Solid-state behaviour of pyridine-2,6-dicarboxylate esters: supramolecular assembly into infinite tapes

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Abstract

In the solid state, diesters of pyridine-2,6-dicarboxylic acid assemble into edge-to-edge, front-to-back associated tapes involving a novel triple supramolecular contact consisting of one N_pyridine⋯H–C_pyridine and two C[double bond, length half m-dash]O⋯H–C_pyridine interactions. This intermolecular contact is robust, proving insensitive to additional interactions involving the side arms, and is also observed when the orientation of the pyridine core is reversed.

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Introduction

Successful crystal engineering of organic materials¹ requires access to a large number of synthons and a detailed understanding of the subtle interplay of relatively weak interactions which can become important in the solid state. Desiraju and others² have described a wide variety of intermolecular contacts which can be used to control the architecture of organic solids. Despite the considerable interest in the use of 2,6-disubstituted pyridines in the organisation of molecular architecture,³ the Cambridge Structural Database⁴ contains only one example of a free pyridine ring bearing an ester functionality at both C-2 and C-6,⁵ and even in that case all other positions about the pyridine ring are also substituted. All other ‘hits’ incorporating the 2,6-dicarboxylato unit are either concerned with situations in which the pyridine ring is part of a macrocyclic skeleton, or cases where strong electrostatic interactions dominate, e.g. in metal-ion complexes⁶ or in the parent diacid and its salts.^4,7 We now report preliminary results of a study of the solid-state behaviour of a number of simple pyridine-2,6-dicarboxylate esters 1a–f and a 3,5-disubstituted analogue 2.

Results and discussion

X-Ray structural studies of a series of symmetrical bis(arylmethyl) pyridine-2,6-dicarboxylates 1a–f reveal that each of these derivatives adopts an extended ‘W’-conformation in the solid state (Fig. 1) in which the carbonyl groups are oriented parallel with the nitrogen lone pair of the pyridine ring. For 1a–d the peripheral benzene rings are twisted in a helical fashion along the long molecular axis relative to the planar core (see Table 1) reflecting the presence of a C₂ symmetry axis [through C(1) and N(1)] whereas in 1e they are twisted in the opposite sense. Of particular interest, however, is the fact that in each case neighbouring molecules appear to associate in a triple C–H⋯X (X⊕=⊕N, O) close contact 3 (see Fig. 1) to form an infinite tape running through the structure.

Fig. 1 Solid-state behaviour of 1b showing the typical extended conformation adopted by individual molecular units of the esters 1a–f and the front-to-back contact geometry with a neighbouring molecule. Click image or 1.htm to access a 3D representation.

Table 1 Contact geometries for the front-to-back association of pyridine diesters 1 and 2 (the various distances and angles being defined in 3)^a

Compound^b	r 1/pm	r 2/pm	ϕ/°	θ/°	ψ/°	Twist^c/°
a In all cases hydrogens were found from Fourier difference maps. b Click on each compound number to access a view of its edge-to-edge dimer. c This represents the degree of twist of the aromatic ring of the side arm relative to the pyridine core.
1aT1.htm	248	248	164	180	127	28.27 (8)
1bT1.htm	250	255	164	180	125	24.67(11)
1cT1.htm	258	252	156	180	129	23.12(30)
1dT1.htm	266	261	151	180	128	23.58(19)
1eT1.htm	251/247	252	158/170	177	127/125	24.80(12)/22.94(8)
1fT1.htm	253	268	166	180	133	—
2T1.htm	255	258	156	180	133	21.82(16)

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This three-point intermolecular contact is somewhat reminiscent of those previously described by Biradha et al.⁸ but, in the present example, is constrained by the molecular architecture into a less-favourable geometry (through the angular nature of the C–H⋯O contacts). The tapes stack in a face-to-face manner with long molecular axis neighbours assembled in either a parallel [1a, 1b, 1e as in Fig. 2(i)] or a herringbone (1c, 1d) fashion [Fig. 2(ii)]. The geometries of the intermolecular contacts are summarised in Table 1, contact distances lying within the range of those previously reported⁸ (it should be noted that in each case the pyridine ring hydrogen atoms were located using Fourier difference maps). Indeed, the N_pyridine⋯H–C_aromatic contact distances r₂ reported in Table 1 are similar to those reported by Bishop and co-workers in edge-to-edge associated quinoline dimers.⁹

Fig. 2 (i) End view of the tapes showing parallel packing of tapes such as 1b. Click image or 2i.htm to access a 3D representation. (ii) End view of the tapes showing the herringbone packing of tapes like 1d. Click image or 2ii.htm to access a 3D representation.

