Structures of the 2:1 adducts of benzyne with2-methylanisole and benzene

Christopher O. Bender, René T. Boeré, Peter W. Dibble, and Ryan T. McKay

Abstract: The 2:1 adduct of benzyne with 2-methylanisole is shown to have the bisbenzotricyclic structure6,6a,11,11a-tetrahydro-5-methoxy-6-methyl-5,6,11-metheno-5H-benzo[a]fluorene by a single-crystal X-ray diffractionstudy (C20H18O: Pca21, a = 15.0497(17), b = 9.87783(11), c = 9.6846(11); Z = 4; 1672 data points, R1 = 0.0325). Thisstructure is compared to an unpublished crystal structure of the parent hydrocarbon 6,6a,11,11a-tetrahydro-5,6,11-metheno-5H-benzo[a]fluorene, C18H14. Both structures have also been computed by DFT methods at the B3LYP/6–311(d,p) level of theory. Bond distances and angles between the solid-state measurements and gas-phase calculationsare found to agree well; average deviations are well below 1%. The 1H NMR spectra show surprisingly small 3JHH

couplings in the central tricyclic cage, but can be assigned using 2D spectroscopy.

Key words: Hydrocarbon cages, strained rings, cyclopropane, X-ray crystallography, NMR.

Résumé : Faisant appel à la diffraction des rayons X par un cristal unique, on a montré que l’adduit 2:1 de benzynesur le 2-méthylanisole possède la structure 6,6a,11,11a-tétrahydro-5-méthoxy-6-méthyl-5,6,11-méthéno-5H-benzo[a]fluo-rène [C2oH18O: Pca21, a = 15,04997(17), b = 9,8778(11) et c = 9,6846(11); Z = 4; 1672 données; R1 = 0,325). Oncompare cette structure à une structure cristalline non publiée de l’hydrocarbure fondamental 6,6a,11,11a-tétrahydro-5,6,11-méthéno-5H-benzo[a]fluorène, C18H14. On a aussi calculé les deux structures par des méthodes de la théorie dela fonctionnelle de densité au niveau B3LYP/6-311(d,p) de la théorie. On a trouvé que les distances et les angles deliaison des mesures de l’état solide et des calculs en phase gazeuse concordent bien; les déviations moyennes sont bienen dessous de 1%. Les spectres RMN du 1H présentent des couplages 3JHH qui sont très faibles dans la cage tricy-clique centrale, mais qui peuvent être attribués en faisant appel à la spectroscopie 2D.

Mots-clés : cages d’hydrocarbures, cycles tendus, cyclopropane, diffraction des rayons X, RMN.

[Traduit par la Rédaction] Bender et al. 465

Introduction

Compound 1 is obtained as a major side-product in thepreparation of 2-methyl-1-methoxy-4-hydro-1,4-etheno-naphthalene from the reaction of benzyne in neat 2-methylanisole (1). The structure of 1 is not readily deducedfrom the spectroscopic data; therefore, a single-crystal X-raydiffraction study was initiated. In this paper, we report thestructure of 1, 6,6a,11,11a-tetrahydro-5-methoxy-6-methyl-5,6,11-metheno-5H-benzo[a]fluorene and compare it to thatreported for the parent hydrocarbon 2, 6,6a,11,11a-tetrahydro-5,6,11-metheno-5H-benzo[a]fluorene. Since theinitial reports of the synthesis of 2 (2, 3), it has been of in-

terest for the preparation of benzannelated annulenes (4–6).Although the structure of 2 has also been determined by X-ray crystallography (7),4 the details are neither in the openliterature nor in the Cambridge Crystallographic Database.Therefore, we report here the derived geometric parametersof 1 and 2, as well as a comparison between those commonto both structures. In view of the unique structure of the cen-tral tricyclic cage common to both 1 and 2, which also con-tains a highly strained 3-membered ring, we have computedthe structure using hybrid DFT methods at the B3LYP/6–311(d,p) level of theory. There is excellent agreement be-tween the calculated gas-phase and the measured solid-stategeometries.

Experimental

Compound 1 was prepared as reported in ref. 1. Its high-resolution mass spectrum (EI, 70 eV) is consistent with theproposed formula, displaying only five high-intensity peaks

Can. J. Chem. 85: 461–465 (2007) doi:10.1139/V07-058 © 2007 NRC Canada

461

Received 14 February 2007. Accepted 30 May 2007.Published on the NRC Research Press Web site atcanjchem.nrc.ca on 22 June 2007.

