J Chem Crystallogr (2009) 39:453–457 DOI 10.1007/s10870-008-9502-z
ORIGINAL PAPER
Intermolecularly Associated Carboxylic Acid Dimers in the Supramolecular Assembly of (R)-1,4-Benzodioxane 2-Carboxylic Acid Jerry P. Jasinski Æ Ray J. Butcher Æ H. S. Yathirajan Æ B. Narayana Æ L. Mallesha Æ K. N. Mohana
Received: 5 August 2008 / Accepted: 13 November 2008 / Published online: 4 December 2008 Ó Springer Science+Business Media, LLC 2008
Abstract The title compound, C9H8O4, (I), crystallizes in the monoclinic space group P 21/c with unit ˚ , b = 9.3790(7) A ˚, c = cell parameters a = 7.3380(5) A ˚ , b = 90.687(7)°, Z = 4. The molecule con12.3172(9) A sists of a benzene ring fused to a 1,4 dioxane ring in a halfchair conformation with a carboxylic acid group bonded at the dioxane 2-position. The carboxylic acid group forms a classic O–HO hydrogen bonded dimer with an OO ˚ in a R22 (8) graph-set motif which distance of 2.6292(12) A links the molecules into pairs around inversion centers in a supramolecular assembly in the unit cell. The dihedral angle between the mean planes of the R22 (8) graph-set motif’s of two adjacent dimers in the unit cell is 75.7(5)°. The mean plane of an R22 (8) graph-set motif makes an angle of 88.4(5)° with the mean plane of the benzene ring in the same dimer and 13.1(2)° or 13.4(7)° with the mean
Electronic supplementary material The online version of this article (doi:10.1007/s10870-008-9502-z) contains supplementary material, which is available to authorized users. J. P. Jasinski (&) Department of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA e-mail:
[email protected] R. J. Butcher Department of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA H. S. Yathirajan L. Mallesha K. N. Mohana Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India B. Narayana Department of Studies in Chemistry, Mangalore University, Mangalagangotri, Mangalore 574 199, India
plane of a benzene ring from an adjacent dimer. Additional weak Cg p-ring intermolecular interactions significantly influence the bond distances, bond angles and torsion angles of the dioxane ring and attached carboxyl group. Comparison to a MOPAC AM1computational calculation provides support to these observations. Keywords Benzene Dioxane Carboxylic acid Dimer R22 (8) graph-set motif MOPAC
Introduction The chiral 2-substituted 1,4-benzodioxane system is a recurrent substructure [1, 2] in therapeutic agents while the absolute configuration of its stereogenic C2 often strongly influences the biological activity of molecules containing such a system. This is the main reason why a number of methods have been developed over the last 30 years for the preparation of enantiopure 1,4-benzodioxanes bearing, at the 2-position, substituents easily susceptible to further synthetic transformations, such as carboxyl, alkoxycarbonyl, vinyl or suitably functionalized methyl. These methods are based on resolution of the respective racemates, catalyzed by enzymes and non-biological asymmetric catalysts [3, 4] or accomplished after conversion into diastereomeric mixtures [5, 6], or on syntheses, which utilize asymmetric catalysts or start from chiral precursors belonging to the ‘chiral pool’, such as glycerol or glycidol derivatives [7–10]. The most recent examples, reported after 2000, are the palladium-catalyzed asymmetric cyclization of benzene-1,2-diol with allylic biscarbonates [11], the palladium-catalyzed intramolecular cyclization of non-racemic 1-(2-bromophenyl)glycerol [12] and the enzymatic resolutions of 1,4-benzodioxane-2-
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carboxylic acid [13], its ethyl ester [14] and 2-hydroxymethyl-1,4-benzodioxane [15]. In 2003, some efficient resolution methods were developed for 1,4-benzodioxane2-carboxylic acid with (?)-dehydroabietylamine, giving access to both enantiopure (R)- and (S)-acids. Over the course of studies on the resolution with (?)-dehydroabietylamine, it was demonstrated by DSC and IR analyses that 1,4-benzodioxane-2-carboxylic acid and 2 hydroxymethyl1,4-benzodioxane are racemic compounds, whereas the respective methyl ester and mesylate form conglomerates [16]. A chiral 2-substituted benzodioxane, namely (±)-1,4benzodioxane-2-carboxylic acid, (I), is readily available by condensation of catechol with ethyl 2,3-dibromopropionate and successive saponification of the intermediate ester [17]. The crystal structures of the salts of (S)- and (R)-1,4-benzodioxane-2-carboxylic acid with (S)-1-phenylethylamine and its p-methyl and p-nitro substituted analogues were determined in order to correlate the differences in solubility between diastereomeric salts with their solid state structures [18]. Structure-activity relationships in 1,4benzodioxan-related compounds have been established recently [19]. The present paper reports a crystal structure of the title compound, C9H8O4, {(R)-1,4-benzodioxane 2carboxylic acid}.
