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Short Note Tetrahydro-1,4--3,5-dioneShort Note Tetrahydro-1,4-thiazine-3,5-dione R. Alan Aitken * , Alexandra M. Z. Slawin and Pei-pei Yeh R.EaStCHEM Alan Aitken School *, Alexandra of Chemistry, M. University Z. Slawin of Stand Andrews, Pei-pei North Yeh Haugh, St Andrews Fife KY16 9ST, UK; [email protected] (A.M.Z.S.); [email protected] (P.-p.Y.) EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews Fife KY16 9ST, UK; * Correspondence: [email protected]; Tel.: +44-1334-463865 [email protected] (A.M.Z.S.); [email protected] (P.-p.Y.) * Correspondence: [email protected]; Tel.: +44-1334-463865  Received: 30 November 2018; Accepted: 12 December 2018; Published: 13 December 2018  Received: 30 November 2018; Accepted: 12 December 2018; Published: date Abstract: The X-ray structure of the title compound contains eight molecules in the unit cell which formAbstract: the basisThe X-ray of a herringbone structure of arrangement the title compound of hydrogen contains bonded eight ribbons. molecules in the unit cell which form the basis of a herringbone arrangement of hydrogen bonded ribbons. Keywords: tetrahydro-1,4-thiazine-3,5-dione; X-ray structure; hydrogen bonding Keywords: tetrahydro-1,4-thiazine-3,5-dione; X-ray structure; hydrogen bonding

1. Introduction The simplesimple heterocyclic compound tetrahydro-1,4-thiazine-3,5-dione tetrahydro-1,4-thiazine-3,5-dione (or -3,5-dione) (or thiomorpholine-3,5- 1dione), the cyclic 1, the imide cyclic of imide thiodiglycolic of thiodiglycolic acid 2, was acid first 2 prepared, was first in prepared 1948 [1], andin 1948 IR and [1], NMR and spectroscopicIR and NMR dataspectroscopic were reported data were in 2001 reported [2]. in Following 2001 [2]. ourFollowing recent our report recent of report the first of generationthe first generation of the parent of the 1,4-oxazineparent 1,4-oxazine [3], we [3], were we interestedwere interested to explore to expl routesore routes to the to analogousthe analogous 1,4-thiazine 1,4-thiazine and and many many of theseof these attempts attempts have have involved involved starting starting from from1, although1, although we we have have so farso beenfar been unable unable to reproduce to reproduce the reportedthe reported [1] direct [1] direct reduction reduction of 1 to of 1,4-thiazine 1 to 1,4-thiazine over over aluminium powder. powder. In the courseIn the ofcourse these of studies, these compoundstudies, compound1 has been 1 preparedhas been in prepared large quantity in large and quantity we report and here we the report molecular here and thecrystal molecular structure and ofcrystal1 as determinedstructure of 1 by as X-ray determined diffraction. by X-ray The diffraction. observed crystal The observed structure crystal is discussed structure in comparisonis discussed within comparison those in similar with those previously in similar reported previously structures. reported structures.

2. Results Compound 11was was readily readily prepared prepared using theusing literature the literature method [ 1]method involving [1] heating involving commercially heating availablecommercially thiodiglycolic available thiodiglycolic acid 2 with an acid excess 2 with of aqueous an excess ammonia of aqueous and ammonia distilling and off the distilling water, firstoff the at atmosphericwater, first at pressure atmospheric and finallypressure under and vacuumfinally under (Scheme vacuum1). The (Scheme residue 1). was The subjected residue was to kugelrohr subjected distillationto kugelrohr to distillation give the product to give as the colourless product crystals as colourless which crystals were directly which suitable were directly for the suitable X-ray structure for the determination.X-ray structure Bothdetermination. IR and NMR Both (CD 3IRSOCD and 3NMR) spectra (CD were3SOCD in agreement3) spectra withwere previouslyin agreement reported with 1 13 valuespreviously [2], butreported we have values also recorded[2], but weH- have and alsoC-NMR recorded data in1H- CDCl and3 (see13C-NMR Experimental data in SectionCDCl3 and(see SupplementaryExperimental Section Material). and Supplementary Material).

