N-Methyl-N-styrylcinnamamide (lansamide) from Clausena lansium in Vietnam

Luger, P.; Weber, M.; Thang, T.D.; Van Luu, H.; Dung, N.X.

doi:10.1107/S1600536809009611

organic compounds

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ISSN: 2056-9890

Volume 65| Part 4| April 2009| Page o809

doi:10.1107/S1600536809009611

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N-Methyl-N-styrylcinnamamide (lansamide) from Clausena lansium in Vietnam

Peter Luger,^a ^* Manuela Weber,^a Tran Dinh Thang,^b Hoang Van Luu ^b and Nguyen Xuan Dung ^c

^aInstitut für Chemie und Biochemie-Kristallographie, Fachbereich Biologie-Chemie-Pharmazie der Freien Universität, Fabeckstrasse 36a, 14195 Berlin, Germany, ^bFaculty of Chemistry, Vinh University, 182-Le Duan, Vinh City, Nghean Province, Vietnam, and ^cFaculty of Chemistry, College of Natural Sciences, Hanoi National University, 19-Le Thanh Tong Street, 10 000 Hanoi, Vietnam
^*Correspondence e-mail: luger@chemie.fu-berlin.de

(Received 13 March 2009; accepted 16 March 2009; online 19 March 2009)

The title compound, C₁₈H₁₇NO, was isolated from the seeds of Clausena lansium (wampee) (Rutaceae). The X-ray crystal structure analysis confirmed its chemical identity and revealed that it is solvent-free, in contrast to the previously reported monohydrate [Huang, Ou & Tang (2006 ). Acta Cryst. E62, o1987–o1988]. The molecular structures are practically identical but the molecules pack differently. In contrast to the monohydrate in which the water molecule generates two hydrogen bonds, no such intermolecular contacts are present in the title compound. The dihedral angle between the cinnamamide and the styryl group is 53.1 (1)°.

Related literature

For the structure of the monohydrate, see: Huang et al. (2006). For medicinal applications, see: Loi (2001 ).

Experimental

Crystal data

C₁₈H₁₇NO
M_r = 263.33
Triclinic, $[P \overline 1]$
a = 6.356 (1) Å
b = 9.265 (2) Å
c = 13.073 (3) Å
α = 80.45 (3)°
β = 77.22 (3)°
γ = 78.13 (3)°
V = 728.9 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 298 K
0.60 × 0.60 × 0.55 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: none
25654 measured reflections
5327 independent reflections
3962 reflections with I > 2σ(I)
R_int = 0.023

Refinement

R[F² > 2σ(F²)] = 0.060
wR(F²) = 0.190
S = 1.02
5327 reflections
182 parameters
H-atom parameters constrained
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Data collection: SMART (Bruker, 2004 ); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ) and SCHAKAL99 (Keller & Pierrard, 1999 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809009611/tk2394sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809009611/tk2394Isup2.hkl

checkCIF report

Comment top

The title compound N-methyl-N-styrylcinnamamide [N-methyl-3-phenyl-N-(2-phenylethenyl)-2-propenamide] (I) was isolated from the seeds of Clausena lansium (wampee) (Rutaceae). The leaves have been used as a folk medicine for the treatment of coughs, asthma and gastrointestinal diseases. The fruit is used for digestive disorders and the seeds are used for gastro-intestinal diseases such as acute and chronic gastrointestinal, ulcers, etc. (Loi, 2001).

The X-ray structure of the monohydrate of (I) was reported recently (Huang et al., 2006) wherein it was reported that "the corresponding anhydrous compound is a pale-yellow liquid at room temperature". Surprisingly, we could grow pale-yellow crystals of the water-free form from n-hexane and its X-ray structure, which is subject of this study, was carried out to confirm its chemical identity.

The molecular structure of (I) is shown in Fig. 1 and its superposition with the molecule found in the monohydrate structure is shown in Fig. 2. Both structures are practically identical with a small difference of 10° in the rotation of the styryl phenyl ring along the bond C11—C12: torsion angle C10—C11—C12—C13= 148.7 (1)° for (I) and 139.0 (3)° for the monohydrate. Bond lengths and angles, which are all in the expected ranges, have an average difference of 0.007 Å and 0.4° between (I) and the monohydrate.

