Role of the Molecular Conformation in the Two-and Three

Apr 3, 2007 - Sánchez 2, E-38206 La Laguna, Tenerife, Spain, and Instituto de Investigaciones Químicas, CSIC, Américo Vespucio s/n, Isla de la Cart...
0 downloads 0 Views 358KB Size
CRYSTAL GROWTH & DESIGN

Role of the Molecular Conformation in the Two- and Three-Dimensional Supramolecular Structure of 10 Hydroxyl-N-alkylamides Concepcio´n Foces-Foces,*,† Matı´as Lo´pez-Rodrı´guez,‡ Cirilo Pe´rez,‡ Julio D. Martı´n,# and Natalia Pe´rez-Herna´ndez*,#

2007 VOL. 7, NO. 5 905-911

Departamento de Cristalografı´a, Instituto de Quı´mica-Fı´sica ‘Rocasolano’, CSIC, Serrano 119, E-28006 Madrid, Spain, Instituto de Bioorga´ nica, UniVersidad de La Laguna-CSIC, AVenida Astrofı´sico Fco. Sa´ nchez 2, E-38206 La Laguna, Tenerife, Spain, and Instituto de InVestigaciones Quı´micas, CSIC, Ame´ rico Vespucio s/n, Isla de la Cartuja, E-41092 SeVilla, Spain ReceiVed October 3, 2006; ReVised Manuscript ReceiVed February 10, 2007

ABSTRACT: Sixteen new 7,7-dialkyl-5-hydroxymethyl-6-oxabicyclo[3.2.1]octane-1-carboxylic acid amide derivatives with the hydroxymethyl and the N-alkylamide functional groups in axial positions have been synthesized, and the solid-state structure of 10 of them has been determined. All of them crystallized as anhydrous compounds, and the conformation of the hydroxyl and N-alkylamide substituents was found to be correlated with the types of interactions in which they are involved, generating two- and three-dimensional hydrogen-bonding networks based on identical dimeric substructures in 8 of the 10 cases. This dimer can be considered as a supramolecular synthon for future crystal engineering studies. Introduction As part of our structural studies on the inclusion of water molecules into the hydrogen-bonding pattern of condensed organic materials, we have carried out the synthesis and the analysis of the crystal structure of a family of bridged oxacyclic molecules with axially oriented hydroxy-N-alkylamide substituents (1, Chart 1). We previously reported that compounds possessing axially oriented hydroxy-carboxylic1 acid or dicarboxylic acid2 functions (2, 3 in Chart 1) might create hydrated or anhydrous hydrogenbonding patterns on the exclusive basis of the structure of the molecular components. Thus, in the hydroxy-carboxylic acid family, only the homologue possessing ethyl appendages (2, R2 ) ethyl), crystallizes in both anhydrous and hydrated forms. In the studied diacid series, it appears that to maintain the hydrated array the volume corresponding to the cyclopropyl substituent (3, R2 ) cyclopropyl) is approximately the maximum allowed. Larger appendages provide anhydrous packing.3 In this family 3, only the homologue, where R2 ) cyclopropyl, crystallizes in both hydrated and anhydrous forms. The new hydroxy-N-alkylamide family 1 was selected because the molecular structure maintains the same unbalanced hydrogen-bond donor/acceptor ratio as in the previously studied families 2 and 3 and offers the possibility of a large variety of potential intermolecular interactions. A wide range of homologues was synthesized by changing the number and nature of selected atoms in both the alkyl appendages at the oxolane ring and in the N-alkylamide function (1a-1p, Chart 2), and their structural influence in the solid state was studied. * To whom correspondence should be addressed. (C.F.-F.) Tel:+34/91/ 5619400 ext. 1103; fax.:+34/91/5642431; e-mail: [email protected]; (N.P.-H.) Present address: Institut fu¨r Chemie, Freie Universita¨t Berlin, Takustrasse 3, 14195-Berlin, Germany. Tel: +49/30/83855472; fax: +49/ 30/83855310; e-mail: [email protected]. † Departamento de Cristalografı´a, Instituto de Quı´mica-Fı´sica ‘Rocasolano’, CSIC. ‡ Instituto de Bioorga ´ nica, Universidad de La Laguna-CSIC. # Instituto de Investigaciones Quı´micas, CSIC.

