Buy article online - an online subscription or single-article purchase is required to access this article.
Download citation
Download citation
link to html
The title compound [systematic name: 8-chloro-11-(piperidin-4-yl­idene)-6,11-dihydro-5H-benzo[4,5]cyclo­hepta­[2,1-b]pyridine], C19H19ClN2, was crystallized from ethyl acetate. The inter­esting feature of the reported structure is that it does not contain any strong hydrogen bonds, although the mol­ecule contains a secondary NH group, which is a good hydrogen-bond donor.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270106012571/sk3005sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270106012571/sk3005Isup2.hkl
Contains datablock I

CCDC reference: 612468

Comment top

Desloratadine, (I), is a tricyclic antihistamine and is used to treat allergies. It is sold under brand names such as Clarinex and Aerius. It has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system. Desloratadine is an active metabolite of loratadine, which is also on the market. It is 10–20 times more potent as an antihistamine than loratadine. The solid-state chemistry of active pharmaceutical ingredients (API) is of both academic and applied interest and is concerned with the identification and characterization of different solid forms of APIs and their use in formulations.

Commercially available desloratadine, (I), was crystallized from EtOAc and crystals suitable for X-ray studies were obtained. The crystal structure was determined and the results are presented here. The molecular geometry and atom numbering are given in Fig. 1, and the packing arrangement is shown in Fig. 2. The only hydrogen bond present in the structure is a C—H···N interaction between the phenyl atom H11 and the pyridine atom N1. This interaction gives rise to an infinite zigzag chain, with piperidine rings alternating and pointing outwards on either side of the chain. Two such adjacent chains pack by placing their piperidine fragments into the space between two fragments of the adjacent chain and vice-versa, as shown in Fig. 2. This is basically a close-packed arrangement.

The most interesting feature of the crystal structure of (I) is that the piperidine N—H group is not hydrogen bonded in a conventional sense (N—H···N), although there are two N-atom acceptors in the molecule. A search of the Cambridge Structural Database (CSD, Version?; Allen, 2002) was carried out for entries which contain only N—H as a hydrogen-bond donor and where this N—H is not hydrogen bonded to any acceptor. The constraints used in this search were as follows: R < 0.05, no errors, not polymeric, no ions, only organics. 543 hits were obtained. However, analysis showed that, in almost all these cases, the N—H group is sterically hindered. It is therefore surprising that, in the case of desloratadine, which has a sterically unhindered N—H group, no hydrogen bonds are formed. The reason for this may lie in the awkward shape of the molecule. This reasoning was supported with a computational study using Polymorph Predictor (Accelrys, Year?). The polymorph prediction was carried out with the DREIDING2.21 force-field in five space groups, P21, C2/c, P1, P21/c and P212121. Except in C2/c, the most stable structure predicted was very similar to the experimental structure, in that no N—H···N hydrogen bond is present. Crystal structure prediction in the experimental space group (P21) gave the most stable structure, which was identical to the experimental structure. This is a good validation of the force field.

Desiraju (2002) has discussed a similar issue in his article entitled `Bond free' with respect to the literature example of the oxalic acid–phthalocyanine complex (Liu et al., 2002) and also alloxan (Coombes et al., 1997; Beyer et al., 2001). He concluded that crystal structures are determined by an interplay of both space filling and hydrogen bonding, such that the free energy is a minimum, and that the very occasional appearance of a crystal structure where sterically unhindered X—H groups do not form strong X—H···A interactions is a statistical issue, brought about by the fact that a very large number of crystal structures of small organic molecules are being determined today.

To date, two polymorphs of desloratadine have been reported in a patent application (Toth et al., 2004) but no crystal structure data are available. A comparison of the powder X-ray spectrum given in the patent and that simulated from the single-crystal data of the present study showed that the single-crystal obtained by us corresponds to form 1 of desloratadine. We feel it is possible to realise experimentally the hydrogen-bonded structure obtained computationally in the C2/c space group because it is only 2 kcal mol−1 molecule−1 (1 kcal mol−1 = 4.184 kJ mol−1) less stable than the experimental P21 structure reported here.

Experimental top

Desloratadine (100 mg) was dissolved in EtOAc (10 ml). The solution was filtered and the filtrate was allowed to crystallize by slow evaporation over a period of 2 d. Plate-like crystals of (I) were obtained from the solution and used for single-crystal X-ray diffraction studies.

Refinement top

Atoms H1 and H11 of the N—H and C—H groups, respectively, were located in difference Fourier maps and refined isotropically. All other H atoms were generated with idealized geometry and included in the refinement using a riding model, with C—H = 0.93 Å and Uiso(H) = 1.2Ueq(C) for aromatic H atoms, and C—H = 0.97 Å and Uiso(H) = 1.2Ueq(C) for methylene H atoms. The Flack parameter (Flack, 1983) was determined using a BASF/TWIN type of refinement. 1106 Friedel pairs were used for the analysis.