Experimental The title compound was obtained as gift sample from INTERMED LABS PRIVATE LTD., Bangalore, India. Crystals suitable for single-crystal X-ray diffraction were grown from acetonitrile by slow evaporation of solvent. The melting range was found to be 391–395 K.
J Chem Crystallogr (2009) 39:453–457 Table 1 Crystal and experimental data for (I) (I) CCDC deposit no.
697309
Formula
C9H8O4
Formula weight
180.15
Crystal color, habit
Colorless, chunk
Crystal size (mm)
0.48 9 0.44 9 0.35
Crystal system
Monoclinic
Space group, Z
P 21/c, 4
Temperature (K) ˚) a (A
7.3380(5)
200(2)
˚) b (A ˚ c (A)
9.3790(7)
b (o)
12.3172(9) 90.687(7)
˚3 Volume, A
847.65(11)
F(000)
376 -1
Absorption coef (mm )
0.113
Dcalc (Mg m-3)
1.412
No. of reflections [I [ 2r(I)]
2826
2hmax (o) with Mo Ka
65.0
R, Rw [I [ 2r(I)] ˚ -3) (Dq)max (e A
0.0427, 0.1213
˚ -3) (Dq)min (e A
-0.247
GOF on F2
1.143
Measurement
GEMINI (Oxford diffraction, 2007)
Program system
CrysAlisPro
Structure determination
SHELXS97
Refinement
Full-matrix least-squares on F2 (SHELXL97)
0.304
O O
Structure Determination and Refinement X-ray data for (I) was collected with an Oxford Diffraction Gemini R CCD area detector using CrysAlisPro software ˚ ) at and graphite-monochromated Mo-Ka (k = 0.71073 A 200(2) K. The structure was solved by direct methods using SHELXS97 [20] and all of the non-hydrogen atoms were refined anisotropically by full-matrix least-squares on F2 using SHELXL97 [20]. The hydrogen atoms were placed in their calculated positions and included in the refinement using the riding model. An absorption correction was performed using CrysAlis RED and all calculations were performed using SHELXTL [21]. Crystal and experimental data for (I) are listed in Table 1. A scheme for the molecular structure of (I) is shown in Fig. 1. Bond lengths and bond angles are all within expected ranges, Table 2 [22].
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HO
C
O
Fig. 1 Chemical structure of the title compound, C9H8O4, (I)
Results and Discussion The title compound consists of a benzene ring fused to a 1,4 dioxane ring in a half-chair conformation with a carboxylic acid group bonded at the dioxane 2-position. The puckering parameters [23] of the dioxane ring are Q, h and ˚ , 50.6(2)° and 69.715(4)°, respectively / of 0.477(6) A (Fig. 2). For a half-chair, h has a value of 50.8°. The carboxylic acid group forms a classic O–HO hydrogen ˚ bonded dimer with an O(1)O(2) distance of 2.6292(12) A 2 (Table 3) in a R2 (8) graph-set motif [24] which link the molecules into pairs around inversion centers in the unit cell (Fig. 2). This O(2)–H(2B)O(1) hydrogen-bonded
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˚ , o) Table 2 Selected geometric parameters for (I) (A O(1)–C(1)
1.2189(13)
(1.214)*
O(2)–C(1)
1.3126(13)
(1.356)*
O(3)–C(3)
1.4325(14)
(1.415)*
O(3)–C(4)
1.3846(14)
(1.386)*
O(4)–C(2)
1.4226(12)
(1.419)*
O(4)–C(9)
1.3754(14)
(1.387)*
O(1)–C(1)–O(2)
125.37(10)
(116.13)*
O(1)–C(1)–C(2)
123.13(9)
(130.37)*
C(3)–O(3)–C(4)
111.52(8)
(113.55)*
C(2)–O(4)–C(9)
115.56(8)
(114.79)*
O(1)–C(1)–C(2)–C(3)
112.22(12)
(104.08)*
O(2)–C(1)–C(2)–C(3)
-67.00(12)
(-76.57)*
C(1)–C(2)–C(3)–O(3)
-63.06(11)
(-72.93)*
C(1)–C(2)–O(4)–C(9)
87.49(10)
(88.53)*
O(3)–C(3)–C(2)–O(4)
60.05(11)
(53.72)*
C(2)–C(3)–O(3)–C(4)
-54.17(12)
(-42.28)*
˚ , °) [25] * MOPAC computation results (A
Fig. 2 ORTEP drawings of (I) showing the atom numbering scheme of the asymmetric unit and 50% probability displacement ellipsoids of non-H atoms
Table 3 Hydrogen bonds and C–HO weak intermolecular inter˚ and °) actions for (I) (A D–HA
d(D–H)
d(HA)
d(DA)
\(DHA)
O(2)–H(2B)O(1)#1
0.84
1.81
2.6392(12)
171.8
C(3)–H(3A)O(3)#2
0.99
2.58
3.3415(14)
133.3
C(3)–H(3B)O(1)#3
0.99
2.64
3.4628(14)
140.5
C(6)–H(6A)O(1)#4
0.95
2.62
3.5212(17)
158.3
C(7)–H(7A)O(2)#5
0.95
2.62
3.4442(16)
145.3
Symmetry transformations used to generate equivalent atoms #1 1 - x, 2 - y, -z; #2 1 - x, 1 - y, -z; #3 1 - x, - ? y, -z; #4 -x, - ? y, -z; #5 x - 1,-y ? 3/2, z ? 1/2
interaction involving centrosymmetrically related molecules (1 - x, 2 - y, -z) is very strong and stabilizes molecular packing of these dimers into a supramolecular assembly. The dihedral angle between the mean planes of the R22 (8) graph-set motif’s of two adjacent dimers in the unit cell is 75.7(5)°. The mean plane of an R22 (8) graph-set motif makes an angle of 88.4(5)° with the mean plane of the benzene ring in the same dimer and 13.1(2)° or 13.4(7)° with the mean plane of a benzene ring from an adjacent dimer (Figs. 3 and 4). The distance between the centroids of a benzene ring and that of an adjacent nearly parallel
Fig. 3 The molecular packing for (I) viewed down the a axis. Dashed lines indicate intermolecular hydrogen bonds between an array of carboxyl acceptor atoms O(1) and O(2) (O(1)H(2B)–O(2)) which form an R22 (8) graph-set motif arrangement
˚ providing essentially no R22 (8) graph-set motif is 3.67(2) A effect on molecular packing from these groups in the unit cell. Additional C–HO weak intermolecular interactions are observed involving the carboxyl oxygen atom, O(2), [C(7)–H(7A)O(2)] and a dioxane oxygen atom, O(3), [C(3)–H(3A)O(3)]. Each of these links involve hydrogen atoms from nearby benzene [H(7A), 1 - x, -y ? 3/2, z ? 1/2] and dioxane [H(3A), 1 - x, 1 - y, -z] rings, respectively. The second dioxane oxygen atom, O(4), does not participate in any intermolecular bonding activities. The O(1) atom from the carboxyl group is also an acceptor atom for weak intermolecular interactions with H(3B), (C(3)–H(3B)O(1); 1 - x, - ? y, -z), and H(6A), (C(6)–H(6A)O(1); -x, - ? y, -z). Also, the hydrogen bond between the carboxyl acceptor atoms O(1) and O(2) [ i.e. O(1)H(2B)–O(2)] form an R22 (8) graph-set motif [23] which link the molecules into chains along the a axis in the (110) plane of the unit cell (Fig. 4). Details of the hydrogen bonding and weak intermolecular interactions are given in Table 3.
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number of the strong and weak intermolecular hydrogen bonding and p-ring interactions observed.
Supporting Information Available X-ray crystallographic files, in Cif format, for the structure determinations of (I) (697309) has been deposited with the Cambridge Crystallographic Date Center, CCDC: 26091. Copies of this information may be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ (Fax: ?44-1223-336033; email: deposit@ccdc. cam.uk or at: http://www.ccdc.cam.ac.uk). Acknowledgment LM thanks the University of Mysore for use of their research facilities. RJB acknowledges the NSF MRI program (Grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.
References
Fig. 4 The molecular packing for (I) viewed down the c axis. Dashed lines indicate hydrogen bonds between the carboxyl acceptor atoms O(1) and O(2) (O(1)H(2B)–O(2)) which form an R22 (8) graph-set motif arrangement and link the molecules into a supramolecular assembly in the unit cell
The structure is also supported by a C(1)–O(1)Cg2 p-ring interaction at 1 - x, ? y, - z where Cg2 = center of gravity of the benzene ring [C(4)–C(9), ˚ , O(1)Cg2 = 3.613(6) A ˚ , C(1)– C(1)Cg2 = 3.437(6) A O(1)Cg2 = 72.0(0)°]. This interaction provides more weak intermolecular interaction which gives added support to molecular packing stability in the unit cell. After a MOPAC AM1 calculation of the C9H8O4 molecule with WebMO Pro (AM1 Austin Model 1 approximation together with the Hartree-Fock closed-shell restricted wavefunction was used and minimizations were ˚ -1), teminnated at an r.m.s. gradient of \0.01 kJ mol-1 A see [25], the bond lengths, bond angles and torsion angles of the dioxane ring and carboxyl group change significantly altering the half-chair configuration of the ring and compressing the O(1)–C(1)–O(2) angle between the oxygen atom in the carboxyl ring. A comparison of these values to those from the crystal structure is listed in Table 2. It is clear that distortions in the bond distances, bond angles and torsion angles of the dioxane ring and attached carboxyl group are significantly influenced by the strength and
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