The triclinic lattice of (I) is illustrated in Fig. 3. In contrast to the monohydrate where the water molecule generates two hydrogen bonds in a body centered tetragonal lattice, no such intermolecular contacts are present in (I). Nevertheless, the packing in the triclinic lattice shows some characteristic features. The molecule consists of two planar fragments, the cinnamamide and the styryl group, forming an interplanar angle of 53.1 (1)°. In molecular pairs related by the inversion centre at (1/2, 1/2, 1), the cinnamamide fragments are aligned in parallel planes with a shortest contact distance of C atoms of adjacent planes being C1···C8 = 3.664 (3) Å. Such an arrangement of cinnamamide groups was also observed in the monohydrate structure. The styryl groups also form co-planar planes for molecules related by the inversion centre at (1/2, 1/2, 1/2), the shortest distance between C atoms of adjacent planes is C11···C17 = 3.730 (3) Å (see dashed lines in Fig. 3). This arrangement of styryl groups was not observed in the monohydrate structure.

Related literature top

For related literature, see: Huang et al. (2006); Loi (2001).

Experimental top

The dried seeds of C. lansium (3,0 kg) were powdered and extracted with MeOH at room temperature, and the combined extracts were concentrated under reduced pressure to give a deep-brown syrup (160 g). This was partitioned between H₂O and n-hexane. The n-hexane-soluble residue (85 g) was chromatographed over a silica gel column, which developed by gradient elution with n-hexane and increasing concentrations of Me₂CO to afford forty fractions. Fractions were combined on their TLC. After standing for several day, fractions 9–11 recrystallized from n-hexane to afford pale-yellow lansamide (2554 mg).

Computing details top

Data collection: SMART (Bruker, 2004); cell refinement: SAINT (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and SCHAKAL99 (Keller & Pierrard, 1999); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of (I) with atom numbering scheme, displacement ellipsoids are shown at the 50% probability level.
	Fig. 2. Superposition of (I) (red) and the monohydrate (blue) forms of lansamide.
	Fig. 3. Stereo drawing of packing in (I) shown in projection onto the yz-plane. The C1···C8 and C11···C17 contacts are shown by dashed lines.

N-Methyl-N-styrylcinnamamide top

Crystal data top

C₁₈H₁₇NO	Z = 2
M_r = 263.33	F(000) = 280
Triclinic, P1	D_x = 1.200 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.356 (1) Å	Cell parameters from 5327 reflections
b = 9.265 (2) Å	θ = 2.3–33.3°
c = 13.073 (3) Å	µ = 0.07 mm⁻¹
α = 80.45 (3)°	T = 298 K
β = 77.22 (3)°	Block, yellow
γ = 78.13 (3)°	0.60 × 0.60 × 0.55 mm
V = 728.9 (3) Å³

Data collection top

Bruker SMART CCD area-detector diffractometer	3962 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.023
Graphite monochromator	θ_max = 33.3°, θ_min = 2.3°
ω scans	h = −9→9
25654 measured reflections	k = −13→14
5327 independent reflections	l = 0→20

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.060	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.190	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.0892P)² + 0.1313P] where P = (F_o² + 2F_c²)/3
5327 reflections	(Δ/σ)_max < 0.001
182 parameters	Δρ_max = 0.36 e Å⁻³
0 restraints	Δρ_min = −0.14 e Å⁻³

Crystal data top

C₁₈H₁₇NO	γ = 78.13 (3)°
M_r = 263.33	V = 728.9 (3) Å³
Triclinic, P1	Z = 2
a = 6.356 (1) Å	Mo Kα radiation
b = 9.265 (2) Å	µ = 0.07 mm⁻¹
c = 13.073 (3) Å	T = 298 K
α = 80.45 (3)°	0.60 × 0.60 × 0.55 mm
β = 77.22 (3)°

Data collection top

Bruker SMART CCD area-detector diffractometer	3962 reflections with I > 2σ(I)
25654 measured reflections	R_int = 0.023
5327 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.060	0 restraints
wR(F²) = 0.190	H-atom parameters constrained
S = 1.02	Δρ_max = 0.36 e Å⁻³
5327 reflections	Δρ_min = −0.14 e Å⁻³
182 parameters

