py ChB at 3.003 Å (RR = 0.87). Co-crystallization of anti-1 with tetraphenylphosphonium halides (Cl⁻, Br⁻, I⁻) provides the 1 : 1 adducts, while a 2 : 1 adduct is isolated between syn-1 and Et₄NCl, formulated as Et₄N⁺[(syn-1)₂Cl⁻]. Comparison of chloride chelation with anti-1 and syn-1 shows much shorter (NC)Se⋯Cl⁻ ChB interactions with the syn isomer. Calculations of (i) the electrostatic surface potential of neutral ChB donors for σ-hole amplitude determination and (ii) the Cl⁻ BSSE complexation energy, cannot explain these differences even if the geometry optimizations well reproduce them. Besides, the concomitant contribution of C–H⋯Cl⁻ hydrogen bonds involving benzylic hydrogen atoms α to the SeCN moieties is highlighted. Altogether, the notably shorter Se⋯Cl⁻ distances found with the syn isomer appear to be a mere consequence of the overall relative orientation of both selenocyanate moieties together with contribution of C_Bz–H⋯Cl⁻ hydrogen bonds, as illustrated by the broader spatial expansion of the electropositive area observed in the syn isomer. This modulation of the ChB donor ability, combined with the introduction of chirality, provides novel chelating ChB donors which will be of interest in crystal engineering, anion recognition processes and catalysis. We are pursuing our works along these lines.

Experimental section

General remarks

NMR spectra were recorded at room temperature using CDCl₃ unless otherwise noted. Chemical shifts are reported in ppm and ¹H NMR spectra were referenced to residual CHCl₃ (7.26 ppm) and ¹³C NMR spectra were referenced to CHCl₃ (77.2 ppm). All reagents are commercially available and were used without further purification. Melting points were measured on a Kofler hot-stage apparatus and are uncorrected. Elemental analysis were performed at BioCIS laboratory, UMR-8076-CNRS-University Paris-Saclay. All the reactions were performed under an argon atmosphere. Methanol, acetonitrile and dichloromethane were dried using inert pure solvent column device.

Syntheses

1,2-Bis(1-bromoethyl)benzene 2. In a 100 mL two-neck round-bottom flask equipped with condenser, 1,2-diethylbenzene (2 g, 14.9 mmol) and NBS (5.3 g, 29 mmol, 2 eq.) are dissolved in CCl₄ (30 mL) and warmed to reflux. After addition of a little AIBN, stirring is maintained for 30 minutes. Another small quantity of AIBN is added again. After an hour of stirring and cooling, the succinimide is eliminated by filtration. The filtrate is evaporated and the solid residue filtered through a silica column with petroleum ether as eluant. Evaporation of the solvent yields 2 as a white solid (2.93 g, 67%), in a ratio anti/syn of 70 : 30 (based on ¹H NMR). Pure anti-2 is obtained by recrystallization in hexane, while the mother liquors are enriched in syn isomer in a ratio anti/syn of 23 : 77.

anti-2 m.p. 89 °C. ¹ H NMR (300 MHz, CDCl₃) δ 2.15 (6H, d, J³ = 6.84 Hz); 5.71 (2H, q, J³ = 6.84); 7.34–7.40 (2H, m); 7.58–7.63 (2H, m)

syn-2¹ H NMR (300 MHz, CDCl₃) δ 2.10 (6H, d, J³ =6.90 Hz); 5.61 (2H, q, J³ = 6.90); 7.32-7.38 (2H, m); 7.58-7.63 (2H, m).

1,2-Bis(1-selenocyanatoethyl)benzene 1. To a solution of anti-2 (0.59 g, 2 mmol) dissolved in acetone (5 mL) at room temperature, KSeCN (0.87 g, 6 mmol, 3 eq.) dissolved in warm acetone (5 mL) is added dropwise over a period of 10 minutes. After 30 minutes of stirring, the suspension is filtered, the filtrate is evaporated, and the resulting solid dissolved in CH₂Cl₂ (10 mL) and washed with water (2 × 10 mL). The organic layers are collected, dried with MgSO₄, filtered and evaporated to give 1 (0.59 g, 86%) as a white solid in a ratio anti/syn of 76 : 24 (based on NMR). Pure sample of anti-1 is obtained from recrystallization in acetone. The same reaction performed with 2 in a anti/syn ratio of 23 : 77 afforded 1 in a anti/syn ratio of 66 : 34.

