Methyl 3-(4-fluoro­phen­yl)-1-methyl-1,2,3,3a,4,9b-hexa­hydro­chromeno[4,3-b]pyrrole-3a-carboxyl­ate

Abstract

In the title compound, C₂₀H₂₀FNO₃, the pyrrolidine and benzopyran rings adopt half chair and twisted half chair conformations, respectively. The carboxyl­ate group is almost perpendicular to the pyran ring [89.4 (1)°].

Related literature

Chromanone derivatives are used as inter­mediates in the synthesis of natural products calonlide (A) and inophyllum (B) (Ellis et al., 1977 ▶), which have been suggested to have activity against anti-human immuno deficiency virus type 1 (HIV-1) (Hussain & Amir, 1986 ▶). Chromanone derivatives dilate the heart and act as remedies for angina pectoris, see: Hasegnaida (1967 ▶). Pyrrolidine derivatives possess anti-influenza (Stylianakis et al., 2003 ▶) and anti-convulsant (Obniska et al., 2002 ▶) activity. For related structures, see: Abdul Ajees et al. (2002 ▶); Usha et al. (2003 ▶). For asymmetry parameters, see: Nardelli (1983 ▶).

Experimental

Crystal data

• C₂₀H₂₀FNO₃

• M _r = 341.37

• Monoclinic,

• a = 10.4519 (4) Å

• b = 20.6778 (8) Å

• c = 7.8508 (3) Å

• β = 91.535 (2)°

• V = 1696.12 (11) ų

• Z = 4

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 293 K

• 0.22 × 0.20 × 0.19 mm

Data collection

• Bruker Kappa APEXII CCD diffractometer

• 16737 measured reflections

• 4237 independent reflections

• 2844 reflections with I > 2σ(I)

• R _int = 0.035

Refinement

• R[F ² > 2σ(F ²)] = 0.045

• wR(F ²) = 0.219

• S = 0.81

• 4237 reflections

• 227 parameters

• H-atom parameters constrained

• Δρ_max = 0.24 e Å⁻³

• Δρ_min = −0.18 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT and XPREP (Bruker, 2004 ▶); program(s) used to solve structure: SHELXS97(Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

Chromanone derivatives are used as a varsatile intermediate in the synthesis of natural products calonlide(A) and inophyllum(B), (Ellis et al., 1977) which have been suggested to have activity against anti-human immuno deficiency virus type1 (HIV-1) (Hussain et al., 1986). Chromanone derivatives dilate the heart and act as remedies for angina pectoris (Hasegnaida, 1967). Spiropyrrolidine derivatives are often used in the synthesis of biologically active compounds. Spiro ring system is also very interesting from a biogenetic point of view. Synthetic pyrrolidine derivatives have activity against the aldose reductase enzyme, which controls influenza. Pyrrolidine derivatives possess anti-influenza (Stylianakis et al., 2003) and anti- convulsant (Obniska et al., 2002) activity. We report here the crystal structure of the title compound, Fig.1. The C—C, N—C, C—O bond lengths in the structure are close to those found in the related structures (Usha et al., 2003; Abdul Ajees et al., 2002). The sum of the angle around atom N (332°) indicates sp³ hybridization. The carboxylate group is perpendicular to the pyran ring [89.4 (1)°].The pyran ring adopts twist-half chair conformation with lowest asymmetry parameters (Nardelli, 1983) of Δ (C9—C5) =0.033 (1) and the pyrrole ring adopts half chair conformation Δs(C8) = 0.008 (1). The molecular conformation is stabilizaed by two weak C—H···N and C—H···O intramolecular interactions, Table 1. The crystal packing is stabilized by van der Waals forces.

Experimental

A mixture of (E)-methyl2-((2-formylphenoxy) methyl)-3-(4-fluorophenyl)acrylate(2 mmol) and sarcosine (2 mmol) in acetonitrile (8 ml) was refluxed for 5h. After the completion of the reaction mixture was concentrated and the resulting crude mass was diluted with water (15 ml). The combined organic layer was washed with brine (2x10ml) and dried over anhydrous Na₂SO_4.The organic layer was concentrated and purified by column chromatographyon silica gel (Acme 100–200 mesh), using ethyl acetate-hexanes (1:9) to afford the pure title of the compound as a colourless solid in 65% yield.

Refinement

The H atoms were positioned geometrically and were treated as riding on their parent C atoms, with aromatic C—H = 0.93Å , methyl C-H = 0.96Å and methylene C—H = 0.97Å and with U_iso = 1.5U_eq(C) for methyl H and 1.2U_eq(C) for the remaining H atoms.

Figures

Fig. 1.

The molecular structure of the title compound, with displacement ellipsoids drawn at the 30% probability level.