Special details top

Experimental. Bruker AXS APEX CCD area detector on Huber four circle diffractometer is used

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

	x	y	z	U_iso*/U_eq
C1	0.6509 (2)	0.21826 (15)	0.99509 (11)	0.0553 (3)
H1	0.5292	0.2328	0.9636	0.066*
C2	0.6807 (3)	0.10113 (17)	1.07380 (11)	0.0650 (4)
H2	0.5794	0.0373	1.0949	0.078*
C3	0.8605 (3)	0.07815 (17)	1.12150 (11)	0.0653 (4)
H3	0.8807	−0.0014	1.1742	0.078*
C4	1.0085 (3)	0.17266 (18)	1.09103 (12)	0.0671 (4)
H4	1.1283	0.1585	1.1238	0.080*
C5	0.9801 (2)	0.28959 (16)	1.01128 (11)	0.0581 (3)
H5	1.0830	0.3523	0.9902	0.070*
C6	0.80051 (19)	0.31483 (12)	0.96224 (9)	0.0447 (2)
C7	0.77651 (19)	0.44124 (13)	0.87988 (9)	0.0469 (2)
H7	0.8947	0.4911	0.8572	0.056*
C8	0.60545 (19)	0.49270 (12)	0.83399 (9)	0.0447 (2)
H8	0.4831	0.4467	0.8541	0.054*
C9	0.60632 (18)	0.62255 (12)	0.75108 (9)	0.0439 (2)
O1	0.74616 (16)	0.70168 (10)	0.73318 (8)	0.0600 (2)
N1	0.44089 (16)	0.65399 (10)	0.69570 (8)	0.0474 (2)
C10	0.2872 (2)	0.56144 (15)	0.69998 (10)	0.0537 (3)
H10	0.1398	0.6040	0.7155	0.064*
C11	0.3327 (2)	0.41992 (15)	0.68402 (10)	0.0545 (3)
H11	0.2124	0.3729	0.6941	0.065*
C12	0.5480 (2)	0.32715 (12)	0.65251 (9)	0.0472 (3)
C13	0.5818 (3)	0.17475 (15)	0.68682 (12)	0.0663 (4)
H13	0.4678	0.1327	0.7309	0.080*
C14	0.7817 (4)	0.08498 (16)	0.65648 (15)	0.0781 (5)
H14	0.8016	−0.0160	0.6811	0.094*
C15	0.9499 (3)	0.14446 (17)	0.59047 (15)	0.0727 (4)
H15	1.0847	0.0843	0.5707	0.087*
C16	0.9191 (3)	0.29425 (15)	0.55317 (12)	0.0622 (3)
H16	1.0325	0.3345	0.5071	0.075*
C17	0.7205 (2)	0.38448 (12)	0.58411 (10)	0.0512 (3)
H17	0.7019	0.4853	0.5588	0.061*
C18	0.4179 (3)	0.79342 (14)	0.62545 (12)	0.0628 (4)
H181	0.4671	0.8674	0.6533	0.094*
H182	0.2669	0.8259	0.6201	0.094*
H183	0.5048	0.7788	0.5567	0.094*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0516 (7)	0.0576 (7)	0.0575 (7)	−0.0127 (5)	−0.0159 (5)	0.0013 (5)
C2	0.0691 (9)	0.0633 (8)	0.0597 (7)	−0.0183 (7)	−0.0113 (6)	0.0071 (6)
C3	0.0761 (10)	0.0640 (8)	0.0494 (6)	−0.0032 (7)	−0.0156 (6)	0.0042 (5)
C4	0.0658 (9)	0.0725 (9)	0.0631 (8)	0.0005 (7)	−0.0303 (7)	−0.0012 (6)
C5	0.0509 (7)	0.0600 (7)	0.0658 (7)	−0.0082 (5)	−0.0226 (6)	−0.0014 (6)
C6	0.0418 (5)	0.0463 (5)	0.0444 (5)	−0.0025 (4)	−0.0094 (4)	−0.0067 (4)
C7	0.0399 (5)	0.0485 (5)	0.0513 (6)	−0.0071 (4)	−0.0105 (4)	−0.0027 (4)
C8	0.0412 (5)	0.0477 (5)	0.0451 (5)	−0.0077 (4)	−0.0099 (4)	−0.0039 (4)
C9	0.0391 (5)	0.0432 (5)	0.0478 (5)	−0.0020 (4)	−0.0096 (4)	−0.0061 (4)
O1	0.0524 (5)	0.0530 (5)	0.0762 (6)	−0.0151 (4)	−0.0203 (4)	0.0048 (4)
N1	0.0443 (5)	0.0433 (4)	0.0536 (5)	−0.0013 (4)	−0.0153 (4)	−0.0032 (4)
C10	0.0359 (5)	0.0669 (7)	0.0574 (6)	−0.0076 (5)	−0.0133 (4)	−0.0011 (5)
C11	0.0476 (6)	0.0678 (7)	0.0541 (6)	−0.0262 (5)	−0.0145 (5)	0.0017 (5)
C12	0.0575 (7)	0.0446 (5)	0.0454 (5)	−0.0206 (4)	−0.0164 (5)	0.0005 (4)
C13	0.0903 (11)	0.0509 (7)	0.0635 (8)	−0.0319 (7)	−0.0235 (7)	0.0119 (6)
C14	0.1117 (14)	0.0410 (6)	0.0849 (11)	−0.0077 (7)	−0.0405 (10)	0.0048 (6)
C15	0.0796 (11)	0.0546 (7)	0.0865 (11)	0.0040 (7)	−0.0314 (9)	−0.0155 (7)
C16	0.0612 (8)	0.0542 (7)	0.0714 (8)	−0.0118 (6)	−0.0074 (6)	−0.0135 (6)
C17	0.0578 (7)	0.0398 (5)	0.0557 (6)	−0.0146 (4)	−0.0066 (5)	−0.0036 (4)
C18	0.0745 (9)	0.0452 (6)	0.0685 (8)	0.0004 (6)	−0.0289 (7)	0.0005 (5)