anti-1. M. p. 113 °C; ¹ H NMR (300 MHz, CDCl₃) δ 2.12 (6H, d, J³ = 6.9 Hz); 5.25 (2H, q, J³ = 6.9); 7.40–7.45 (2H, m); 7.54–7.59 (2H, m). ¹³C NMR: 22.58 (CH₃); 40.00 (C̲H–CH₃); 101.86; 127.24; 129.65, 137.06. Elem. Anal calcd for C₁₂H₁₂N₂Se₂: C, 42.12; H, 3.54; N, 8.19; found: C, 41.92; H, 3.57; N, 8.20. Mother liquors are enriched in syn compound with a syn : anti distribution of 67 : 33. Their dissolution in acetone and diffusion of hexane afforded a few crystals of syn-1 suitable for X-ray diffraction. syn-1: ¹H NMR (300 MHz, CDCl₃) δ 2.15 (6H, d, J³ = 6.90 Hz); 5.17 (2H, q, J³ = 6.90); 7.40–7.45 (2H, m); 7.54–7.59 (2H, m). ¹³C NMR: 24.03 (CH₃); 40.11 (C̲H-CH₃); 101.97; 127.58; 129.69, 136.84.

(anti-1)₂(4,4′-bipy). In a small test tube, 4,4’-bipyridine (10 mg, 0.06 mmol) and anti-1 (11 mg, 0.03 mmol) are dissolved in acetone (1 mL). Diffusion of Et₂O vapors affords after 5 days colorless crystals of (anti-1)₂(4,4’-bipy). Elem. anal. calcd for C₃₄H₃₂N₆Se₄: C, 48.59; H, 3.84; N, 10.00; found: C, 48.57; H, 3.91; N, 9.95.

Ph₄PCl(anti-1)·(Et₂O)_0.5. In a small tube, anti-1 (11 mg, 0.03 mmol) and Ph₄PCl (13.5 mg, 0.036 mmol), were dissolved in acetonitrile (1 mL). The tube was placed into a small bottle with ether for diffusion crystallization. Crystals were isolated after 5 days. Exact composition was deduced from X-ray diffraction. Elem. anal. calc. for C₃₆H₃₂ClN₂PSe₂ (without Et₂O): C, 60.3; H, 4.5; N, 3.91; found: C, 56.21; H, 4.62; N, 4.20.

Ph₄PBr(anti-1)·(Et₂O)_0.5. In a small tube, anti-1 (10 mg, 0.03 mmol) and Ph₄PBr (17.7 mg, 0.042 mmol) were dissolved in 1 mL of acetonitrile. The tube was placed into a small bottle with ether for diffusion crystallization. Crystals were isolated after 5 days. Exact composition was deduced from X-ray diffraction. Elem. anal. calcd for C₃₆H₃₂BrN₂PSe₂ (without Et₂O): C, 56.78; H, 4.24; N, 3.68; found: C, 56.98; H, 4.71; N, 2.34.

Ph₄PI(anti-1). In a small tube, anti-1 (13 mg, 0.04 mmol, 1 equiv.) and Ph₄PI (21 mg, 0.045 mmol, 1 equiv.) were dissolved in 1 mL of acetonitrile. The tube was put into a small bottle with ether for diffusion crystallization. Crystals were isolated after 5 days. Elem. anal. calcd for C₃₆H₃₂IN₂PSe₂: C, 53.48; H, 3.99; N, 3.47; found: C, 54.43; H, 4.02; N, 3.42.

Et₄NCl(syn-1)₂. In a small tube, a 67/33 mixture of syn-1/anti-1 (10 mg, 0.03 mmol) and Et₄NCl (4.9 mg, 0.03 mmol) were dissolved in acetone (1 mL). The tube was placed into a small closed bottle with hexane for diffusion crystallization. Crystals were isolated after 5 days. Elem. anal. calcd for C₃₂H₄₄ClN₅Se₄: C, 45.22; H, 5.22; N, 8.24; found: C, 44.88; H, 6.13; N, 7.97.