Computing details top

Data collection: SMART (Bruker, 1999); cell refinement: SMART; data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. A view of the molecular structure of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 2] Fig. 2. A stereoview of the packing arrangement, showing two close-packed desloratadine zigzag chains.
8-chloro-11-(4-piperidinylidene)-6,11-dihydro-5H- benzo[4,5]cyclohepta[2,1-b]pyridine top
Crystal data top
C19H19ClN2F(000) = 328
Mr = 310.81Dx = 1.373 Mg m3
Monoclinic, P21Melting point: 158 K
Hall symbol: P 2ybMo Kα radiation, λ = 0.71073 Å
a = 6.9336 (12) ÅCell parameters from 2389 reflections
b = 11.998 (2) Åθ = 2.3–25.9°
c = 9.4691 (16) ŵ = 0.25 mm1
β = 107.365 (2)°T = 100 K
V = 751.8 (2) Å3Plate, colourless
Z = 20.47 × 0.24 × 0.11 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
2550 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.023
Graphite monochromatorθmax = 26.0°, θmin = 2.3°
ϕ and ω scansh = 88
4424 measured reflectionsk = 1314
2661 independent reflectionsl = 811
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.032H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.075 w = 1/[σ2(Fo2) + (0.035P)2 + 0.1332P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2661 reflectionsΔρmax = 0.21 e Å3
208 parametersΔρmin = 0.21 e Å3
1 restraintAbsolute structure: Flack (1983), with 1106 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.04 (5)
Crystal data top
C19H19ClN2V = 751.8 (2) Å3
Mr = 310.81Z = 2
Monoclinic, P21Mo Kα radiation
a = 6.9336 (12) ŵ = 0.25 mm1
b = 11.998 (2) ÅT = 100 K
c = 9.4691 (16) Å0.47 × 0.24 × 0.11 mm
β = 107.365 (2)°
Data collection top
Bruker SMART CCD area-detector
diffractometer
2550 reflections with I > 2σ(I)
4424 measured reflectionsRint = 0.023
2661 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.032H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.075Δρmax = 0.21 e Å3
S = 1.05Δρmin = 0.21 e Å3
2661 reflectionsAbsolute structure: Flack (1983), with 1106 Friedel pairs
208 parametersAbsolute structure parameter: 0.04 (5)
1 restraint
Special details top