O 1. aq. NH3 S S S 2. heat, − H O 2 = HN

CO2H CO2H O N O O H 2 1 Scheme 1. Synthetic route to 1 [[1].1].

In the X-ray structure there are two distinct moleculesmolecules (Figure 11,, TablesTables1 1and and2) 2) both both of of which which show anan “envelope”“envelope” structure structure with with the the sulfur atom atom above above the the plane plan containinge containing the imidethe imide function function and two CH groups. The molecular dimensions are similar but slightly different which reflects the different and two2 CH2 groups. The molecular dimensions are similar but slightly different which reflects the roledifferent of the role two of molecules the two inmolecules the hydrogen-bonding in the hydrog patternen-bonding (each pattern molecule (each is hydrogen-bonded molecule is hydrogen- to two ofbonded the opposite to two type).of the Inopposite the first type). molecule In the the first sulfur molecule atom isthe 0.865 sulfur Å aboveatom is the 0.865 mean Å planeabove formed the mean by plane formed by C(2), C(3), N(4), C(5) and C(6) and the plane containing C(2), S(1) and C(6) is at an Molbank 2018, 2018, M1036; doi:10.3390/M1036 www.mdpi.com/journal/molbank Molbank 2017, 2017, M9xx; doi: FOR PEER REVIEW www.mdpi.com/journal/molbank Molbank 2018, 2018, M1036 2 of 5

Molbank 2017, 2017, M9xx FOR PEER REVIEW 2 of 5 C(2), C(3), N(4), C(5) and C(6) and the plane containing C(2), S(1) and C(6) is at an angle of 46.27◦ to ° theangle first of plane. 46.27 Forto the the first second plane. molecule For the the second corresponding molecule the parameters corresponding are 0.897 parameters Å and 48.15 are◦ .0.897 In the Å ° unitand cell48.15 there. In are the eight unit molecules,cell there are four eight of each molecules, type, and four these of areeach arranged type, and ina these “herringbone” are arranged pattern in a when“herringbone” viewed along pattern the when a axis viewed (Figure 2along). the a axis (Figure 2).

Figure 1. The two distinct molecules in the molecular structure of 1 with numbering scheme. Figure 1. The two distinct molecules in the molecular structure of 1 with numbering scheme. Table 1. Selected bond lengths.