C.O. Bender,1 R.T. Boeré,2 P.W. Dibble, andR.T. McKay.3 Department of Chemistry and Biochemistry,University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.

1In retirement.2Corresponding author (e-mail: boere@uleth.ca).3Present address: NANUC Building, Room 105, University ofAlberta, Edmonton, AB T6G 2E1, Canada.

4C18H14: Orthorhombic, P212121 (No. 19), a = 9.947(5), b =15.064(2), c = 8.073(2); collected with Cu Kα radiationusing the oscillation method.

as follows: 274.1356 (calcd. for C20H18O+ 274.1358, 81%);

259 (C19H15O+, 100%); 244 (C18H12O

+, 64%); 228 (C18H12+,

74%); and 215 (C17H11+, 70%). Significantly, there is no

peak resulting from a retro Diels–Alder process. NMR data(1H, 13C, 1H–1H COSY, HMBC, and HSQC experiments) of1 were collected on a Bruker AVANCE-II spectrometer op-erating at 300.13 MHz for 1H and 75.41 MHz for 13C andare reported w.r.t. the CHCl3 (1H: 7.29 ppm) and CDCl3(13C: 77.23 ppm) resonances. 1H: δ 1.07 (s, 3H), 1.29 (t, J =1.3 Hz, 1H), 2.44 (s, 1H), 2.75 (s, 1H), 2.93 (s, 1H), 3.55 (s,3), 7.04–7.26 (m, 7H), 7.5–9 (d, J = 8.0 Hz, 1H). Selectivedecoupling at 2.93 and 2.75 ppm collapsed the 1.29 ppmtriplet to a doublet, while decoupling the singlet at 2.44 ppmhad no effect. Irradiation of the singlet at 2.93 ppm sharp-ened the signal at 2.44 ppm. 13C: δ 10.92, 35.05, 38.41,44.52, 49.82, 56.95, 57.76, 74.97, 121.80, 121.88, 123.24,124.71, 124.83, 125.03, 125.29, 126.57, 135.28, 136.00,149.34, 149.54.

Details of the crystal and the structure determination of 1are summarized in Table 1. The space-group determinationwas problematic. Statistics favored Pbcm, but we were un-able to solve the structure in this space group. The secondchoice Pca21, No. 29, is a polar non-centrosymmetric spacegroup. The structure was solved by direct methods usingSHELXS (8), expanded using Fourier techniques, and re-fined with SHELXL (9). Non-hydrogen atoms were refinedanisotropically. Hydrogen atoms were included using a rid-ing model. Neutral atomic-scattering factors were takenfrom the International Tables (10). Selected bond distancesand angles are presented in Table 2, and an exhaustive list-ing is provided in the Supplementary Materials.5 A thermalellipsoids plot showing the structure of 1 and the atom-numbering sequence used for both 1 and 2 throughout thediscussion is presented in Fig. 1. Since all H atoms areplaced by geometry, their positions are only approximate.The approximate shortest contacts in the structure are be-tween C3 and H7 (2.73 Å), C4A and H6A (2.88 Å), C3 andH10 (2.88 Å), and C9 and H3 (2.86 Å), all just slightlyshorter than the sums of the van der Waals radii of C and H(2.90 Å).

The starting point for the DFT calculations was the crystalgeometry of 1, imported via Mercury 1.4.1 (11) intoGaussView (12). Calculations were performed in theGaussian 98W suite of programs (13), and the convergedminimum structures were confirmed by frequency calcula-tions, which report no imaginary frequencies.

Results and Discussion

The structure of 1 is depicted in Fig. 1 (one enantiomer).The central tricylic structure consists of two cyclohexanerings in twist-boat conformations that share four adjacent at-oms along one “side” of the boat. One end of each boat par-ticipates in a fused cyclopentane ring, which itself is in an

envelope conformation; the other end is bridged on the non-fused side by a single bond, thereby creating a cyclopropanering. Angles within the six-membered rings deviate consid-erably from the ideal tetrahedral angle (avg. deviation = 7 ±2°) mostly to expanded values, while in the five-memberedring, the angles are highly compressed (avg. deviation = 8 ±5°). The cyclopropane ring is close to ideal (avg. angles =60.0 ± 0.7°).