Chart 1.

Chart 2.

Chemical Diagram of the Three Related Families of Compounds

Chemical Diagram of the Studied Hydroxyl Amides

Experimental Section Each component of family 1 was prepared from its corresponding hydroxy-carboxylic acid. We have undertaken the preparation of 16 hydroxy-amides (compounds 1a-1p, Chart 2) by reaction of four different synthesized hydroxy-acids with four different commercial amines (methylamine, ethylamine, propylamine, and benzylamine). The general method for the synthesis of the amides is as follows: in a typical experiment, the hydroxy-acid with ethyl appendages (51.0 mg, 0.21 mmol, 1.0 equiv), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (119.0 mg, 0.62 mmol, 3.0 equiv), 3-hydroxybenzotriazole hydrate (84.0 mg, 0.62 mmol, 3.0 equiv), and triethylamine (51.0 µL, 0.37 mmol, 1.8 equiv), was dissolved in dichloromethane (2.5 mL). After the addition of the triethylamine, the slightly cloudy solution became completely transparent. At this moment, ethylamine was bubbled during 10 min through the stirred solution (in the case of liquid amines, 2.5 equiv were added via syringe at this moment), and the reaction was kept 12 h under argon to ensure completion. After this

10.1021/cg060671u CCC: $37.00 © 2007 American Chemical Society Published on Web 04/03/2007

906 Crystal Growth & Design, Vol. 7, No. 5, 2007

Foces-Foces et al.

Table 1. Crystal Data and Selected Refinement Parameters at 170 Ka identification code crystal data/parameter

1a

1d

1e

1f

1g

alkyl substituents at C9 alkyl substituents at N1 empirical formula formula weight crystal system space group a (Å) b (Å) c (Å) R (°) β (°) γ (°) volume (Å3) Z density (calculated) (g/cm3) theta max (°) data/restraints/parameters final R and Rw [I > 2σ(I)] largest diff peak /hole(e Å-3)

methyl methyl C12H21NO3 227.30 monoclinic P21/c 10.6102(3) 16.4684(4) 13.9943(5) 90 93.248(1) 90 2441.3(1) 8 1.237 27.5 5562/0/313 0.071, 0.185 0.404/ -0.362

methyl benzyl C18H25NO3 303.39 monoclinic I2/a 23.7440(7) 11.9580(3) 24.2389(8) 90 91.506(2) 90 6879.8(3) 16 1.172 25.0 6000/0/399 0.080, 0.213 0.496/ -0.498

ethyl methyl C14H25NO3 255.35 monoclinic P21/c 15.566(16) 8.685(20) 21.402(22) 90 93.521(7) 90 2888(8) 8 1.175 27.5 6481/0/328 0.063, 0.142 0.350/ -0.295

ethyl ethyl C15H27NO3 269.38 monoclinic P21/c 15.623(3) 9.0320(16) 21.497(11) 90 93.831(16) 90 3026.6(18) 8 1.182 27.5 6780/0/346 0.064, 0.163 0.462/ -0.372

ethyl n-propyl C16H29NO3 283.40 triclinic P1h 9.6670(2) 12.7750(3) 14.0170(4) 87.533(2) 89.161(1) 69.512(1) 1620.04(7) 4 1.162 27.5 7427/6/394 0.087, 0.202 0.898/ -0.604

crystal data/parameter

1h

1i

1j

1n

1p

alkyl substituents at C9 alkyl substituents at N1 empirical formula formula weight crystal system space group a (Å) b (Å) c (Å) R (°) β (°) γ (°) volume (Å3) Z density (calculated) (g/cm3) theta max (°) data/restraints/parameters final R and Rw [I > 2σ(I)] largest diff peak /hole (e Å-3)

ethyl benzyl C20H29NO3 331.44 tetragonal I41/a 24.332(6) 24.332(6) 12.343(8) 90 90 90 7308(6) 16 1.205 25.0 3211/0/219 0.096, 0.238 0.424/-0.287

n-propyl methyl C16H29NO3 283.40 triclinic P1h 9.320(22) 14.022(16) 13.882(19) 67.059(14) 78.226(53) 80.884(35) 1629(5) 4 1.155 28.6 8108/0/363 0.056, 0.147 0.344/-0.207

n-propyl ethyl C17H31NO3 297.43 orthorhombic Pbca 10.2370(2) 16.0770(4) 21.1550(6) 90 90 90 3481.7(2) 8 1.135 27.5 3988/0/191 0.069, 0.182 0.651/-0.807

cyclopropyl ethyl C17H27NO3 293.40 tetragonal I41/a 24.6660(5) 24.6660(5) 10.5550(4) 90 90 90 6421.8(3) 16 1.214 27.5 3676/0/192 0.084, 0.209 0.635/-0.610

cyclopropyl benzyl C22H29NO3 355.46 orthorhombic Pna21 15.3900(17) 10.7790(17) 23.333(10) 90 90 90 3871(2) 8 1.220 27.5 4519/7/471 0.073, 0.173 0.679/-0.534

identification code

a

Crystallographic numbering scheme in Figure 1.

time, the practical disappearance of the starting material was confirmed by thin layer chromotography (TLC). Saturated aqueous NaHCO3 solution was added (2.0 mL), and the basic reaction was extracted, with the aim of separating the possible remaining starting hydroxyacid as a carboxylate in the aqueous phase. After that, the organic phase was treated with aqueous HCl solution (3%), until neutralization, and again it extracted with dichloromethane (2.0 mL). Finally, the organic phase was washed with saturated aqueous NaCl solution (2.0 mL) and dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the pure product (45.0 mg, 0.16 mmol, 80% yield), which was crystallized using a small amount of acetone to dissolve it in CCl4. Acetone was afterward removed by evaporation in a water bath; in this way, the flask is simultaneously exposed to moisture. In the case of compounds 1a and 1b, the extraction was achieved with ethyl acetate due to the high polarity of the products. Even so, a fraction of them was retained in the aqueous phase. The concentrated residue was washed with CHCl3 and filtered, to separate the amides (very soluble in CHCl3) from 3-hydroxy-benzotriazole hydrate (less soluble). These products were directly crystallized using the same conditions as described above, exactly the same as the ones used for the related compound families 2 and 3. Analytical data for all compounds can be found as Supporting Information. X-ray Analysis. Crystals of 10 (1a, 1d-1j, 1n, 1p) out of the 16 synthesized compounds were suitable for the X-ray analysis. The intensity data for all compounds were recorded on a Nonius Kappa CCD diffractometer4 (λ(MoKR) ) 0.7107 Å) driven by DENZO and

COLLECT software.5 All structures were solved by direct methods6 and refined based on F2 using SHELX97,7 both programs operating under the WinGx program package.8 Data for all compounds were collected at room temperature and at 170 K. After confirmation that there was no phase transition, only data at 170 K were retained. The homogeneity of the material as well as the polymorphism was assessed by checking the cell dimensions and symmetry of several samples for each case. All hydrogen atoms were located on difference Fourier maps and were allowed to ride on the respective bonded atoms. Crystal data and selected refinement parameters are given in Table 1. The unit cell dimensions and symmetry indicated that 1e is isomorphous with 1f and 1h is isomorphous with 1n. The corresponding asymmetric units were selected so that the atomic coordinates of the common atoms were approximately the same. Moreover, 1d is pseudoisomorphous with the pair 1h, 1n since the symmetry of the spectrum is 2/m instead of 4/m with the 2- and 4-fold axis along the b-axis in 1d and along c in 1h, 1n, respectively (Table 1). In the 1d structure, the loss of symmetry is compensated by the presence of two independent molecules that, due to their relative disposition plus those generated by a 2-fold screw axis, give rise to a pseudo 4-fold screw axis, which is a crystallographic one in 1h and 1n. Disorder over two positions has been observed in the following compounds: in 1a the hydroxyl group, in 1g the ethyl group, and in 1p the propyl groups plus one cyclopropyl ring. Crystallographic information has been deposited in CIF format (CCDC reference numbers 601071-601080). Structural illustrations have been drawn with PLATON9 under WinGx.

Supramolecular Structure of Hydroxyl-alkylamides

Crystal Growth & Design, Vol. 7, No. 5, 2007 907 Table 3. Intermolecular Hydrogen-Bond Geometry (Å and deg)a compd

D-H‚‚‚A (symmetry code)

D‚‚‚A (Å)