Bond Length/ÅTable 1. Selected bond lengths. Bond Length/Å S(1)–C(2)Bond 1.804(2)Length/Å Bond S(11)–C(12) Length/Å 1.799(2) S(1)–C(6)S(1)–C(2) 1.807(3)1.804(2) S(11)–C(12) S(11)–C(16) 1.799(2) 1.797(3) O(3)–C(3) 1.230(3) O(13)–C(13) 1.231(3) S(1)–C(6) 1.807(3) S(11)–C(16) 1.797(3) O(5)–C(5) 1.227(3) O(15–C(15) 1.223(3) N(4)–C(3)O(3)–C(3) 1.375(3)1.230(3) O(13)–C(13) N(14)–C(13) 1.231(3) 1.370(3) N(4)–C(5)O(5)–C(5) 1.400(3)1.227(3) O(15–C(15) N(14)–C(15) 1.223(3) 1.396(3) N(4)–H(4N)N(4)–C(3) 0.975(5)1.375(3) N(14)–C(13) N(14)–H(14N) 1.370(3) 0.976(5) C(2)–C(3)N(4)–C(5) 1.500(3)1.400(3) N(14)–C(15) C(12)–C(13) 1.396(3) 1.503(3) C(5)–C(6) 1.496(3) C(15)–C(16) 1.503(3) N(4)–H(4N) 0.975(5) N(14)–H(14N) 0.976(5) C(2)–C(3) 1.500(3) C(12)–C(13) 1.503(3) Table 2. Selected angles. C(5)–C(6) 1.496(3) C(15)–C(16) 1.503(3) Angle Value/◦ Angle Value/◦ C(2)–S(1)–C(6) 97.48(11)Table 2. Selected C(12)–S(11)–C(16) angles. 96.37(11) C(3)–N(4)–C(5)Angle 129.08(19)Value/° C(13)–N(14)–C(15)Angle Value/° 128.60(19) C(3)–N(4)–H(4N) 113.0(13) C(13)–N(14)–H(14N) 114.6(15) C(5)–N(4)–H(4N)C(2)–S(1)–C(6) 117.4(13)97.48(11) C(12)–S(11)–C(16) C(15)–N(14)–H(14N) 96.37(11) 116.6(15) C(3)–C(2)–S(1)C(3)–N(4)–C(5) 112.69(16)129.08(19) C(13)–N(14)–C(15) C(13)–C(12)–S(11) 128.60(19) 113.30(16) O(3)–C(3)–N(4)C(3)–N(4)–H(4N) 118.8(2)113.0(13) C(13)–N(14)–H(14N) O(13)–C(13)–N(14) 114.6(15) 119.0(2) O(3)–C(3)–C(2)C(5)–N(4)–H(4N) 122.1(2)117.4(13) C(15)–N(14)–H(14N) O(13)–C(13)–C(12) 116.6(15) 122.1(2) N(4)–C(3)–C(2) 119.03(19) N(14)–C(13)–C(12) 118.85(19) O(5)–C(5)–N(4)C(3)–C(2)–S(1) 119.2(2)112.69(16) C(13)–C(12)–S(11) O(15)–C(15)–N(14) 113.30(16) 118.6(2) O(5)–C(5)–C(6)O(3)–C(3)–N(4) 121.6(2)118.8(2) O(13)–C(13)–N(14) O(15)–C(15)–C(16) 119.0(2) 121.8(2) N(4)–C(5)–C(6)O(3)–C(3)–C(2) 119.2(2)122.1(2) O(13)–C(13)–C(12) N(14)–C(15)–C(16) 122.1(2) 119.5(2) C(5)–C(6)–S(1)N(4)–C(3)–C(2) 115.51(16)119.03(19) N(14)–C(13)–C(12) C(15)–C(16)–S(11) 118.85(19) 114.20(17) O(5)–C(5)–N(4) 119.2(2) O(15)–C(15)–N(14) 118.6(2) O(5)–C(5)–C(6) 121.6(2) O(15)–C(15)–C(16) 121.8(2) N(4)–C(5)–C(6) 119.2(2) N(14)–C(15)–C(16) 119.5(2) C(5)–C(6)–S(1) 115.51(16) C(15)–C(16)–S(11) 114.20(17) Molbank 2017, 2017, M9xx FOR PEER REVIEW 3 of 5 Molbank 2018, 2018, M1036 3 of 5 Molbank 2017, 2017, M9xx FOR PEER REVIEW 3 of 5

Figure 2. Unit cell of 1 viewed along the a axis showing the 8 molecules present along with their Figurehydrogen 2. UnitUnitbonded cell cell partners. of of 1 viewed along the a axis showing the 8 molecules present along with their hydrogen bonded partners. The key feature of the overall structure is that each of the eight molecules in the unit cell forms The key feature of the overall structure is that each of the eight molecules in the unit cell the basisThe keyof afeature hydrogen-bonded of the overall ribbon structure (Figure is that 3) eainch which of the each eight molecule molecules has in itsthe NHunit hydrogen-cell forms forms the basis of a hydrogen-bonded ribbon (Figure3) in which each molecule has its NH thebonded basis to of CO a hydrogen-bondedof an adjacent molecule ribbon and (Figure only one3) in of which its CO each groups molecule hydrogen-bonded has its NH tohydrogen- NH of a hydrogen-bonded to CO of an adjacent molecule and only one of its CO groups hydrogen-bonded to bondedneighbour to COon the of another adjacent side. The molecule parameters and only (Table one 3) ofshow its CO two groups strong hydrogen-bondedand closely similar tohydrogen- NH of a NH of a neighbour on the other side. The parameters (Table3) show two strong and closely similar neighbourbonding interactions. on the other side. The parameters (Table 3) show two strong and closely similar hydrogen- hydrogen-bonding interactions. bonding interactions. Table 3. Hydrogen bonding parameters for 1 (Å, °). Table 3. Hydrogen bonding parameters for 1 (Å, ◦). ° Table… 3. Hydrogen bonding parameters… for… 1 (Å, ). … D—H A D—H H A D A D—H A D—H··· A … D—H H··· AD… …··· A… D—H··· A D—H …A D—H0.975(16) H1.938(16)A D2.894(3)A D—H166.1(15)A N(4)–H(4N)N(4)–H(4N)··· O(13) 0.975(16)O(13) 1.938(16) 2.894(3) 166.1(15) …… 0.975(16) 1.938(16) 2.894(3) 166.1(15) N(14)–H(14N)N(4)–H(4N)N(14)–H(14N)··· O(3) O(13)0.98(2)O(3) 0.98(2) 1.96(2)1.96(2) 2.917(3) 2.917(3) 167.3(18) 167.3(18) … N(14)–H(14N) O(3) 0.98(2) 1.96(2) 2.917(3) 167.3(18)