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

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl11.30938 (7)0.26310 (4)0.25228 (5)0.02176 (14)
N11.0382 (3)0.35354 (15)0.23443 (18)0.0183 (4)
N20.3026 (3)0.21123 (17)0.0094 (2)0.0217 (5)
C11.0218 (3)0.27342 (18)0.3292 (2)0.0151 (4)
C21.1542 (3)0.44150 (19)0.2915 (2)0.0206 (5)
C31.2556 (3)0.45345 (19)0.4397 (2)0.0209 (5)
C41.2392 (3)0.37022 (18)0.5353 (2)0.0176 (5)
C51.1214 (3)0.27722 (18)0.4815 (2)0.0162 (4)
C61.0939 (3)0.18222 (18)0.5774 (2)0.0178 (4)
C71.2008 (3)0.07625 (19)0.5542 (2)0.0169 (4)
C81.1423 (3)0.02314 (18)0.4010 (2)0.0143 (4)
C91.2325 (3)0.07951 (18)0.3917 (2)0.0151 (4)
C101.1965 (3)0.13316 (19)0.2576 (2)0.0171 (5)
C111.0735 (3)0.08755 (19)0.1277 (2)0.0170 (4)
C120.9822 (3)0.01259 (19)0.1379 (2)0.0167 (4)
C131.0077 (3)0.06879 (18)0.2721 (2)0.0140 (4)
C140.8931 (3)0.17469 (18)0.2692 (2)0.0146 (4)
C150.6896 (3)0.17988 (18)0.2193 (2)0.0154 (4)
C160.5509 (3)0.0826 (2)0.1640 (2)0.0184 (4)
C170.4130 (3)0.10602 (19)0.0057 (2)0.0194 (5)
C180.4355 (3)0.3050 (2)0.0511 (2)0.0214 (5)
C190.5733 (3)0.28702 (19)0.2100 (2)0.0187 (5)
H10.214 (3)0.206 (2)0.034 (2)0.018 (6)*
H21.16730.49900.22600.025*
H31.33520.51780.47510.025*
H41.30840.37640.63800.021*
H6A0.94770.16660.55590.021*
H6B1.14640.20480.68250.021*
H7A1.18020.01970.62440.020*
H7B1.34740.09240.58270.020*
H91.31950.11270.47850.018*
H111.054 (3)0.1273 (19)0.039 (2)0.015 (6)*
H120.89770.04530.04970.020*
H16A0.46700.06970.23070.022*
H16B0.63180.01460.16400.022*
H17A0.49680.10670.06260.023*
H17B0.31450.04430.02500.023*
H18A0.35150.37200.04940.026*
H18B0.52110.31980.01380.026*
H19A0.66860.35020.23960.022*
H19B0.49040.28400.27890.022*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0233 (2)0.0149 (3)0.0290 (3)0.0025 (2)0.0108 (2)0.0017 (2)
N10.0201 (8)0.0158 (10)0.0183 (8)0.0005 (8)0.0047 (7)0.0004 (8)
N20.0170 (8)0.0229 (13)0.0233 (9)0.0007 (8)0.0033 (7)0.0006 (8)
C80.0132 (9)0.0145 (11)0.0162 (10)0.0022 (9)0.0062 (8)0.0003 (8)
C90.0127 (9)0.0151 (12)0.0171 (10)0.0004 (9)0.0040 (7)0.0033 (8)
C100.0133 (9)0.0113 (12)0.0293 (11)0.0021 (9)0.0103 (8)0.0005 (9)
C140.0203 (10)0.0127 (12)0.0111 (9)0.0005 (9)0.0049 (8)0.0005 (8)
C180.0175 (10)0.0218 (14)0.0231 (11)0.0045 (10)0.0034 (9)0.0034 (9)
C50.0120 (9)0.0172 (12)0.0195 (10)0.0038 (9)0.0051 (8)0.0024 (9)
C40.0140 (9)0.0163 (12)0.0211 (10)0.0048 (9)0.0028 (8)0.0056 (9)
C10.0114 (9)0.0162 (11)0.0172 (9)0.0033 (8)0.0038 (7)0.0018 (8)
C130.0126 (9)0.0136 (11)0.0163 (9)0.0036 (9)0.0050 (7)0.0002 (8)
C150.0180 (10)0.0153 (12)0.0120 (9)0.0005 (9)0.0029 (8)0.0010 (8)
C70.0177 (9)0.0168 (12)0.0155 (9)0.0018 (9)0.0039 (8)0.0021 (8)
C110.0165 (10)0.0155 (12)0.0180 (10)0.0042 (9)0.0037 (8)0.0029 (9)
C60.0182 (10)0.0188 (12)0.0165 (10)0.0014 (9)0.0057 (8)0.0013 (8)
C20.0195 (10)0.0178 (12)0.0264 (11)0.0003 (10)0.0097 (9)0.0021 (9)
C170.0171 (10)0.0216 (13)0.0171 (10)0.0008 (10)0.0017 (8)0.0003 (9)
C120.0133 (10)0.0173 (12)0.0173 (10)0.0027 (9)0.0012 (8)0.0013 (8)
C30.0162 (10)0.0152 (13)0.0314 (12)0.0003 (10)0.0071 (9)0.0053 (9)
C190.0153 (10)0.0187 (12)0.0212 (10)0.0001 (9)0.0042 (8)0.0017 (9)
C160.0165 (9)0.0186 (12)0.0203 (10)0.0016 (9)0.0059 (8)0.0006 (9)
Geometric parameters (Å, º) top
Cl1—C101.752 (2)C4—H40.9500
C14—C151.349 (3)C13—C121.403 (3)
C14—C11.490 (3)C15—C161.503 (3)
C14—C131.494 (3)C15—C191.506 (3)
N2—C181.458 (3)C7—C61.521 (3)
N2—C171.461 (3)C7—H7A0.9900
N2—H10.84 (2)C7—H7B0.9900
C10—C91.378 (3)C11—C121.375 (3)
C10—C111.384 (3)C11—H110.94 (2)
C9—C81.396 (3)C6—H6A0.99
C9—H90.9500C6—H6B0.99
C8—C131.407 (3)C2—C31.376 (3)
C8—C71.524 (3)C2—H20.95
N1—C21.339 (3)C17—C161.545 (3)
N1—C11.343 (3)C17—H17A0.99
C18—C191.538 (3)C17—H17B0.99
C18—H18A0.9900C12—H120.95
C18—H18B0.9900C3—H30.9500
C5—C41.387 (3)C19—H19A0.99
C5—C11.401 (3)C19—H19B0.99
C5—C61.505 (3)C16—H16A0.99
C4—C31.375 (3)C16—H16B0.99
C15—C14—C1122.80 (18)C6—C7—H7B107.6
C15—C14—C13122.69 (18)C8—C7—H7B107.6
C1—C14—C13114.49 (16)H7A—C7—H7B107.0
C18—N2—C17112.13 (16)C12—C11—C10117.23 (19)
C18—N2—H1109.8 (16)C12—C11—H11124.2 (13)
C17—N2—H1109.0 (17)C10—C11—H11118.6 (13)
C9—C10—C11121.9 (2)C5—C6—C7112.99 (16)
C9—C10—Cl1118.84 (16)C5—C6—H6A109.0
C11—C10—Cl1119.25 (17)C7—C6—H6A109.0
C10—C9—C8120.57 (18)C5—C6—H6B109.0
C10—C9—H9119.7C7—C6—H6B109.0
C8—C9—H9119.7H6A—C6—H6B107.8
C9—C8—C13118.86 (18)N1—C2—C3123.8 (2)
C9—C8—C7115.59 (17)N1—C2—H2118.1
C13—C8—C7125.55 (18)C3—C2—H2118.1
C2—N1—C1117.04 (17)N2—C17—C16113.96 (17)
N2—C18—C19114.31 (18)N2—C17—H17A108.8
N2—C18—H18A108.7C16—C17—H17A108.8
C19—C18—H18A108.7N2—C17—H17B108.8
N2—C18—H18B108.7C16—C17—H17B108.8
C19—C18—H18B108.7H17A—C17—H17B107.7
H18A—C18—H18B107.6C11—C12—C13123.22 (19)
C4—C5—C1117.4 (2)C11—C12—H12118.4
C4—C5—C6123.66 (18)C13—C12—H12118.4
C1—C5—C6118.96 (18)C4—C3—C2118.6 (2)
C3—C4—C5119.84 (19)C4—C3—H3120.7
C3—C4—H4120.1C2—C3—H3120.7
C5—C4—H4120.1C15—C19—C18109.99 (17)
N1—C1—C5123.38 (19)C15—C19—H19A109.7
N1—C1—C14118.35 (17)C18—C19—H19A109.7
C5—C1—C14118.26 (18)C15—C19—H19B109.7
C12—C13—C8118.04 (19)C18—C19—H19B109.7
C12—C13—C14118.01 (17)H19A—C19—H19B108.2
C8—C13—C14123.95 (17)C15—C16—C17110.08 (17)
C14—C15—C16125.43 (19)C15—C16—H16A109.6
C14—C15—C19123.06 (19)C17—C16—H16A109.6
C16—C15—C19111.50 (16)C15—C16—H16B109.6
C6—C7—C8118.99 (16)C17—C16—H16B109.6
C6—C7—H7A107.6H16A—C16—H16B108.2
C8—C7—H7A107.6
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C11—H11···N1i0.940 (18)2.485 (18)3.357 (3)154.4 (18)
Symmetry code: (i) x+2, y1/2, z.

