research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

Crystal structure of pirfenidone (5-methyl-1-phenyl-1H-pyridin-2-one): an active pharmaceutical ingredient (API)

aDipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Largo Donegani 2/3, I-28100, Novara, Italy, bR&D Division, PROCOS S.p.A., Via G. Matteotti 249, 28062 Cameri (Novara), Italy, and cDipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, I-20133 Milano, Italy
*Correspondence e-mail: valentina.colombo@unimi.it

Edited by B. Therrien, University of Neuchâtel, Switzerland (Received 4 April 2019; accepted 6 May 2019; online 11 June 2019)

The crystal structure of pirfenidone, C12H11NO [alternative name: 5-methyl-1-phenyl­pyridin-2(1H)-one], an active pharmaceutical ingredient (API) approved in Europe and Japan for the treatment of Idiopathic pulmonary fibrosis (IPF), is reported here for the first time. It was crystallized from toluene by the temperature gradient technique, and crystallizes in the chiral monoclinic space group P21. The phenyl and pyridone rings are inclined to each other by 50.30 (11)°. In the crystal, mol­ecules are linked by C–H⋯O hydrogen bonds involving the same acceptor atom, forming undulating layers lying parallel to the ab plane.

1. Chemical context

Idiopathic Pulmonary Fibrosis (IPF) is a lung disease characterized by cough, scars and dyspnea that leads to progressive and irreversible loss of lung function. Pirfenidone (systematic name: 5-methyl-1-phenyl-1H-pyridin-2-one) has been approved in Japan since 2008 (Pirespa®) and in Europe since 2011 (Esbriet®) for the treatment of IPF, even if its mechanism of action has not been completely elucidated (Richeldi et al., 2011[Richeldi, L., Yasothan, U. & Kirkpatrick, P. (2011). Nat. Rev. Drug Discov. 10, 489-490.]). Different synthetic approaches have been reported, mainly relying on N-aryl­ation reactions of 5-methyl-2-pyridone (Liu et al., 2009[Liu, K. K.-C., Sakya, S. M., O'Donnell, C. J. & Li, J. (2009). Mini Rev. Med. Chem. 9, 1655-1675.]; Crifar et al., 2014[Crifar, C., Petiot, P., Ahmad, T. & Gagnon, A. (2014). Chem. Eur. J. 20, 2755-2760.]; Jung et al., 2016[Jung, S.-H., Sung, D.-B., Park, C.-H. & Kim, W.-S. (2016). J. Org. Chem. 81, 7717-7724.]; Falb et al., 2017[Falb, E., Ulanenko, K., Tor, A., Gottesfeld, R., Weitman, M., Afri, M., Gottlieb, H. & Hassner, A. (2017). Green Chem. 19, 5046-5053.]). Pirfenidone has been known since 1974 (Gadekar, 1974[Gadekar, S. M. (1974). Patent DE 2362958.]) and its anti­fibrotic properties were described in 1990 (Margolin, 1990[Margolin, S. B. C. O. T. (1990). Patent EP 0383591.]). Nevertheless, despite its formulation as oral tablets, no information on the solid-state structure of this compound has been reported to date. In the present study, we report and analyse the crystal structure of pirfenidone.

[Scheme 1]

2. Structural commentary

The mol­ecular structure of pirfenidone is shown in Fig. 1[link]. This axially chiral mol­ecule crystallizes in the monoclinic space group P21, with one mol­ecule in a general position. The mol­ecule is far from planar with the phenyl (C7–C12) and pyridinone (N1/C1–C5) rings subtending a dihedral angle of 50.30 (11)°.