Geometric parameters (Å, º) top

C1—C2	1.3798 (19)	N1—C18	1.4566 (16)
C1—C6	1.3896 (18)	C10—C11	1.3245 (19)
C1—H1	0.9300	C10—H10	0.9300
C2—C3	1.383 (2)	C11—C12	1.471 (2)
C2—H2	0.9300	C11—H11	0.9300
C3—C4	1.366 (2)	C12—C17	1.3902 (18)
C3—H3	0.9300	C12—C13	1.3960 (17)
C4—C5	1.386 (2)	C13—C14	1.384 (3)
C4—H4	0.9300	C13—H13	0.9300
C5—C6	1.3902 (17)	C14—C15	1.367 (3)
C5—H5	0.9300	C14—H14	0.9300
C6—C7	1.4611 (16)	C15—C16	1.381 (2)
C7—C8	1.3228 (16)	C15—H15	0.9300
C7—H7	0.9300	C16—C17	1.381 (2)
C8—C9	1.4797 (16)	C16—H16	0.9300
C8—H8	0.9300	C17—H17	0.9300
C9—O1	1.2254 (15)	C18—H181	0.9600
C9—N1	1.3621 (15)	C18—H182	0.9600
N1—C10	1.4133 (17)	C18—H183	0.9600

C2—C1—C6	120.79 (13)	C11—C10—N1	126.33 (11)
C2—C1—H1	119.6	C11—C10—H10	116.8
C6—C1—H1	119.6	N1—C10—H10	116.8
C1—C2—C3	120.35 (14)	C10—C11—C12	128.68 (11)
C1—C2—H2	119.8	C10—C11—H11	115.7
C3—C2—H2	119.8	C12—C11—H11	115.7
C4—C3—C2	119.77 (13)	C17—C12—C13	117.46 (13)
C4—C3—H3	120.1	C17—C12—C11	122.16 (11)
C2—C3—H3	120.1	C13—C12—C11	120.30 (12)
C3—C4—C5	120.01 (13)	C14—C13—C12	121.25 (14)
C3—C4—H4	120.0	C14—C13—H13	119.4
C5—C4—H4	120.0	C12—C13—H13	119.4
C4—C5—C6	121.19 (14)	C15—C14—C13	120.15 (13)
C4—C5—H5	119.4	C15—C14—H14	119.9
C6—C5—H5	119.4	C13—C14—H14	119.9
C1—C6—C5	117.88 (11)	C14—C15—C16	119.79 (16)
C1—C6—C7	123.17 (11)	C14—C15—H15	120.1
C5—C6—C7	118.95 (11)	C16—C15—H15	120.1
C8—C7—C6	127.28 (11)	C15—C16—C17	120.21 (15)
C8—C7—H7	116.4	C15—C16—H16	119.9
C6—C7—H7	116.4	C17—C16—H16	119.9
C7—C8—C9	120.86 (11)	C16—C17—C12	121.10 (12)
C7—C8—H8	119.6	C16—C17—H17	119.5
C9—C8—H8	119.6	C12—C17—H17	119.5
O1—C9—N1	120.39 (11)	N1—C18—H181	109.5
O1—C9—C8	122.32 (10)	N1—C18—H182	109.5
N1—C9—C8	117.28 (10)	H181—C18—H182	109.5
C9—N1—C10	125.32 (10)	N1—C18—H183	109.5
C9—N1—C18	118.41 (11)	H181—C18—H183	109.5
C10—N1—C18	116.27 (10)	H182—C18—H183	109.5