One issue to be addressed concerns whether the molecular packing observed simply arises from the two-fold symmetry present in these structures. However, despite the fact that no such crystallographic symmetry is present in the fluorobenzyl derivative 1e the same solid-state behaviour is present. Secondly, in order to test whether the observed architecture is caused by aromatic face-to-face association, we have examined the solid-state behaviour of the simple aliphatic ester analogue 1f. Once again the molecules form extended tapes involving the triple contact shown in Fig. 1 demonstrating the favourable nature of this contact. It should also be noted that the bromo and chloro esters, 1c and 1d, respectively, are isostructural whereas the benzyl ester 1a and 4-methylbenzyl ester 1b are isometric.¹⁰

The herringbone stacking observed in the bromo and chloro derivatives 1c and 1d results in close interhalogen van der Waals' contacts¹¹ with geometries¹² typical of those previously observed for unsymmetrical interhalogen interactions.¹³ As expected, no such association is observed for the fluoro derivative 1e which adopts a parallel-stacked architecture instead.¹⁴

In order to test further the robust nature of the triple contact 3 we have explored the effect of reversing the orientation of the pyridine core as in 2. This should weaken the association by introducing secondary repulsive diagonal interactions between the pyridine nitrogen lone pair and those on the carbonyl groups (by moving from a DDD–AAA contact to a DAD–ADA motif; D⊕=⊕donor, A⊕=⊕acceptor).¹⁵ Nonetheless the ester 2 still forms an extended tape. (Click str2.htm to access a 3D representation.)

The formation of the triple contact 3 by each of the esters 1a–f suggests that the β- and γ-hydrogens of the core pyridine ring [attached to C(2) and C(1) respectively – see Fig. 1] must be quite acidic. Some support for this is provided by chemical shift data for these diesters which show a significant downfield shift for these protons compared with the chemical shifts of equivalent sites in saturated analogues such as those in 2,6-bis(hydroxymethyl)pyridine,¹⁶ with the shift for the β-hydrogen being particularly affected by the presence of the neighbouring ester function.

Whilst the geometric constraints present in the front-to-back contact necessarily impose less than optimum C–H⋯O contact geometries in the triple contact reported here, the generality of this interaction, regardless of the nature of the sidearms present in 1a–f, leads us to the inevitable conclusion that this is a potentially useful solid-state synthon. We are currently carrying out detailed spectroscopic studies on the pyridyl diesters 1a–f and 2 in order to gain further insight into the nature of the intermolecular contacts reported here and are exploring ways of exploiting this assembly process for the development of functional materials.

Experimental

All seven diesters were readily prepared by reaction of 2,6-bis(chlorocarbonyl)pyridine with the appropriately substituted alcohol in the presence of Et₃N/CH₂Cl₂.

Bis(benzyl) pyridine-2,6-dicarboxylate 1a: mp 119 °C from acetone (Anal. calc. for C₂₁H₁₇NO₄: C: 72.61, H: 4.93, N: 4.03. Found: C: 72.62, H: 4.87, N: 3.89%); ν_max/cm⁻¹: 1752 (C[double bond, length half m-dash]O); m/z (ES⁺) 348 (M⊕+⊕H⁺); δ_H (CDCl₃): 8.27 (2H, d, J 8.0 Hz), 7.98 (1H, t, J 8.0 Hz), 7.50 (4H, d, J 7.5 Hz), 7.37 (5H, m), 5.45 (4H, s).