The crystal structure of 2 was determined many years agoby photographic methods (7), but it is only available in a

© 2007 NRC Canada

462 Can. J. Chem. Vol. 85, 2007

Crystal C20H18O

Formula weight 274.34Crystal system OrthorhombicSpace group Pca21 (No. 29)

a (Å) 15.0497(17)b (Å) 9.7783(11)c (Å) 9.6846(11)V (Å3) 1425.2(3)Z 4Dm Not measured

Dx (Mg/m3) 1.279

Appearance Colourless needlesCrystal size (mm3) 0.48 × 0.26 × 0.14Temperature (K) 173(2) KWavelength (λ) (Å) 0.71073Absorption coefficient (µ) (mm–1) 0.077Radiation Mo KαCrystallization solvent HexanesInstrument for data collection Bruker APEX IIθ range for data collection (°) 2.08–27.11Completeness to θ = 27.11° 100%Scans ωh –19 → 19k –12 → 12l –12 → 12Measured reflections 15181Independent reflections 1672 (Rint = 0.0213)

Reflections with I > 2 σ(I) 1672Absorption correction NoneIntensity decay NoneRefinement method Refinement on F2

H atoms ConstrainedGOF on F2 1.054restraints/parameters 1/193R [F2 > 2σ(F2)] 0.0325R [F2, all data] 0.0341wR(F2) 0.0935(D/σ)max 0.000

Dρmax (e Å–3) 0.232

Dρmin (e Å–3) –0.181

Table 1. Crystal data and structure refinement for 1.

5 Supplementary data for this article (crystallographic disorder modeling attempts, details of 1H NMR assignments, and full bond-lengths andbond-angles data) are available on the journal Web site (canjchem.nrc.ca) or may be purchased from the Depository of Unpublished Data,Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0S2, Canada. DUD 5179. For more information on ob-taining material refer to http://cisti-icist.nrc-cnrc.gc.ca/irm/unpub_e.shtml. CCDC 635872 contains the crystallographic data for this manu-script. These data can be obtained, free of charge, via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge CrystallographicData Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1233 336033; or deposit@ccdc.cam.ca.uk).

Ph.D. thesis (14). In Table 2, we compare bond lengths andangles for this structure with those that we obtained for 1.As expected, the more-recent structure determination ismore precise: the average value of the standard deviations inbond distances is 0.18% in 1 and 0.31% in 2, while for bondangles, these values are 0.14% and 0.32%, respectively (15).While significant, the small absolute differences speak togood precision for the older structure. The largest deviationbetween the two X-ray structures is in the C6—C12cyclopropane-ring bond, which in 2 is 0.09 Å shorter than in1 (1.9% deviation). Only three other bond distances deviateby more than 1%: C6B—C7, C4A—C5, and C4A—C11B.Similarly, only six internal bond angles differ between thetwo X-ray structures by more than one percent, and these areall angles associated with atoms of the central cage (C5, C6,C6A, C11A, and C12).

The structures of 1 and 2 are due to Diels–Alder additionof benzyne to a benzene derivative (Scheme 1). The firststep is a 1,4-cycloaddition to give a benzobarrelene 5; it iswell-known that tetrahalobenzynes react with toluene to giveadducts in which the non-bridgehead product predominates;whereas in the addition to anisole, the bridgehead adductspredominate (16, 17). The proposed intermediate 5 (X =OCH3, Y = CH3) is therefore the expected product from theaddition of benzyne, 3, to 2-methylanisole, 4 (X = OCH3,Y = CH3). Subsequent 1,3-cycloaddition by a second mole-cule of benzyne to the 3,5 carbon atoms gives the observedproducts (Scheme 1).

The closest-related structure to 1 and 2 in the CambridgeDatabase is that of dimethyl-1-cyano-1,1a,2,8,8a,8b-hexahydro-2,3,8-methanetriylcyclopropa[a]fluorene-3,3a-dicarboxylate (6) (18, 19). This molecule shares the same