Crystallography. Details of the structural analyses for the eight compounds are summarized in Table 2. Single crystals were coated with Paratone-N oil and mounted on a MicroMount loop. The crystallographic data were collected at 296(2)K on a Bruker AXS APEX II diffractometer with Mo-Kα radiation (λ = 0.71073 Å) for all compounds except anti-1 and anti-2 which were collected on a Bruker AXS D8 Venture diffractometer equipped with a Mo-Kα microsource and a PHOTON 100 detector at 150(2) K. The structures were solved by dual-space algorithm using SHELXT programs³³ and then refined with full-matrix least-squares methods based on F² (SHELXL-2014)³⁴ with the aid of the WinGX program.³⁵ All non-hydrogen atoms were refined with anisotropic atomic displacement parameters. Crystallographic data have been deposited with Cambridge Crystallographic Data Centre, CCDC: 2040289-2040296.†

Table 2 Crystallographic data

Compound	anti-1	syn-1	anti-2	(anti-1)2·bipy
Formula	C12H12N2Se2	C12H12N2Se2	C10H12Br2	C17H16N3Se2
FW (g mol^−1)	342.16	342.16	292.02	420.25
Crystal system	Monoclinic	Monoclinic	Monoclinic	Monoclinic
Space group	P21/a	P21/n	P21/n	P21/a
a (Å)	7.5686(4)	8.5502(6)	8.2203(8)	7.1221(4)
b (Å)	21.7486(11)	7.0090(4)	14.6643(16)	28.6165(13)
c (Å)	8.2075(4)	22.6261(15)	9.4380(9)	8.6600(5)
α (°)	90.00	90.00	90.00	90.00
β (°)	105.783(2)	90.121(3)	110.312(3)	105.763(2)
γ (°)	90.00	90.00	90.00	90.00
V (Å^3)	1300.07(11)	1355.94(15)	1066.96(19)	1698.62(16)
T (K)	150(2)	296(2)	150(2)	296(2)
Cryst. dim. (mm^3)	0.16 × 0.12 × 0.05	0.23 × 0.17 × 0.02	0.12 × 0.09 × 0.02	0.26 × 0.21 × 0.18
Z	4	4	4	4
D calc (g cm^−3)	1.748	1.676	1.818	1.643
μ (mm^−1)	5.663	5.429	7.544	4.353
Abs. corr.	Multi-scan	Multi-scan	Multi-scan	Multi-scan
T min, Tmax	0.447, 0.753	0.344, 0.897	0.447, 0.860	0.347, 0.457
Total refls.	20013	22207	19035	12513
Uniq. refls. (Rint)	2993 (0.0572)	3062 (0.0753)	2439 (0.0571)	3912 (0.0291)
Unique refls.	2631	1862	1943	3041
(I > 2s(I))R1	0.027	0.0495	0.0220	0.0367
wR2 (all data)	0.066	0.1128	0.0513	0.0717
GoF	1.067	1.076	1.052	1.085
Res. dens (e Å^−3)	0.50, −0.65	0.41, −0.52	0.43, −0.78	0.39, −0.64

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Compound	Ph4PCl(anti-1) ·0.5 Et2O	Ph4PBr(anti-1) ·0.5 Et2O	Ph4PI(anti-1)	Et4NCl(syn-1)2
CCDC
Formula	C38H37ClN2O0.50PSe2	C38H37BrN2O0.50PSe2	C36H32IN2PSe2	C16H22Cl0.50N2.50Se2
FW (g mol^−1)	754.03	798.49	808.42	425
Crystal system	Triclinic	Triclinic	Orthorhombic	Monoclinic
Space group	P1̄	P1̄	P212121	P21/c
a (Å)	9.2775(11)	9.3752(5)	9.2747(2)	9.0534(5)
b (Å)	13.5469(16)	13.5967(6)	10.6749(2)	13.1176(6)
c (Å)	14.3091(15)	14.3500(7)	34.3002(6)	16.4261(7)
α (°)	82.498(4)	82.051(2)	90.00	90.00
β (°)	88.218(4)	87.549(2)	90.00	112.672(2)
γ (°)	83.497(4)	83.173(2)	90.00	90.00
V (Å^3)	1771.3(4)	1798.15(15)	3395.94(11)	1800.00(15)
T (K)	296(2)	296(2)	296(2)	296(2)
Cryst. dim. (mm^3)	0.23 × 0.11 × 0.10	0.28 × 0.16 × 0.13	0.22 × 0.10 × 0.08	0.25 × 0.21 × 0.01
Z	2	2	4	4
D calc (g·cm^−3)	1.414	1.475	1.581	1.568
μ (mm^−1)	2.238	3.242	3.161	4.179
Abs. corr.	Multi-scan	Multi-scan	Multi-scan	Multi-scan
T min, Tmax	0.744, 0.799	0.542, 0.656	0.691, 0.777	0.366, 0.959
Total refls.	43521	29306	24731	4122
Uniq. refls. (Rint)	8141 (0.0375)	8249 (0.0298)	7781 (0.0247)	4121
Unique refls. (I > 2s(I))	5829	5578	6512	2069
R 1	0.0434	0.0371	0.0327	0.0624
wR 2 (all data)	0.1222	0.091	0.070	0.1591
GoF	1.142	1.059	1.02	1.027
Res. dens (e Å^−3)	0.652, −0.951	0.898, −0.596	0.557, −0.391	0.568, −0.561
Flack param.	—	—	0.64(1)	—

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Theoretical calculations

Theoretical calculations were performed using the Gaussian09 software³⁶ at the DFT level employing the B3LYP functional and the 6-311 + +G(d,p) basis set. Molecular structures of anti-1, syn-1, anti-A, syn-A, fluorine-substituted anti-3 and syn-3 were optimized and frequency calculations were performed in order to check that true energy minima were obtained. Electrostatic potential (ESP) mapped on the ρ = 0.001 a.u. isodensity surface were then computed with the AIMAll software package;³⁷ the maximum of ESP V_s,max in the region of the (NC)Se σ-holes associated with Se atoms were located with MultiWFN software.³⁸

Whereas anti-1 optimized under C₂ symmetry toward a true energy minimum, syn-1 optimized toward a C_s molecular structure associated with a small imaginary frequency (−20 cm⁻¹). Further optimization of that structure without symmetry constrain led to a true energy minimum characterized by an intramolecular Se⋯Se interaction [d(Se⋯Se) = 3.958 Å, RR = 1.04; α(C–Se⋯Se) = 154.6°)], with the (NC)Se σ-hole of one of the two selenium atoms pointing toward one lone pair of the second chalcogen atom. The C_s constrained syn-1 molecular structure is then reported for comparison purposes, since in that structure the two chalcogen (NC)Se σ-holes are oriented as in the halide adducts. The same situation occurs for syn-A which was calculated under constrained C_s symmetry (imaginary frequency = −12 cm⁻¹; the two σ-holes pointing outward the molecule) and also under C1 symmetry [intramolecular Se⋯Se interaction d(Se⋯Se) = 3.692 Å, RR = 0.97; α(C–Se⋯Se) = 169.4°]. For fluorine-substituted syn-3 molecule, the C_s symmetry constrained structure corresponds also to a saddle point (imaginary frequency = −9 cm⁻¹; the two σ-holes pointing outward the molecule) but the unconstrained C1 symmetry structure does not present the previously observed intramolecular Se⋯Se interaction due to an unfavorable relative NCSe orientations [d(Se⋯Se) = 4.044 Å, RR = 1.06; α(C–Se⋯Se) = 128.4°].

Molecular structures of the (anti-1)Cl⁻ and (syn-1)Cl⁻ were also optimized using the same calculation conditions and true energy minima were obtained. Basis Set Superposition Error corrected structures and complexation energies were obtained through the counterpoise method of Boys & Bernard.³⁹ More details are given in the Supporting Information file (Cartesian coordinates of optimized molecular structures).

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by the French National Agency for Research (ANR 17-CE07-0025-01 and ANR 17-CE07-0025-02. The EXPLOR mesocentre is thanked for computing facilities (Project 2019CPMXX0984).

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Footnote

† Electronic supplementary information (ESI) available: Computational details. CCDC 2040289–2040296. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d0nj05293k

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