Bis(4-methylbenzyl) pyridine-2,6-dicarboxylate 1b: mp 149 °C from acetone (Anal. calc. for C₂₃H₂₁NO₄: C: 73.57, H: 5.64, N: 3.73. Found: C: 73.51, H: 5.53, N: 3.69%); ν_max/cm⁻¹: 1750 (C[double bond, length half m-dash]O); m/z (ES⁺) 366 (M⊕+⊕H⁺); δ_H (CDCl₃): 8.25 (2H, d, J 8.0 Hz), 7.96 (1H, t, J 8.0 Hz), 7.38 (4H, d, J 8.0 Hz), 7.18 (4H, d, J 8.0 Hz), 5.41 (4H, s), 2.30 (6H, s).

Bis(4-bromobenzyl) pyridine-2,6-dicarboxylate 1c: mp 177 °C from acetone (Anal. calc. for C₂₁H₁₅Br₂NO₄: C: 49.91, H: 2.99, N: 2.77. Found: C: 50.04, H: 2.83, N: 2.77%); ν_max/cm⁻¹: 1744 (C[double bond, length half m-dash]O); m/z (ES⁺) 408 (M⊕+⊕H⁺); δ_H (CDCl₃): 8.25 (2H, d, J 8.0 Hz), 7.98 (1H, t, J 8.0 Hz), 7.48 (4H, d, J 8.0 Hz), 7.34 (4H, d, J 8.5 Hz), 5.35 (4H, s).

Bis(4-chlorobenzyl) pyridine-2,6-dicarboxylate 1d: mp 161–163 °C from CH₂Cl₂/light petroleum (Anal. calc. for C₂₁H₁₅Cl₂NO₄: C: 60.59, H: 3.63, N: 3.36, Cl, 17.03. Found: C: 60.60, H: 3.43, N: 3.23, Cl, 16.77%); ν_max/cm⁻¹: 1736 (C[double bond, length half m-dash]O); m/z (ES⁺) 416 (M⊕+⊕H⁺); δ_H (CDCl₃) 8.27 (2H, d, J 7.5 Hz), 7.98 (1H, t, J 8.0 Hz), 7.42 (4H, d, J 8.5 Hz), 7.37 (4H, d, J 8.5 Hz), 5.41 (4H, s).

Bis(4-fluorobenzyl) pyridine-2,6-dicarboxylate 1e: mp 108 °C from acetone (Anal. calc. for C₂₁H₁₅F₂NO₄: C: 65.80, H: 3.94, N: 3.65. Found: C: 65.54, H: 4.02, N: 3.49%); ν_max/cm⁻¹: 1744 (C[double bond, length half m-dash]O); m/z (ES⁺) 384 (M⊕+⊕H⁺); δ_H (CDCl₃) 8.2 (2H, d, J 8.03 Hz), 7.9 (1H, t, J 8.0 Hz), 7.4 (4H, dd, J 5.5, 8.5 Hz), 6.8 (4H, dd, J 8.5, 2.0 Hz), 5.3 (4H, s).

Bis(butyl) pyridine-2,6-dicarboxylate 1f: mp 64 °C (lit.¹⁷ 63–64 °C) from acetone; ν_max/cm⁻¹: 1728 (C[double bond, length half m-dash]O); m/z (ES⁺) 280 (M⊕+⊕H⁺); δ_H (CDCl₃) 8.25 (2H, d, J 8.0 Hz), 7.98 (1H, t, J 8.0 Hz), 7.38 (4H, d, J 8.0 Hz), 7.18 (4H, d, J 8.0 Hz), 4.41 (4H, t, J 7.0 Hz), 1.81 (4H, tt, J 7.0, 8.0 Hz), 1.48 (4H, qt, J 7.5, 8.0 Hz), 0.97 (6H, t, J 7.5 Hz).

Bis(4-nitrobenzyl) pyridine-3,5-dicarboxylate 2: mp 180 °C from acetone (Anal. calc. for C₂₁H₁₅N₃O₈: C: 57.67, H: 3.46, N: 9.61. Found: C: 57.73, H: 3.33, N: 9.48%); ν_max/cm⁻¹: 1731 (C[double bond, length half m-dash]O); m/z (ES⁺) 406 (M⊕+⊕Na⁺); δ_H (CDCl₃) 9.35 (2H, d, J 2.5 Hz), 8.85 (1H, t, J 2.0 Hz), 8.25 (4H, d, J 8.5 Hz), 7.55 (4H, d, J 8.5 Hz), 5.50 (4H, s).