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Bender et al. 463

1 (Crystal)a 1 (DFT)a 2 (Crystal)b 2 (DFT)a

Bond lengths (Å)C4A—C11B 1.398(2) 1.4006 1.385(4) 1.4016C4A—C5 1.480(2) 1.4807 1.464(5) 1.4742C5—C6 1.523(3) 1.5395 1.517(5) 1.5304C5—C12 1.529(2) 1.5351 1.516(4) 1.5304C6A—C6B 1.519(2) 1.5196 1.520(4) 1.5205C6A—C6 1.544(3) 1.5524 1.532(4) 1.5413C6A—C11A 1.560(2) 1.5711 1.564(4) 1.5737C6B—C10A 1.403(2) 1.4088 1.394(4) 1.4089C10A—C11 1.521(3) 1.5194 1.517(4) 1.5205C11—C12 1.536(2) 1.5397 1.522(4) 1.5413C11—C11A 1.564(3) 1.5725 1.558(4) 1.5737C11A—C11B 1.487(2) 1.4901 1.498(4) 1.4918C6—C12 1.508(3) 1.5131 1.480(5) 1.5052

Bond angles (°)C11B–C4A–C5 114.56(15) 115.18 115.5(4) 115.19C4A–C5–C6 118.76(15) 118.84 119.4(4) 119.38C4A–C5–C12 119.74(15) 119.65 119.3(4) 119.38C6–C5–C12 59.23(12) 58.97 58.4(2) 58.91C6B–C6A–C6 103.59(15) 105.11 105.3(3) 105.30C6B–C6A–C11A 99.13(15) 99.27 99.1(3) 99.38C6–C6A–C11A 102.19(15) 102.29 100.7(3) 101.30C10A–C6B–C6A 106.89(18) 106.67 106.6(3) 106.67C6B–C10A–C11 106.73(17) 106.62 106.8(3) 106.67C10A–C11–C12 103.93(15) 105.34 104.7(3) 105.3C10A–C11–C11A 99.23(14) 99.33 99.6(3) 99.38C12–C11–C11A 101.24(14) 101.01 101.2(3) 101.30C11B–C11A–C6A 112.95(15) 115.18 114.7(3) 114.44C11B–C11A–C11 114.39(15) 113.60 113.8(3) 114.44C6A–C11A–C11 93.89(13) 92.95 93.1(2) 92.90C4A–C11B–C11A 115.93(15) 115.44 115.0(3) 115.22C12–C6–C5 60.60(13) 60.37 60.8(3) 60.54C12–C6–C6A 103.91(16) 103.13 104.9(3) 104.58C5–C6–C6A 116.39(16) 116.19 118.2(4) 117.65C6–C12–C5 60.17(13) 60.66 60.8(2) 60.54C6–C12–C11 105.21(16) 105.57 105.0(3) 104.58C5–C12–C11 118.13(16) 118.27 118.1(3) 117.65

aThis work.bFrom ref. 14.

Table 2. Selected inter-atomic distances (Å) and (°) for 1 and 2 from crystallography and DFTcalculations.

central-cage structure, the “horizontal” fused benzo group,and a single substituent on the C6 atom of the cyclopropanering.

There is notable agreement among the three X-ray struc-tures (1, 2, and 6) that contain the same strained central car-bon cage. The greatest variance is found within the fusedcyclopropane rings. To further characterize this unusualstrained cage structure, we have performed full structureoptimizations using modern DFT methods. The geometricalresults of these calculations are also included in Table 2. Thenormalized average deviations between calculated bond dis-tances from the gas-phase theoretical and the solid-state ex-perimental structure determinations is 0.41% for 1 and0.72% for 2. For the bond angles, these values are 0.44%and 0.35%, respectively. The computed structure of 2 adopts

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464 Can. J. Chem. Vol. 85, 2007

Fig. 1. Thermal ellipsoid plot (50% probability, except H) produced in XSHELL 6.3.1 (Bruker, 2005) showing the structure of one en-antiomer of 1 and the atom-numbering sequence used for both 1 and 2. The H-atom radii are arbitrary.

Scheme 1. Proposed mechanism for the synthesis of 1 and 2.

Cs symmetry naturally; the computed structure of 1 has a re-markably similar orientation of the flexible O1–C14methoxy substituent groups to that found in the solid-statestructure, though the angles associated with this group hadthe largest normalized deviation in the case of 1. In contrastto the good agreement to the DFT calculations, the geometryreported for 2 obtained from a Consistent Valence ForceField contains deviations as high as 6% among the seven in-ternal bond distances listed for comparison (normalized avg.deviation = 2.7%) (4).

The NMR spectra of 2 are consistent with the structuredetermined from the X-ray diffraction study. Taken as awhole, the 1D and 2D NMR experiments support the assign-ments in Table 3.