Figure 3. Hydrogen bonded ribbon in the structure of 1. Figure 3. Hydrogen bonded ribbon in the structure of 1. The onlyonly previous previous examples examples of thisof this heterocyclic heterocyclic ring systemring system to have to their have X-ray their structures X-ray structures reported arereported aThe series onlyare of Na previous-arylseries compounds of examplesN-aryl 3compounds– 9of(Figure this heterocyclic4) in3–9 which (Figure therering 4) is systemin no which opportunity to therehave their foris no hydrogen-bonding X-rayopportunity structures for reportedandhydrogen-bonding which are adopt a series a rangeand of which ofN-aryl different adopt compounds structures a range 3 of driven–9 diffe(Figure byrent molecular 4)structures in which stacking driven there interactions byis nomolecular opportunity [4]. stacking Perhaps for hydrogen-bondingtheinteractions closest literature [4]. Perhaps and comparison which the closest adopt is literature witha range the lactamcoof mparisondifferent thiomorpholine-3-one structuresis with the driven lactam 10 bythiomorpholine-3-one, molecular in which astacking similar interactionshydrogen-bonding10, in which [4].a similar Perhaps interaction hydrogen-bonding the closest leads literature to simple interaction co helicalmparison leads chains isto withofsimple molecules the helical lactam [5 chains]. thiomorpholine-3-one In the of corresponding molecules [5]. 10tetrahydro-1,4-oxazinedioneIn ,the in whichcorresponding a similar tetrahydro-1,4-oxazinedionehydrogen-bonding series also, thereinteraction have se been riesleads also, very to simplethere few previoushave helical been chains X-ray very of studiesfew molecules previous with [5]. the X- In the corresponding tetrahydro-1,4-oxazinedione series also, there have been very few previous X- Molbank 2018, 2018, M1036 4 of 5 Molbank 2017, 2017, M9xx FOR PEER REVIEW 4 of 5 rayN-aryl studies compound with the 11N-arylthe compound only example 11 the located only example [6], while located the parent [6], while dione the12 parentwith dione the different 12 with the2,5-arrangement different 2,5-arrangement of carbonyl groups of carbonyl has also groups been has reported also been [7]. reported [7].

S S S S S

O N O O N O O N O O N O N O H X tBu 10 (GIPLOG)

O O X O X 9 (POMGOP) 3 X = NO (POMFII) 6 (POMGEF) 2 7 X = F (POMFOO) O N O 4 X = OMe (POMGAB) 8 X = Cl (POMFUU) 5 X = Cl (POMGIJ) OMe O O

O N H NO2 12 (WEHYAK) 11 (XEYVON)

FigureFigure 4. 4. SimilarSimilar structures structures characterized characterized by by X-ray X-ray diffraction diffraction with with CCDC CCDC Ref Ref Codes. Codes.