Crystallographic data collection and structure determination

Single crystal X-ray analyses were carried out using a Nonius Kappa CCD diffractometer and Nonius FR591 rotating anode X-ray generator. The structures were solved using WinGX¹⁸ and refined using SHELX-97.¹⁹ In view of their role in the structures reported, the pyridine hydrogens in each structure were found from Fourier difference maps, all other hydrogens being fixed. Brief details of each structure solution are summarised in Table 2 and full details are available with the supplementary data.

Table 2 Crystallographic data for compounds 1a–f and 2^a

Parameter	1a	1b	1c	1d	1e	1f	2
a Click b107221h.txt for full crystallographic data (CCDC 169118–169124).
Empirical formula	C21H17NO4	C23H21NO4	C21H15Br2NO4	C21H15Cl2NO4	C21H15F2NO4	C15H21NO4	C21H15N3O8
M	347.36	375.41	505.16	832.48	383.34	279.33	437.36
Crystal system	Monoclinic	Monoclinic	Orthorhombic	Orthorhombic	Triclinic	Monoclinic	Orthorhombic
Space group	C2/c	C2/c	P21212	P21212	P1̄	C2/c	P21212
a/Å	31.972(6)	34.730(7)	31.827(6)	31.705(6)	6.3010(10)	23.805(5)	30.518(6)
b/Å	6.2670(10)	6.2950(10)	4.7360(10)	4.6550(10)	7.2690(10)	6.3340(10)	4.8630(10)
c/Å	8.396(2)	8.758(2)	6.2970(10)	6.2620(10)	20.518(4)	10.104(2)	6.2670(10)
α/°	90	90	90	90	80.04(3)	90	90
β/°	91.18(3)	103.69(3)	90	90	83.50(3)	99.81(3)	90
γ/°	90	90	90	90	69.79(3)	90	90
V/Å^3	1681.9(6)	1860.3(6)	949.2(3)	924.2(3)	867.2(2)	1501.2(5)	930.1(3)
Z	4	4	2	2	2	4	2
T/K	150	150	150	293	150	150	150
R 1	0.0528	0.0483	0.0307	0.0560	0.0561	0.0603	0.0538
wR 2	0.0914	0.1357	0.0803	0.1415	0.1110	0.1306	0.0968
Unique data [I⊕>⊕2σ(I)]	1876	1279	1040	1799	3571	1558	2059

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Supporting information available

Tables of fractional atomic co-ordinates, selected interatomic distances, bond and torsion angles, and anisotropic temperature factors for compounds 1a–f and 2 together with additional figures showing Ortep plots and the numbering scheme used for the structure solutions. Click esi.pdf to access information.

Acknowledgements

Thanks are due to Professor M. B. Hursthouse and the EPSRC National Crystallographic Service (Chemistry Department, University of Southampton) for help with the X-ray data collection and structure solutions and to EPSRC for studentships (to J. R. G., P. N. H., D. A. S. M. and R. A. P.). We also wish to acknowledge the use of the EPSRC's Chemical Database Service at Daresbury.