[Figure 1]
Figure 1
A view of the mol­ecular structure of pirfenidone with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

3. Supra­molecular features

In the crystal, mol­ecules are linked by C—H⋯O hydrogen bonds involving the same acceptor atom (Table 1[link]), forming an undulating network, enclosing R43(20) ring motifs, and lying parallel to the ab plane (Figs. 2[link] and 3[link]). The R43(20) ring motifs are clearly visible in Fig. 3[link]. There are no other significant inter­molecular contacts present according to the analysis of the crystal structure using PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C8—H8⋯O1i 0.93 2.33 3.203 (3) 156
C10—H10⋯O1ii 0.93 2.46 3.310 (3) 152
Symmetry codes: (i) x-1, y, z; (ii) [-x+2, y-{\script{1\over 2}}, -z+2].
[Figure 2]
Figure 2
A view along the a axis of the crystal packing of pirfenidone. The C—H⋯O hydrogen bonds (see Table 1[link]) are shown as dashed lines.
[Figure 3]
Figure 3
A view along the c axis of the crystal packing of pirfenidone. The C—H⋯O hydrogen bonds (see Table 1[link]) are shown as dashed lines.

4. Database Survey

A search of the Cambridge Structural Database (CSD, Version 5.40, February 2019; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for 1-phenyl­pyridin-2(1H)-ones, excluding structures with ring atoms being included in further cyclic moieties, gave 40 hits (see supporting information file S1). Only six of these compounds involve an unsubstituted phenyl ring as in the title compound. When considering compounds with no substituent in position-6 of the pyridinone ring (on atom C5 in the title compound; Fig. 1[link]) only three structures fit this extra criteria, viz. S-ethyl 2-oxo-1-phenyl-1,2-di­hydro-3-pyridine­carbo­thio­ate (CSD refcode NOLBIA; Liu et al., 2008[Liu, J., Liang, D., Wang, M. & Liu, Q. (2008). Synthesis, pp. 3633-3638.]), monoclinic space group P21, 4-chloro-6-oxo-1-phenyl-1,6-di­hydro­pyridine-3-carbaldehyde (QIWFIM; Xiang et al., 2008[Xiang, D., Wang, K., Liang, Y., Zhou, G. & Dong, D. (2008). Org. Lett. 10, 345-348.]), monoclinic space group P21/c, and methyl 5-benzoyl-2-oxo-1-phenyl-1,2-di­hydro­pyridine-4-carboxyl­ate (TEMKIH; Shao et al., 2012[Shao, Y., Yao, W., Liu, J., Zhu, K. & Li, Y. (2012). Synthesis, 44, 3301-3306.]), ortho­rhom­bic space group Pna21 with two independent mol­ecules in the asymmetric unit. In these three compounds, the phenyl ring is inclined to the pyridone ring by ca 65.50, 64.66 and 55.83/57.12°, respectively. This dihedral angle in the title compound, pirfenidone, is 50.30 (11)°. In the other three compounds [AQIKIV (Gorobets et al., 2010[Gorobets, N. Yu., Tkachova, V. P., Tkachov, R. P., Dyachenko, O. D., Rusanov, E. B. & Dyachenko, V. D. (2010). ARKIVOC, 11, 254-264.]), BAFPUV (Dyachenko et al., 2011[Dyachenko, V. D., Butyukova, O. S., Dyachenko, A. D. & Shishkin, O. V. (2011). Zh. Obshch. Khim. 81, 857-868.]) and WEDCEP (Allais et al., 2012[Allais, C., Baslé, O., Grassot, J.-M., Fontaine, M., Anguille, S., Rodriguez, J. & Constantieux, T. (2012). Adv. Synth. Catal. 354, 2084-2088.]) – see supporting information file S1] with a substituent in position-6 of the pyridinone ring the corresponding dihedral angle varies from ca 73.02 to 89.28° as a result of steric hindrance.