Acknowledgements

We thank the Natural Sciences and Engineering ResearchCouncil of Canada (NSERC) and the University ofLethbridge for funding. Dr. M. Parvez (University of Cal-gary) collected an earlier data set on 1.

References

1. C.O. Bender, D.L. Bengtson, D. Dolman, and R.T. McKay.Can. J. Chem. 72, 1556 (1994).

2. L. Friedman. J. Am. Chem. Soc. 89, 3071 (1967).3. M. Stiles, U. Burckhardt, and G. Freund. J. Org. Chem. 32,

3718 (1967).4. M. Banciu, D. Elian, M. Elian, L. Stanescu, and A.

Cioranescu. Rev. Roum. Chim. 31, 503 (1986).5. M.D. Banciu, C. Hada, D. Albaiu, and C. Drachigi. Rev.

Roum. Chim. 34, 1907 (1989).6. C. Hada, J.-C. Roussel, P. Beccat, R. Boulet, and M.D. Banciu.

Rev. Roum. Chim. 42, 777 (1997).7. J.W. Schilling and C.E. Norman. Abstracts of the American

Crystallographic Association Meeting. Atlanta, Ga. 1967. p22.

8. G. Sheldrick. SHELXS-97 [computer program]. University ofGöttingen, Göttingen, Germany. 1997.

9. G. Sheldrick. SHELXL-97 [computer program]. University ofGöttingen, Göttingen, Germany. 1997.

10. D.C. Creagh and W.J. McAuley. International Tables for X-rayCrystallography, Vol. C. Table 4.2.6.8. Kluwer Academic Pub-lishers, Boston. 1992. p. 219.

11. Mercury 1.4.1 [computer program]. Cambridge Crystallo-graphic Data Centre (2001–2005).

12. Semichem. GaussView 2.1 [computer program]. Gaussian,Inc., Pittsburg, PA, USA. 2001.

13. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A.Robb, J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery,Jr., R.E. Stratmann, J.C. Burant, S. Dapprich, J.M. Millam,A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi,V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C.Adamo, S. Clifford, J. Ochterski, G.A. Petersson, P.Y. Ayala,Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck, K.Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, B. B.Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham,C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe,P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, J. L. Andres,C. Gonzalez, M. Head-Gordon, E.S. Replogle, and J.A. Pople.Gaussian 98 [computer program]. Revision a.6. Gaussian, Inc.,Pittsburg, PA, USA. 1998.

14. J.W. Schilling. Ph.D. Thesis, University of Michigan. 1968.15. G.H. Stout and L.H. Jensen. X-ray structure determination: a

practical guide. 2nd ed. Wiley, NY. (1989). p. 404.16. P.C. Buxton, N.J. Hales, B. Hankinson, H. Heaney, S.V. Ley,

and R.P. Sharma. J. Chem. Soc., Perkin I. 1974 (1974).17. Hankinson and H. Heaney. Tetrahedron. Lett. 1355 (1970).18. K. Saito, M. Kozaki, A. Imai, Y. Hara, and K. Takahashi.

Chem. Lett. 1769 (1994).19. K. Saito, K. Ono, T. Takeda, S. Kiso, K. Uenishi, and M.

Kozaki. Tetrahedron. 58, 9081 (2002).

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Bender et al. 465

1 2a

Position δ(1H) δ(13C) δ(1H) δ(13C)

5 — 74.97 2.95 31.76 — 38.41 1.70 25.86A 2.44 49.82 2.70b 43.0c

11 2.75 44.52 2.70b 43.0c

11a 2.93 57.76 3.32 56.4d

12 1.29 35.05 1.70 25.8Me 1.07 10.92 — —OMe 3.55 56.95 — —4 7.59 121.80 — —4A — 135.48 — —6B — 149.34 — —10A — 149.54 — —11B — 136.00 — —

Note: Atom-numbering scheme is the same as that used in the crystalstructure. Hydrogen atoms are attached to carbons of the same number.

aTaken from ref. 6 (1H in CD2Cl2,13C in CDCl3); quart: 151.0, 151.0,

136.5, 135.5; tert: 126.8, 125.8, 125.6, 124.9, 124.5, 122.0.bCompare with 2.8 ppm for the bridgehead position in norbornene.cCompare with 42 ppm in norbornene.dCompare with 49 ppm in norbornene.

Table 3. NMR peak assignments for 1 and 2.