Notes and references

1. G. R. Desiraju and C. V. K. Sharma, in The Crystal as a Supramolecular Entity, Perspectives in Supramolecular Chemistry, ed. G. R. Desiraju, Wiley, Chichester, 1996, ch. 2, pp. 31–61; G. R. Desiraju and T. Steiner, The Weak Hydrogen Bond, Oxford University Press, Oxford, 1999.
2. See, for example: G. R. Desiraju, Chem. Commun., 1997, 1475; G. R. Desiraju, Angew. Chem., Int. Ed. Engl., 1995, 34, 2311; M. D. Zaman, M. Tomura and Y. Yamashita, Chem. Commun., 1999, 999; J. C. MacDonald, P. C. Dorrestein, M. M. Pilley, M. M. Foote, J. L. Lundburg, R. W. Henning, A. J. Schultz and J. L. Manson, J. Am. Chem. Soc., 2000, 122, 11 692.
3. F. J. Carver, C. A. Hunter and R. J. Shannon, J. Chem. Soc., Chem. Commun., 1994, 1277; M. C. Grossel, D. G. Hamilton, P. N. Horton, S. Neveu, R. A. Parker and P. S. Walker, Synthesis, 1998, 78.
4. The United Kingdom Chemical Database Service, D. A. Fletcher, R. F. McMeeking and D. Parkin, J. Chem. Inf. Comput. Sci., 1996, 36, 746.
5. D. L. Boger, J. Hong, M. Hikota and M. Ishida, J. Am. Chem. Soc., 1999, 121, 2471 . This structural study is of 3-(3′,5′-dinitrobenzyloxycarbonyl)-4,5-dimethoxy-2,6-bis(methoxycarbonyl)pyridine (Refcode: HOSPAG) in which crowding around the pyridine ring prevents any useful conclusions being drawn about the behaviour of ‘simple’ pyridine-2,6-dicarboxylate esters.
6. H. Tsukube, S. Shinoda, J. Uenishi, T. Hiraoka, T. Imakoga and O. Yonemitsu, J. Org. Chem., 1998, 63, 3884; G. H. Singh and D. B. Sowerby, J. Chem. Soc., Dalton Trans., 1977, 490; F. Renard, C. Piguet, G. Bernardinelli, J.-C. G. Bünzli and G. Hopfgartner, Chem.-Eur. J., 1997, 3, 1660.
7. Of the 178 hits obtained, 21 related to macrocyclic structures and the remainder to structures incorporating the pyridine-2,6-dicarboxylato fragment as the free diacid or its salts, or in metal complexes.
8. K. Biradha, C. V. K. Sharma, K. Panneerselvam, L. Shimoni, H. L. Carrell, D. E. Zacharias and G. R. Desiraju, J. Chem. Soc., Chem. Commun., 1993, 1473.
9. C. E. Marjo, M. L. Scudder, D. C. Craig and R. Bishop, J. Chem Soc., Perkin Trans. 2, 1997, 2099; S. F. Alshahateet, R. Bishop, D. C. Craig and M. L. Scudder, CrystEngComm, 2001, 25.
10. A. Kalman, L. Parkanyi and G. Argay, Acta Crystallogr., Sect. B, 1993, 49, 1039.
11. O. Navon, J. Bernstein and V. Khodorkovsky, Angew. Chem., Int. Ed., 1997, 36, 601.
12. In the present study the following contact geometries are observed: for 1c: d_Br–Br⊕=⊕3.61 Å with angles θ(C₁–Br–Br)⊕=⊕99.1, θ(C₂–Br–Br)⊕=⊕166.7°; for 1d: d_Cl–Cl⊕=⊕3.55 Å, θ(C₁–Cl–Cl)⊕=⊕98.5, θ(C₂–Cl–Cl)⊕=⊕166°; for 1e: d_F–F⊕=⊕3.16 Å, θ(C₁–F–F)⊕=⊕100.3, θ(C₂–F–F)⊕=⊕171.2°.
13. T. Sakurai, M. Sundaralingam and G. A. Jeffrey, Acta Crystallogr., 1963, 16, 354; N. Ramasubbu, P. Parthasarathy and P. Murray-Rust, J. Am. Chem. Soc., 1986, 108, 4308.
14. P. Murray-Rust, W. C. Stallings, C. T. Monti, R. K. Preston and J. P. Glusker, J. Am. Chem. Soc., 1983, 105, 3206.
15. J. Pranata, S. G. Wierschke and W. L. Jorgensen, J. Am. Chem. Soc., 1991, 113, 2810; T. J. Murray and S. C. Zimmerman, J. Am. Chem. Soc., 1992, 114, 4010.
16. For 2,6-di(hydroxymethyl)pyridine the pyridyl protons appear at δ 7.15 (H₃/H₅) and 7.70 (H₄) ppm. Therefore in the diesters the corresponding protons are deshielded by ca. 1.1 ppm (H_3/5) and by ca. 0.3 ppm (H₄), respectively.
17. A. El-ghayoury and R. Ziessel, Tetrahedron Lett., 1998, 39, 4473.
18. L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837.
19. G. M. Sheldrick, SHELX-97, Program for Crystal Structure Analysis (Release 97-2), Institut für Anorganische Chemie der Universität, Tammanstrasse 4, D-3400 Göttingen, Germany, 1998.

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