5. Synthesis and crystallization

Pirfenidone was obtained in > 99.5% purity according to the method published previously (Mossotti et al., 2018[Mossotti, M., Barozza, A., Roletto, J. & Paissoni, P. (2018). Patent US 2018319747.]). Single crystals were grown in the following way: approximately 100 mg of pirfenidone in 2 mL of toluene was heated until complete dissolution. The flask with this solution was then closed and kept at 273–278 K. Well-formed colourless crystals of pirfenidone were obtained after 1 week. The melting point of this crystal form, determined by DSC analysis (heating rate 10 K min−1), is 383 K. This crystallization procedure must be performed in order to grow single crystals suitable for X-ray diffraction analysis and not with the aim of increasing the purity of the product. It is worth nothing that the industrial process is already optimized for the isolation of a pure API (> 99.5%) and a further crystallization step is not needed to improve its purity. We performed several other crystallization trials in order to search for other possible forms of pirfenidone; however, each crystallization attempt gave rise to the same crystal form.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The H atoms were included in calculated positions and treated as riding: C—H = 0.93–0.96 Å with Uiso(H) = 1.5Ueq(C-meth­yl) and 1.2Ueq(C) for other H atoms.

Table 2
Experimental details

Crystal data
Chemical formula C12H11NO
Mr 185.22
Crystal system, space group Monoclinic, P21
Temperature (K) 293
a, b, c (Å) 6.2525 (8), 7.797 (1), 10.2810 (13)
β (°) 104.744 (2)
V3) 484.70 (11)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.08
Crystal size (mm) 0.50 × 0.45 × 0.05
 
Data collection
Diffractometer Bruker SMART APEX CCD
Absorption correction Multi-scan (SADABS; Bruker, 2010[Bruker (2010). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.692, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections 4547, 2128, 1879
Rint 0.019
(sin θ/λ)max−1) 0.643
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.095, 1.04
No. of reflections 2128
No. of parameters 127
No. of restraints 1
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.11, −0.20
Absolute structure Flack x determined using 762 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 0.3 (4)
Computer programs: APEX2 and SAINT (Bruker, 2010[Bruker (2010). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT2017 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2017 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]), PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information


Computing details top

Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT (Bruker, 2010); program(s) used to solve structure: SHELXT2017 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2017 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2017 (Sheldrick, 2015b), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

5-Methyl-1-phenylpyridin-2(1H)-one top
Crystal data top
C12H11NODx = 1.269 Mg m3
Mr = 185.22Melting point: 375 K
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 6.2525 (8) ÅCell parameters from 2547 reflections
b = 7.797 (1) Åθ = 3.3–27.2°
c = 10.2810 (13) ŵ = 0.08 mm1
β = 104.744 (2)°T = 293 K
V = 484.70 (11) Å3Plate, colourless
Z = 20.50 × 0.45 × 0.05 mm
F(000) = 196
Data collection top
Bruker SMART APEX CCD
diffractometer
1879 reflections with I > 2σ(I)
ω scansRint = 0.019
Absorption correction: multi-scan
(SADABS; Bruker, 2010)
θmax = 27.2°, θmin = 2.1°
Tmin = 0.692, Tmax = 0.746h = 88
4547 measured reflectionsk = 910
2128 independent reflectionsl = 1313
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.037 w = 1/[σ2(Fo2) + (0.0528P)2 + 0.0476P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.095(Δ/σ)max < 0.001
S = 1.04Δρmax = 0.11 e Å3
2128 reflectionsΔρmin = 0.20 e Å3
127 parametersAbsolute structure: Flack x determined using 762 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraintAbsolute structure parameter: 0.3 (4)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. none