C6—C1—C2—C3	0.1 (2)	O1—C9—N1—C18	−7.99 (17)
C1—C2—C3—C4	0.5 (2)	C8—C9—N1—C18	170.62 (10)
C2—C3—C4—C5	−1.1 (2)	C9—N1—C10—C11	−53.69 (19)
C3—C4—C5—C6	1.1 (2)	C18—N1—C10—C11	126.00 (14)
C2—C1—C6—C5	−0.1 (2)	N1—C10—C11—C12	−3.9 (2)
C2—C1—C6—C7	−179.54 (12)	C10—C11—C12—C17	−34.6 (2)
C4—C5—C6—C1	−0.5 (2)	C10—C11—C12—C13	148.71 (14)
C4—C5—C6—C7	178.95 (12)	C17—C12—C13—C14	1.9 (2)
C1—C6—C7—C8	8.2 (2)	C11—C12—C13—C14	178.75 (13)
C5—C6—C7—C8	−171.22 (12)	C12—C13—C14—C15	−1.0 (2)
C6—C7—C8—C9	−179.88 (10)	C13—C14—C15—C16	−0.7 (3)
C7—C8—C9—O1	−11.86 (18)	C14—C15—C16—C17	1.3 (2)
C7—C8—C9—N1	169.57 (11)	C15—C16—C17—C12	−0.3 (2)
O1—C9—N1—C10	171.70 (11)	C13—C12—C17—C16	−1.29 (19)
C8—C9—N1—C10	−9.70 (17)	C11—C12—C17—C16	−178.04 (12)

Experimental details

Crystal data
Chemical formula	C₁₈H₁₇NO
M_r	263.33
Crystal system, space group	Triclinic, P1
Temperature (K)	298
a, b, c (Å)	6.356 (1), 9.265 (2), 13.073 (3)
α, β, γ (°)	80.45 (3), 77.22 (3), 78.13 (3)
V (Å³)	728.9 (3)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.07
Crystal size (mm)	0.60 × 0.60 × 0.55

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	25654, 5327, 3962
R_int	0.023
(sin θ/λ)_max (Å⁻¹)	0.772

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.060, 0.190, 1.02
No. of reflections	5327
No. of parameters	182
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.36, −0.14

Computer programs: SMART (Bruker, 2004), SAINT (Bruker, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEPIII (Burnett & Johnson, 1996) and SCHAKAL99 (Keller & Pierrard, 1999).

Acknowledgements

The authors wish to thank Dau Thi Kim Quyen MSc, Faculty of Chemistry, Vinh University, for help in sample preparation. The help of Stefan Mebs Dipl. Chem. in X-ray data collection is gratefully acknowledged.

References

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