InIn view ofof thethe interesting interesting hydrogen-bonding hydrogen-bonding pattern pattern discovered discovered for 1for, it 1 is, clearit is clear that there that isthere ample is ampleopportunity opportunity for further for further structural structural studies stud on suchies on simple such simple heterocyclic heterocyclic imides. imides. 3. Experimental 3. Experimental Melting points were recorded on a Reichert hot-stage microscope (Reichert, Vienna, Austria) and Melting points were recorded on a Reichert hot-stage microscope (Reichert, Vienna, Austria) are uncorrected. IR spectra were recorded on a Perkin-Elmer 1420 instrument (Perkin-Elmer, Waltham, and are uncorrected. IR spectra were recorded on a Perkin-Elmer 1420 instrument (Perkin-Elmer, MA, USA). NMR spectra were obtained for proton at 300 MHz and for at 75 MHz using a Waltham, MA, USA). NMR spectra were obtained for proton at 300 MHz and for carbon at 75 MHz Bruker AM300 instrument (Bruker, Billerica, MA, USA). Spectra were run at 25 ◦C on solutions in using a Bruker AM300 instrument (Bruker, Billerica, MA, USA). Spectra were run at 25 °C on CD3SOCD3 with internal Me4Si as reference. Chemical shifts are reported in ppm to high frequency of solutions in CD3SOCD3 with internal Me4Si as reference. Chemical shifts are reported in ppm to high the reference and coupling constants J are in Hz. frequency of the reference and coupling constants J are in Hz. Tetrahydro-1,4-thiazine-3,5-dioneTetrahydro-1,4-thiazine-3,5-dione (1) AqueousAqueous ammonia ammonia (d (d 0.88, 0.88, 18 18 M, M, 15 15 mL, mL, 270 270 mmol) mmol) was was added added cautiously cautiously to to thiodiglycolic thiodiglycolic acid acid (15(15 g, g, 100 100 mmol) mmol) in in a a flask flask set set up up for for distillation. distillation. The The mixture mixture was was slowly slowly heated heated and and water water distilled distilled offoff first first under under atmospheric atmospheric pressure pressure and and then then at at 20 20 Torr. Torr. The The residue residue was was then then subjected subjected to to Kugelrohr Kugelrohr ◦ distillationdistillation at at 0.1 0.1 Torr Torr to to give give the the pure pure product product (9.3 (9.3 g, g, 71%) 71%) as as colourless colourless crystals; crystals; mp mp 118–120 118–120 °CC (lit. (lit. ◦ −1 1 mpmp 128 128 °CC[ [1]);1]); IR (nujol): 3420, 1728, 1270, 1194, 1143,1143, 918,918, 856,856, 790,790, 657657 cmcm−1;; 1H-NMRH-NMR (300 (300 MHz, MHz, δ 13 δ 1 CDCD33SOCDSOCD3):3): δ 3.503.50 (s); (s); 13C-NMRC-NMR (75 (75 MHz, MHz, CD CD3SOCD3SOCD3):3 ):δ 170.5,170.5, 30.3; 30.3; 1H-NMRH-NMR (300 (300 MHz, MHz, CDCl CDCl3): 3δ): δ 13 δ 8.568.56 (1H, (1H, br, br, NH), NH), 3.48 3.48 (4H, (4H, s); s); 13C-NMRC-NMR (75 (75 MHz, MHz, CDCl CDCl3): 3δ): 168.8,168.8, 30.9. 30.9. −1 × CrystalCrystal Data for C44H5NONO22S,S, M M = = 131.15 131.15 g g mol −1, ,colourless colourless prism, prism, crystal crystal dimensions dimensions 0.12 × 0.120.12 × β ◦ × 0.120.12 mm, mm, monoclinic, monoclinic, space space group group P2 P21/n,1/n, a = a 7.173(3), = 7.173(3), b = b 18.603(6), = 18.603(6), c = c 8.393(4) = 8.393(4) Å, Å,β = 108.164(8)°,= 108.164(8) V , 3 −3 =V 1064.2(7) = 1064.2(7) Å3,Å Z ,=Z 8,= D 8,calc D =calc 1.637= 1.637 g cm g−3, cm T = 93, T K,= R1 93 = K, 0.0393, R1 = 0.0393, Rw2 = Rw20.0995 = 0.0995for 1661 for reflections 1661 reflections with I >with 2σ(I I) >and 2σ( 153I) and variables. 153 variables. Data were Data collected were collected using usinggraphite graphite monochromated monochromated Mo K Moα radiation Kα radiation λ = 0.71075λ = 0.71075 Å and Å have and been have deposited been deposited at the Cambridge at the Cambridge Crystallographic Crystallographic Data Centre Data as Centre CCDC as1867063. CCDC The1867063. data Thecan databe obtained can be obtained free of freecharge of chargefrom the from Cambridge the Cambridge Crystallographic Crystallographic Data DataCentre Centre via www.ccdc.cam.ac.uk/getstructures.via www.ccdc.cam.ac.uk/getstructures The. structure The structure was solved was solved by direct by direct methods methods and refined and refined by full- by 2 matrixfull-matrix least-squares least-squares against against F2 (SHELXL, F (SHELXL, Version Version 2018/3, 2018/3, [8]). Hydr [8]).ogen Hydrogen atoms were atoms assigned were assigned riding isotropicriding isotropic displacement displacement parameters parameters and constraine and constrainedd to idealised to idealised geometries geometries except except for H(4N) for H(4N) and H(14N)and H(14N) which which were were refined refined with witha distance a distance restraint. restraint.