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.7599 (2)0.5275 (2)0.62509 (16)0.0382 (4)
O11.0951 (2)0.6634 (3)0.69330 (17)0.0602 (5)
C10.9386 (3)0.6188 (3)0.6002 (2)0.0437 (5)
C50.5769 (3)0.4849 (3)0.5233 (2)0.0395 (5)
H50.4604210.4280460.5456470.047*
C70.7635 (3)0.4782 (3)0.76141 (19)0.0401 (5)
C40.5595 (3)0.5219 (3)0.3929 (2)0.0430 (5)
C120.9445 (4)0.3913 (3)0.8390 (2)0.0497 (5)
H121.0666160.3687120.8056870.060*
C80.5830 (3)0.5134 (3)0.8108 (2)0.0481 (5)
H80.4621140.5720840.7582310.058*
C60.3599 (4)0.4732 (3)0.2835 (2)0.0579 (6)
H6A0.4001280.3872660.2271270.087*
H6B0.3043460.5725650.2304470.087*
H6C0.2476950.4286520.3228170.087*
C110.9409 (5)0.3383 (3)0.9672 (2)0.0616 (7)
H111.0610570.2788171.0197370.074*
C30.7416 (4)0.6079 (3)0.3637 (2)0.0527 (6)
H30.7377080.6330550.2747010.063*
C20.9189 (4)0.6537 (3)0.4608 (2)0.0540 (6)
H21.0339790.7106170.4368930.065*
C90.5836 (4)0.4604 (4)0.9395 (2)0.0623 (7)
H90.4625010.4842540.9735530.075*
C100.7616 (5)0.3728 (4)1.0174 (2)0.0649 (7)
H100.7606340.3371711.1035770.078*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0355 (8)0.0426 (9)0.0362 (8)0.0009 (8)0.0084 (7)0.0007 (7)
O10.0399 (8)0.0725 (11)0.0631 (11)0.0111 (8)0.0038 (7)0.0046 (9)
C10.0368 (10)0.0430 (12)0.0524 (12)0.0007 (9)0.0134 (9)0.0023 (10)
C50.0380 (9)0.0395 (11)0.0398 (10)0.0026 (9)0.0078 (8)0.0011 (9)
C70.0411 (10)0.0397 (11)0.0362 (10)0.0013 (8)0.0034 (8)0.0002 (8)
C40.0524 (11)0.0376 (11)0.0376 (10)0.0009 (10)0.0087 (9)0.0001 (9)
C120.0496 (12)0.0478 (12)0.0459 (12)0.0081 (10)0.0017 (10)0.0051 (10)
C80.0395 (10)0.0602 (13)0.0435 (11)0.0003 (10)0.0082 (8)0.0070 (11)
C60.0705 (15)0.0570 (15)0.0399 (11)0.0077 (13)0.0026 (11)0.0004 (11)
C110.0708 (16)0.0522 (14)0.0469 (13)0.0053 (12)0.0126 (12)0.0046 (11)
C30.0694 (15)0.0522 (14)0.0410 (11)0.0091 (11)0.0224 (11)0.0002 (10)
C20.0559 (13)0.0556 (14)0.0576 (14)0.0113 (12)0.0276 (11)0.0015 (11)
C90.0595 (14)0.0851 (19)0.0450 (13)0.0110 (13)0.0183 (11)0.0036 (13)
C100.0826 (19)0.0688 (17)0.0378 (12)0.0134 (16)0.0054 (12)0.0103 (12)
Geometric parameters (Å, º) top
N1—C51.381 (2)C8—C91.386 (3)
N1—C11.402 (2)C8—H80.9300
N1—C71.448 (3)C6—H6A0.9600
O1—C11.232 (3)C6—H6B0.9600
C1—C21.432 (3)C6—H6C0.9600
C5—C41.349 (3)C11—C101.375 (4)
C5—H50.9300C11—H110.9300
C7—C81.378 (3)C3—C21.338 (3)
C7—C121.384 (3)C3—H30.9300
C4—C31.417 (3)C2—H20.9300
C4—C61.501 (3)C9—C101.376 (4)
C12—C111.386 (4)C9—H90.9300
C12—H120.9300C10—H100.9300
C5—N1—C1121.93 (17)C4—C6—H6A109.5
C5—N1—C7118.39 (16)C4—C6—H6B109.5
C1—N1—C7119.67 (16)H6A—C6—H6B109.5
O1—C1—N1120.88 (19)C4—C6—H6C109.5
O1—C1—C2124.9 (2)H6A—C6—H6C109.5
N1—C1—C2114.20 (18)H6B—C6—H6C109.5
C4—C5—N1122.94 (19)C10—C11—C12120.7 (2)
C4—C5—H5118.5C10—C11—H11119.7
N1—C5—H5118.5C12—C11—H11119.7
C8—C7—C12120.74 (19)C2—C3—C4121.7 (2)
C8—C7—N1119.42 (17)C2—C3—H3119.1
C12—C7—N1119.81 (19)C4—C3—H3119.1
C5—C4—C3116.47 (19)C3—C2—C1122.6 (2)
C5—C4—C6122.2 (2)C3—C2—H2118.7
C3—C4—C6121.4 (2)C1—C2—H2118.7
C7—C12—C11119.0 (2)C10—C9—C8120.6 (2)
C7—C12—H12120.5C10—C9—H9119.7
C11—C12—H12120.5C8—C9—H9119.7
C7—C8—C9119.3 (2)C11—C10—C9119.7 (2)
C7—C8—H8120.4C11—C10—H10120.2
C9—C8—H8120.4C9—C10—H10120.2
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C8—H8···O1i0.932.333.203 (3)156
C10—H10···O1ii0.932.463.310 (3)152
Symmetry codes: (i) x1, y, z; (ii) x+2, y1/2, z+2.
 

Acknowledgements

VC gratefully acknowledges Professor H. Stoeckli-Evans for her helpful and valuable suggestions.

Funding information

Funding for this research was provided by: Università degli Studi di Milano (grant No. PSR2018_DIP_005_COLOMBO_VALENTINA to Valentina Colombo).

References

First citationAllais, C., Baslé, O., Grassot, J.-M., Fontaine, M., Anguille, S., Rodriguez, J. & Constantieux, T. (2012). Adv. Synth. Catal. 354, 2084–2088.  Web of Science CSD CrossRef CAS Google Scholar
First citationBruker (2010). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationCrifar, C., Petiot, P., Ahmad, T. & Gagnon, A. (2014). Chem. Eur. J. 20, 2755–2760.  Web of Science CrossRef CAS PubMed Google Scholar
First citationDyachenko, V. D., Butyukova, O. S., Dyachenko, A. D. & Shishkin, O. V. (2011). Zh. Obshch. Khim. 81, 857–868.  Google Scholar
First citationFalb, E., Ulanenko, K., Tor, A., Gottesfeld, R., Weitman, M., Afri, M., Gottlieb, H. & Hassner, A. (2017). Green Chem. 19, 5046–5053.  Web of Science CrossRef CAS Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationGadekar, S. M. (1974). Patent DE 2362958.  Google Scholar
First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CrossRef IUCr Journals Google Scholar
First citationJung, S.-H., Sung, D.-B., Park, C.-H. & Kim, W.-S. (2016). J. Org. Chem. 81, 7717–7724.  Web of Science CrossRef CAS PubMed Google Scholar
First citationLiu, J., Liang, D., Wang, M. & Liu, Q. (2008). Synthesis, pp. 3633–3638.  Web of Science CSD CrossRef Google Scholar
First citationLiu, K. K.-C., Sakya, S. M., O'Donnell, C. J. & Li, J. (2009). Mini Rev. Med. Chem. 9, 1655–1675.  Web of Science CrossRef CAS PubMed Google Scholar
First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationMargolin, S. B. C. O. T. (1990). Patent EP 0383591.  Google Scholar
First citationMossotti, M., Barozza, A., Roletto, J. & Paissoni, P. (2018). Patent US 2018319747.  Google Scholar
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationRicheldi, L., Yasothan, U. & Kirkpatrick, P. (2011). Nat. Rev. Drug Discov. 10, 489–490.  Web of Science CrossRef CAS PubMed Google Scholar
First citationShao, Y., Yao, W., Liu, J., Zhu, K. & Li, Y. (2012). Synthesis, 44, 3301–3306.  Web of Science CrossRef CAS Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationGorobets, N. Yu., Tkachova, V. P., Tkachov, R. P., Dyachenko, O. D., Rusanov, E. B. & Dyachenko, V. D. (2010). ARKIVOC, 11, 254–264.  Google Scholar
First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationXiang, D., Wang, K., Liang, Y., Zhou, G. & Dong, D. (2008). Org. Lett. 10, 345–348.  Web of Science CSD CrossRef PubMed CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds