Journal of Crystallography

Journal of Crystallography / 2014 / Article

Research Article | Open Access

Volume 2014 |Article ID 371629 |

Pierre Baillargeon, Tommy Lussier, Yves L. Dory, "Hydrogen Bonds between Acidic Protons from Alkynes (C–H···O) and Amides (N–H···O) and Carbonyl Oxygen Atoms as Acceptor Partners", Journal of Crystallography, vol. 2014, Article ID 371629, 5 pages, 2014.

Hydrogen Bonds between Acidic Protons from Alkynes (C–H···O) and Amides (N–H···O) and Carbonyl Oxygen Atoms as Acceptor Partners

Academic Editor: Leonard MacGillivray
Received10 Sep 2013
Revised21 Nov 2013
Accepted10 Dec 2013
Published12 Jan 2014


Crystals of tert-butyl (2S)-2-(prop-2-yn-1-ylcarbamoyl)pyrrolidine-1-carboxylate (Boc-L-Pro-NHCH2CCH) have been obtained. The title compound crystallizes easily as sharp needles in orthorhombic system, space group P 21 21 21 with a = 9.2890(2), b = 9.7292(2), c = 15.7918(4) Å, V = 1427.18(6) Å3, and Z = 4. The main feature of the structure is the orientation of the carbamate and amide. Their dipoles add up and the molecule displays an electric dipole moment of 5.61 D from B3LYP/6-31G(d) calculations. The antiparallel H bonding of amides and the alignment of dipoles induce columnar stacking (the dipole moment along the columnar a axis is 4.46 D for each molecule). The other components across the other axes are, therefore weaker, (3.17 D and 1.23 D along the b and c axes, resp.). The resulting anisotropic columns pack side by side, in an antiparallel fashion mostly by (alkyne) CH···O=C (carbamate) interactions.

1. Introduction

The design of organic solid (crystal or supramolecular engineering) is still today challenging and of great importance [1, 2]. Understanding the details of weak intermolecular interactions plays definitely a major role in the rational design of ordered organic crystals. In our lab, we already achieved great molecular macroscopic order with specially designed peptides, macrocycles as precursors to organic nanotubes [35] or supramolecular walls [6]. Here, we present the crystal structure of the proline derivative 1 (Figure 1) which alkyne, amide, and carbamate functionalities are all involved in hydrogen bonding.

2. Materials and Methods

2.1. Synthesis

To Boc-L-proline N-hydroxysuccinimide ester (2.0 g, 6.4 mmol) in CH2Cl2 (40 mL) was added, at 0°C, propargylamine (0.46 g, 8.4 mmol) and K2CO3 (1.43 g, 10.3 mmol). The reaction mixture was allowed to warm up to RT and was stirred for 72 h. Water (30 mL) was added and the organic phase was isolated. The remaining aqueous layer was extracted again with CH2Cl2 ( mL). The combined organic layers were filtrated through a cotton plug and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel, eluted with Et2O/Hexane (75 : 25), to yield the title product as a white solid (1.654 g, 78%).

(Et2O/Hexane 75 : 25); Tfus (108–111°C); IR (NaCl,   cm−1): 3242, 3055, 2982, 2288, 2117, 1688, 1536, 1402, 1324, 1258, 919, 885, and 718. NMR1H (300 MHz, CDCl3, δ ppm): 6.20 (br, 1H), 4.30–3.90 (m, 3H), 3.50–3.30 (m, 2H), 2.40–2.00 (m, 2H), 2.20 (brs, 1H), 2.00–1.80 (m, 2H), and 1.45 (s, 9H); HRMS (): calcd for C13H20N2O3Na [MNa+]: 275.1366, found: 275.1367.

2.2. X-Ray Crystallography

A dilute CDCl3 solution of 1 (Figure 1) was left to stand in a small vial (partially screwed lid) at room temperature for several days. The alkyne 1 started crystallizing and the vial was kept until nearly complete evaporation of the solvent.

A colorless crystalline needle with approximate dimensions of  mm3 was mounted on a Bruker AXS P4/SMART 1000 CCD diffractometer. The determination of unit cell parameters and data collections were performed with Cu-Kα radiation ( Å). A total of 8432 frames were collected. The total exposure time was 4.68 hours. The frames were integrated with the Bruker SAINT software package using a narrow-frame algorithm. The integration of the data using an orthorhombic unit cell yielded a total of 25149 reflections to a maximum θ angle of 70.03° (0.82 Å resolution), of which 2670 were independent (average redundancy: 9.419, completeness = 98.4%, %, %) and 2655 (99.44%) were greater than (). The final cell constants of  Å,  Å,  Å, volume = 1427.18(6) Å3 and are based upon the refinement of the -centroids of 9807 reflections above 20 with . Data were corrected for absorption effects using the multiscan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.900. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.7575 and 0.8531. The structure was solved and refined using the Bruker SHELXTL software package, using the space group P 21 21 21, with for the formula unit, C13H20N2O3. The final anisotropic full-matrix least-squares, refinement on with 166 variables converged at %, for the observed data and for all data. The goodness of fit was 1.035. The largest peak in the final difference electron density synthesis was 0.196 e3 and the largest hole was −0.151 e3 with an RMS deviation of 0.028 e3. On the basis of the final model, the calculated density was 1.174 g/cm3 and , 544 e. The crystal data, intensity collection conditions, and refinement parameters are presented in Table 1. All crystallographic data for this paper are deposited with the Cambridge Crystallographic Data Centre (CCDC-906056). The data can be obtained free of charge at (or from Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK e-mail: See CIF file in Supplementary Material available online at

CCDC No906056
Empirical formulaC13H20N2O3
Formula weight252.31
Temperature100 K
Wavelength1.54178 Å Cu
Crystal system, space groupOrthorhombic, P 21 21 21
Unit cell dimensions  Å  Å
Volume  Å3
Z, calculated density4, 1.174 Mg/m3
Absorption coefficient 0.684 mm−1
Absorption correctionMultiscan
Max. and min. transmission0.85 and 0.77
Crystal size  mm
range for data collection5.53 to 70.03°
Index ranges , ,
Reflections collected/unique25149/2670 ( )
Refinement methodFull-matrix least squares on
Completeness to theta = 25.00°98.4%
Goodness of fit on 1.035
Final R indices ,
R indices (all data) ,
Largest diff. peak and hole0.196 and −0.151 e·Å−3

3. Results and Discussion

The main feature of the crystal structure of the title compound Boc-L-Pro-NHCH2CCH 1 is the columnar architecture and the orientation of the carbamate, amide, and alkyne groups (Figure 2). From B3LYP/6-31G(d) calculations, the electric dipole moment has a total theoretical value of 5.61 D, with a major contribution (4.46 D) along the axis (which is nearly the orientation of both carbonyl groups). The other components across the other axes are, therefore, weaker (3.17 D and 1.23 D along the and axes, resp.). As expected, both nearly parallel carbonyls act as hydrogen bond acceptors toward the same NH group of a neighboring molecule. Between two consecutive molecules, the NHO=C (amide) and NHO=C (carbamate) distances are 2.218 Å and 3.141 Å, respectively (corresponding to 2.97 Å and 3.58 Å between N and O atoms). Therefore, the contribution of the carbamate carbonyl appears to be less important than that of the amide. This is also confirmed in the alignment of the corresponding carbonyls with the amide N–H groups. Thus, the C=OH(N) angles assume values of 141° and 79° for the amide and the carbamate, respectively. The latter being very distorted is accordingly much weaker than the former [7]. Finally, the linear terminal alkyne groups are disposed nearly perpendicularly to the polar column.

Columns are directly linked to one another by (alkyne) CHO=C (carbamate) interactions (Figure 3) [8, 9]. Although the hydrogen bond character of the CHO interaction has been a subject of controversy [10, 11], CHO hydrogen bonds are now well accepted by the scientific community [1215], especially hydrogen bonds formed by terminal acetylenes where the C–H groups can act as weak hydrogen bond donors owing to their relatively high acidity [8].

The preference for linearity is the main structural feature distinguishing hydrogen bonds from van der Waals interactions [7]. In our case, the angle (CHO angle) is near linearity with a value of 161.61° (Figure 4). This compares well with the known mean value for C(sp)HO angle of 152° [8, 13, 14]. Also, the distance between the terminal alkyne C atom and the carbonyl O atom (3.100 Å) observed in the crystal of 1 is relatively short compared to the literature mean value (3.31 and 3.46 Å) obtained from crystallographic database studies [8, 12].

Finally, when we look along the axis (Figure 5), the columns pile side by side through weak van der Waals noncovalent interactions. The closest distance between H atoms of the t-Bu group is 2.565 Å, which is slightly above the expected vdW radii.