Supplementary Materials: The following are available online, Figure S1: 300 MHz 1H-NMR spectrum of 1 in CDCl3, Figure S2: 75 MHz 13C-NMR spectrum of 1 in CDCl3. Molbank 2018, 2018, M1036 5 of 5

Supplementary Materials: The following are available online, Figure S1: 300 MHz 1H-NMR spectrum of 1 in 13 CDCl3, Figure S2: 75 MHz C-NMR spectrum of 1 in CDCl3. Author Contributions: P.-p.Y. prepared the compound; A.M.Z.S. collected the X-ray data and solved the structure; R.A.A. designed and performed the experiments, analysed the data and wrote the paper. Conflicts of Interest: The authors declare no conflict of interest.

References

1. Barkenbus, C.; Landis, P.S. The Preparation of 1,4-Thiazine. J. Am. Chem. Soc. 1948, 70, 684–685. [CrossRef] 2. Aitken, R.A.; Farrell, D.M.M.; Kirton, E.H.M. Synthesis and Pyrolysis of Tetrahydro-1,4-oxazine-3,5-diones and Tetrahydro-1,4-thiazine-3,5-diones. Chem. Heterocycl. Compd. 2001, 37, 1526–1531. [CrossRef] 3. Aitken, R.A.; Aitken, K.M.; Carruthers, P.G.; Jean, M.A.; Slawin, A.M.Z. 1,4-Oxazine. Chem. Commun. 2013, 49, 11367–11369. [CrossRef][PubMed] 4. Szawkalo, J.; Maurin, J.K.; Plucinski, F.; Czarnocki, Z. Synthesis and dynamic stereochemistry of 4-aryl-thiomorpholine-3,5-dione derivatives. J. Mol. Struct. 2015, 1079, 383–390. [CrossRef] 5. Ramasubbu, N.; Parthasarathy, R.; Tsoucaris, G. Structure of thiomorpholine-3-one: Comments on the geometry of monocoordinated metal complexes. Acta Crystallogr. Sect. C 1988, 44, 2016–2018. [CrossRef] 6. Bhuiyan, M.D.H.; Jensen, P.; Turner, P.; Try, A.C. 4-(2-Methoxy-4-nitrophenyl)-3,5-dione. Acta Crystallogr. Sect. E 2007, 63, o1115–o1116. [CrossRef] 7. Martínez-Palau, M.; Urpí, L.; Solans, X.; Puiggalí, J. Morpholine-2,5-dione. Acta Crystallogr. Sect. C 2006, 62, o262–o264. [CrossRef][PubMed] 8. Sheldrick, G.M. A short history of SHELXL. Acta Crystallogr. Sect. A 2008, 64, 112–122. [CrossRef][PubMed]

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