Experimental details

Crystal data
Chemical formulaC19H19ClN2
Mr310.81
Crystal system, space groupMonoclinic, P21
Temperature (K)100
a, b, c (Å)6.9336 (12), 11.998 (2), 9.4691 (16)
β (°) 107.365 (2)
V3)751.8 (2)
Z2
Radiation typeMo Kα
µ (mm1)0.25
Crystal size (mm)0.47 × 0.24 × 0.11
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
4424, 2661, 2550
Rint0.023
(sin θ/λ)max1)0.618
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.032, 0.075, 1.05
No. of reflections2661
No. of parameters208
No. of restraints1
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.21, 0.21
Absolute structureFlack (1983), with 1106 Friedel pairs
Absolute structure parameter0.04 (5)

Computer programs: SMART (Bruker, 1999), SMART, SAINT (Bruker, 1999), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997), SHELXTL.

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C11—H11···N1i0.940 (18)2.485 (18)3.357 (3)154.4 (18)
Symmetry code: (i) x+2, y1/2, z.
 

Subscribe to Acta Crystallographica Section C: Structural Chemistry

The full text of this article is available to subscribers to the journal.

If you have already registered and are using a computer listed in your registration details, please email support@iucr.org for assistance.

Buy online

You may purchase this article in PDF and/or HTML formats. For purchasers in the European Community who do not have a VAT number, VAT will be added at the local rate. Payments to the IUCr are handled by WorldPay, who will accept payment by credit card in several currencies. To purchase the article, please complete the form below (fields marked * are required), and then click on `Continue'.
E-mail address* 
Repeat e-mail address* 
(for error checking) 

Format*   PDF (US $40)
   HTML (US $40)
   PDF+HTML (US $50)
In order for VAT to be shown for your country javascript needs to be enabled.

VAT number 
(non-UK EC countries only) 
Country* 
 

Terms and conditions of use
Contact us

Follow Acta Cryst. C
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds