molecules Article Polymorphism, Halogen Bonding, and Chalcogen Bonding in the Diiodine Adducts of 1,3- and 1,4-Dithiane Andrew J. Peloquin 1, Srikar Alapati 2, Colin D. McMillen 1, Timothy W. Hanks 2 and William T. Pennington 1,* 1 Department of Chemistry, Clemson University, Clemson, SC 29634, USA; [email protected] (A.J.P.); [email protected] (C.D.M.) 2 Department of Chemistry, Furman University, Greenville, SC 29613, USA; [email protected] (S.A.); [email protected] (T.W.H.) * Correspondence: [email protected] Abstract: Through variations in reaction solvent and stoichiometry, a series of S-diiodine adducts of 1,3- and 1,4-dithiane were isolated by direct reaction of the dithianes with molecular diiodine in solution. In the case of 1,3-dithiane, variations in reaction solvent yielded both the equatorial and the axial isomers of S-diiodo-1,3-dithiane, and their solution thermodynamics were further studied via DFT. Additionally, S,S’-bis(diiodo)-1,3-dithiane was also isolated. The 1:1 cocrystal, (1,4-dithiane)·(I2) was further isolated, as well as a new polymorph of S,S’-bis(diiodo)-1,4-dithiane. Each structure showed significant S···I halogen and chalcogen bonding interactions. Further, the product of the diiodine-promoted oxidative addition of acetone to 1,4-dithiane, as well as two new cocrystals of 1,4-dithiane-1,4-dioxide involving hydronium, bromide, and tribromide ions, was isolated. Keywords: crystal engineering; chalcogen bonding; halogen bonding; polymorphism; X-ray diffraction Citation: Peloquin, A.J.; Alapati, S.; McMillen, C.D.; Hanks, T.W.; Pennington, W.T. Polymorphism, Halogen Bonding, and Chalcogen Bonding in the Diiodine Adducts of 1. Introduction 1,3- and 1,4-Dithiane. Molecules 2021, Halogen bonding, and the related chalcogen bonding, interactions occur due to an inter- 26, 4985. https://doi.org/10.3390/ action between the electrophilic region on a halogen or chalcogen atom within a molecule and molecules26164985 a nucleophilic region on a different atom [1–4]. Due to their strength [5] and directionality [6], these interactions have emerged as useful tools in crystal engineering [7,8], pharmaceutical Academic Editors: Ryan Groeneman design [9–11], and in the understanding of synthetic transformations [12–14]. and Eric Reinheimer The reaction of diiodine, one of the simplest halogen bond donors, with thioethers allows the concomitant study of halogen and chalcogen bonding, as well as the competition Received: 26 July 2021 between the two. Several notable examples of reaction products from diiodine with cyclic Accepted: 12 August 2021 polythioethers exist in the literature, ranging from simple examples such as 1,4-dithaine [15] Published: 17 August 2021 and 1,3,5-trithiane [16] to larger macrocycles [17–19]. A common structural motif that emerges is the presence of an S···I halogen bond of varying strength, with a combination of Publisher’s Note: MDPI stays neutral halogen and chalcogen bonding to consolidate packing in the crystalline state. The charge with regard to jurisdictional claims in transfer component of these interactions has also been extensively characterized, with the published maps and institutional affil- interaction primarily attributed to an n!σ type interaction that increases in strength in the iations. order of O < S < Se [20–22]. Herein, we report the isolation of a variety of crystalline polymorphs from the reaction of 1,3- and 1,4-dithiane with diiodine. In the case of 1,3-dithiane, two geometric isomers of S-diiodo-1,3-dithiane were isolated, with their solution behavior further studied via Copyright: © 2021 by the authors. DFT computations, as well as S,S’-bis(diiodo)-1,3-dithiane. For 1,4-dithiane, the previously Licensee MDPI, Basel, Switzerland. reported 1:1 cocrystal with I2 was isolated [15,23], as well as a new polymorph of S,S’- This article is an open access article bis(diiodo)-1,4-dithiane. Each of these structures reveals an interplay between S···I halogen distributed under the terms and and chalcogen bonding. In the course of our investigations, we found that diiodine conditions of the Creative Commons Attribution (CC BY) license (https:// promoted oxidative addition of acetone to 1,4-dithiane, and we isolated two structures creativecommons.org/licenses/by/ from the direct oxidation of the compound to dioxides, revealing alternative reaction 4.0/). pathways in these halogen-containing systems. Molecules 2021, 26, 4985. https://doi.org/10.3390/molecules26164985 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x FOR PEER REVIEW 2 of 10 Molecules 2021, 26, 4985 2 of 10 oxidation of the compound to dioxides, revealing alternative reaction pathways in these halogen-containing systems. 2. Results and Discussion 2. Results and Discussion 2.1. Reaction of 1,3-Dithiane with I2 2.1. Reaction of 1,3-Dithiane with I2 While the product of the reaction of 1,4-dithiane and I2 was first reported in the literatureWhile in the 1960 product [15,23 of], the reaction analogous of 1,4 reaction-dithiane of 1,3-dithianeand I2 was first has reported not been in reportedthe litera- inture the in intervening 1960 [15,23] 6, the decades. analogous Through reaction variations of 1,3-dithiane in stoichiometry has not been and reported solvent in utilized the in- fortervening the reaction, 6 decades. we obtainedThrough threevariation distincts in stoichiometry products: S-diiodo-1,3-dithiane and solvent utilized infor both the reac- the equatorialtion, we obtained (1) and three axial distinct (2) orientation products: of S the-diiodo diiodo-1,3- pendant,dithiane in as both well the as equatorial S,S’-bis(diiodo)- (1) and 1,3-dithianeaxial (2) orientation (3) (Figures of the1 and diiodo2 and pendant, Figures as S10–S12). well as WhenS,S’-bis(diiodo) the reaction-1,3- wasdithiane conducted (3) (Fig- atures a 1:11 and stoichiometry 2). When the inreaction methanol, was conducted crystalline at1 a was1:1 stoichiometry obtained, with in methanol, the S-I-I crystalline group in a1 pseudo-equatorialwas obtained, with the position, S-I-I group with in an a pseudo angle of-equatorial 52.29(3)◦ position,between with I-I andan angle the RMSof 52.29(3) ring° planebetween (Table I-I and1). Thethe RMS position ring ofplane this (Table substituent 1). The significantly position of this deviates substit fromuent thesignificantly typical equatorialdeviates from position the typical (though equatorial not to the position degree (though of the axial not conformerto the degree2 described of the axial below). con- ◦ Forformer example, 2 described the analogous below). For angle example, for an equatorialthe analogous C-H angle in this for molecule an equatorial is only C 8.43(16)-H in this. Individualmolecule is moleculesonly 8.43(16) pack°. Individual in pairs in molecules the solid-state pack in via pa twoirs in C-H the ···solidS hydrogen-state via bondstwo C- (H···SdH···S hydrogen= 2.8840(17) bonds Å, R (d=H···S 0.93). = 2.8840(17) These crystallographicÅ, R = 0.93). These dimers crystallographic further interact dimers to further form sheetsinteract in to the formbc plane sheets by in anthe S bc··· Splane contact by an involving S···S contact an unsubstituted involving an unsubstituted sulfur atom on sulfur one ringatom and on one the ring diiodo-substituted and the diiodo-sub sulfurstituted atom sulfur on aatom neighboring on a neighboring ring (d Sring···S =(d 3.3571(6)S···S = 3.3571(6) Å, ◦ RÅ,= R 0.89 = ).0.89). Alternating Alternating dimers dimers are rotated are rotated by approximately by approximately 72 to 72 one° to another. one another. The sheets The stacksheets in stack the aindirection the a direction by a type by Ia halogentype I halogen interaction interaction between between terminal terminal iodine atomsiodine d ◦ (atomsI···I = ( 3.8019(3)dI···I = 3.8019(3) Å, qC-H Å,··· Sθ=C-H···S 128.64(15) = 128.64(15)). °). FigureFigure 1. 1.The The solid-statesolid-state structurestructure ofof1 1( a(a),),2 2( b(b),), and and3 3( c().c). Carbon Carbon atomsatoms areare gray.gray. Sulfur Sulfur atoms atoms areare yellow. yellow. Iodine Iodine atoms atoms areare purple. purple. HydrogenHydrogen atomsatoms are are cyan. cyan. IntermolecularIntermolecularinteractions interactionsare areshown shown as as black black dotted dotted lines. lines. OnlyOnly hydrogenhydrogen atoms atoms involved in the indicated intermolecular interactions are shown for clarity. Atomic displacement ellipsoids are shown at involved in the indicated intermolecular interactions are shown for clarity. Atomic displacement ellipsoids are shown at the the 50% probability level. 50% probability level. Molecules 2021, 26, 4985 3 of 10 Molecules 2021, 26, x FOR PEER REVIEW 3 of 10 FigureFigure 2. SingleSingle molecules molecules of of1 (1a),( a2), (b2), (andb), and3 (c),3 arranged(c), arranged to show to position show position of S-I-I relative of S-I-I to relative dithiane to ring dithiane plane. ring Hydrogen plane. Hydrogenatoms have atoms been haveomitted been for omitted clarity.for Atomic clarity. displacement Atomic displacement ellipsoids ellipsoidsare shown are at the shown 50% at probability the 50% probability level. level. Table 1.TableS···I-I 1. interactionS···I-I interaction distances distances (Å) and (Å) angles and angles (◦). (°). a Crystal dS-I dI-I θS-I-I θring-Ia-I Crystal dS-I dI-I qS-I-I qring-I-I 1 2.7124(4) 2.85193(18) 179.438(9) 52.29(3) 1 2.7124(4) 2.85193(18) 179.438(9) 52.29(3) 2 2 2.7465(6)2.7465(6) 2.8364(2) 2.8364(2) 176.579(12)176.579(12) 85.45(4)85.45(4) 2.8135(9)2.8135(9) 2.8072(4) 2.8072(4) 177.140(18)177.140(18) 40.70(6)40.70(6) 3 3 2.8329(9)2.8329(9) 2.7874(4) 2.7874(4) 176.229(18)176.229(18) 49.07(7)49.07(7) 4 4 3.0813(7)3.0813(7) 2.7827(4) 2.7827(4) 179.074(12)179.074(12) 38.25(5)38.25(5) 5 2.7891(6) 2.8117(3) 178.576(11) 42.78(5) 5 2.7891(6) 2.8117(3) 178.576(11) 42.78(5) 6 2.8036(7) 2.8031(3) 177.426(16) 47.40(5) a: angle calculated6 between2.8036(7) I-I bond and RMS plane2.8031(3) of dithiane ring.