4. Conclusions

In conclusion, the crystal structure of the proline alkyne derivative 1 is dominated by three different interactions of different strengths: (1) hydrogen bonds between amides partners and mostly oriented parallel to the axis, (2) hydrogen bonds between carbonyl oxygen atoms and slightly acidic alkyne hydrogen, whose orientation lies mainly in the bc plane, and (3) van der Waals interactions involving aliphatic residues.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.


Financial support by NSERC, FQRNT, QC, Canada, and “Programme de collaboration universités-collèges” as well as RQCHP (Réseau Québécois de Calcul de Haute Performance) is gratefully acknowledged for computational resources.

Supplementary Materials

Supplementary Material: Crystallographic Information File (CIF) for the proline derivative 1.

  1. Supplementary Material


  1. K. Biradha, C. Su, and J. J. Vittal, “Recent developments in crystal engineering,” Crystal Growth and Design, vol. 11, no. 4, pp. 875–886, 2011. View at: Publisher Site | Google Scholar
  2. G. R. Desiraju, “Crystal engineering: from molecule to crystal,” Journal of the American Chemical Society, vol. 135, no. 27, pp. 9952–9967, 2013. View at: Publisher Site | Google Scholar
  3. D. Gauthier, P. Baillargeon, M. Drouin, and Y. L. Dory, “Self-Assembly of cyclic peptides into nanotubes and then into highly anisotropic crystalline materials,” Angewandte Chemie International Edition, vol. 40, no. 24, pp. 4635–4638, 2001. View at: Google Scholar
  4. D. Pasini and M. Ricci, “Macrocycles as precursors for organic nanotubes,” Current Organic Synthesis, vol. 4, no. 1, pp. 59–80, 2007. View at: Publisher Site | Google Scholar
  5. P. Baillargeon, S. Bernard, D. Gauthier, R. Skouta, and Y. L. Dory, “Efficient synthesis and astonishing supramolecular architectures of several symmetric macrolactams,” Chemistry A, vol. 13, no. 33, pp. 9223–9235, 2007. View at: Publisher Site | Google Scholar
  6. P. Baillargeon and Y. L. Dory, “Supramolecular walls from cyclic peptides: modulating nature and strength of weak interactions,” Crystal Growth and Design, vol. 9, no. 8, pp. 3638–3645, 2009. View at: Publisher Site | Google Scholar
  7. T. Steiner, “The hydrogen bond in the solid state,” Angewandte Chemie International Edition, vol. 41, no. 1, pp. 48–76, 2002. View at: Google Scholar
  8. T. Steiner and G. R. Desiraju, “Distinction between the weak hydrogen bond and the van der Waals interaction,” Chemical Communications, no. 8, pp. 891–892, 1998. View at: Google Scholar
  9. G. R. Desiraju, “Strength and linearity of C–H···O bonds in molecular crystals: a database study of some terminal alkynes,” Journal of the Chemical Society, Chemical Communications, pp. 454–455, 1990. View at: Publisher Site | Google Scholar
  10. C. H. Schwalbe, “June Sutor and the C–H···O hydrogen bonding controversy,” Crystallography Reviews, vol. 18, no. 3, pp. 191–206, 2012. View at: Publisher Site | Google Scholar
  11. J. Bernstein, “It isn’t,” Crystal Growth & Design, vol. 13, no. 3, pp. 961–964, 2013. View at: Google Scholar
  12. G. R. Desiraju, “The C–H···O hydrogen bond in crystals: what is it?” Accounts of Chemical Research, vol. 24, no. 10, pp. 290–296, 1991. View at: Google Scholar
  13. G. R. Desiraju, “Hydrogen bridges in crystal engineering:  interactions without borders,” Accounts of Chemical Research, vol. 35, no. 7, pp. 565–573, 2002. View at: Publisher Site | Google Scholar
  14. G. R. Desiraju, “C–H···O and other weak hydrogen bonds. From crystal engineering to virtual screening,” Chemical Communications, no. 24, pp. 2995–3001, 2005. View at: Publisher Site | Google Scholar
  15. C. R. Jones, P. K. Baruah, A. L. Thompson, S. Scheiner, and M. D. Smith, “Can a C–H···O interaction be a determinant of conformation?” Journal of the American Chemical Society, vol. 134, no. 29, pp. 12064–12071, 2012. View at: Publisher Site | Google Scholar

Copyright © 2014 Pierre Baillargeon et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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