Crystal data

C20H20FNO3	F(000) = 720
Mr = 341.37	Dx = 1.337 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 4237 reflections
a = 10.4519 (4) Å	θ = 2–28°
b = 20.6778 (8) Å	µ = 0.10 mm−1
c = 7.8508 (3) Å	T = 293 K
β = 91.535 (2)°	Block, colourless
V = 1696.12 (11) Å3	0.22 × 0.20 × 0.19 mm
Z = 4

Data collection

Bruker Kappa APEXII CCD diffractometer	2844 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.035
graphite	θmax = 28.4°, θmin = 2.0°
ω and φ scan	h = −13→13
16737 measured reflections	k = −27→27
4237 independent reflections	l = −10→10

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.045	H-atom parameters constrained
wR(F2) = 0.219	w = 1/[σ2(Fo2) + (0.2P)2] where P = (Fo2 + 2Fc2)/3
S = 0.81	(Δ/σ)max < 0.001
4237 reflections	Δρmax = 0.24 e Å−3
227 parameters	Δρmin = −0.18 e Å−3
0 restraints	Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 constraints	Extinction coefficient: 0.013 (4)
Primary atom site location: structure-invariant direct methods

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
C20	0.1861 (2)	0.22098 (11)	0.9717 (3)	0.0645 (6)
H20A	0.1703	0.2651	0.9389	0.097*
H20B	0.2338	0.2201	1.0780	0.097*
H20C	0.1060	0.1990	0.9845	0.097*
O1	0.53935 (13)	0.05675 (7)	0.87998 (17)	0.0559 (4)
F	−0.01102 (13)	−0.15643 (6)	0.7317 (2)	0.0775 (5)
C1	0.63732 (18)	0.20543 (10)	0.6667 (2)	0.0505 (5)
H1	0.6080	0.2352	0.5858	0.061*
C2	0.7536 (2)	0.21569 (12)	0.7493 (3)	0.0655 (6)
H2	0.8025	0.2518	0.7236	0.079*
C3	0.7969 (2)	0.17199 (14)	0.8701 (3)	0.0737 (7)
H3	0.8757	0.1785	0.9253	0.088*
C4	0.7248 (2)	0.11893 (12)	0.9099 (3)	0.0640 (6)
H4	0.7545	0.0898	0.9922	0.077*
C5	0.60721 (17)	0.10867 (9)	0.8271 (2)	0.0458 (4)
C6	0.42920 (17)	0.03806 (8)	0.7786 (2)	0.0422 (4)
H6A	0.3763	0.0094	0.8447	0.051*
H6B	0.4569	0.0143	0.6796	0.051*
C7	0.35015 (15)	0.09573 (8)	0.72016 (18)	0.0357 (4)
C8	0.43498 (15)	0.14033 (8)	0.61491 (19)	0.0359 (4)
H8	0.3916	0.1818	0.5955	0.043*
C9	0.56300 (16)	0.15160 (8)	0.7018 (2)	0.0398 (4)
C10	0.24295 (16)	0.07657 (8)	0.58563 (19)	0.0383 (4)
H10	0.1776	0.1105	0.5884	0.046*
C11	0.30986 (18)	0.08318 (10)	0.4144 (2)	0.0485 (5)
H11A	0.3104	0.0420	0.3554	0.058*
H11B	0.2657	0.1146	0.3425	0.058*
C12	0.17597 (15)	0.01306 (8)	0.62225 (18)	0.0373 (4)
C13	0.06850 (16)	0.01298 (9)	0.7231 (2)	0.0440 (4)
H13	0.0382	0.0520	0.7649	0.053*
C14	0.00570 (18)	−0.04361 (10)	0.7628 (2)	0.0515 (5)
H14	−0.0650	−0.0433	0.8323	0.062*
C15	0.05039 (18)	−0.09990 (9)	0.6970 (2)	0.0503 (5)
C16	0.1548 (2)	−0.10261 (9)	0.5965 (3)	0.0540 (5)
H16	0.1828	−0.1418	0.5532	0.065*
C17	0.21785 (17)	−0.04557 (9)	0.5604 (2)	0.0475 (4)
H17	0.2898	−0.0467	0.4932	0.057*
C18	0.49406 (18)	0.14114 (10)	0.3144 (2)	0.0501 (5)
H18A	0.4949	0.1146	0.2141	0.075*
H18B	0.5799	0.1542	0.3444	0.075*
H18C	0.4424	0.1788	0.2925	0.075*
C19	0.28728 (16)	0.12722 (8)	0.87041 (19)	0.0397 (4)
N	0.44108 (14)	0.10458 (7)	0.45389 (16)	0.0395 (4)
O2	0.25895 (16)	0.09942 (7)	0.99746 (16)	0.0637 (5)
O3	0.25839 (14)	0.18923 (6)	0.84246 (17)	0.0556 (4)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C20	0.0666 (14)	0.0625 (13)	0.0655 (13)	0.0059 (10)	0.0216 (11)	−0.0122 (10)
O1	0.0514 (8)	0.0618 (8)	0.0535 (8)	−0.0039 (6)	−0.0194 (6)	0.0170 (6)
F	0.0686 (9)	0.0619 (8)	0.1021 (11)	−0.0257 (6)	0.0022 (8)	0.0114 (7)
C1	0.0503 (10)	0.0546 (11)	0.0470 (10)	−0.0087 (8)	0.0096 (8)	−0.0091 (8)
C2	0.0541 (12)	0.0807 (15)	0.0623 (13)	−0.0264 (11)	0.0128 (10)	−0.0206 (11)
C3	0.0476 (12)	0.111 (2)	0.0623 (14)	−0.0190 (13)	−0.0064 (10)	−0.0203 (13)
C4	0.0501 (12)	0.0916 (17)	0.0497 (11)	−0.0018 (11)	−0.0114 (9)	−0.0022 (10)
C5	0.0411 (9)	0.0571 (11)	0.0391 (9)	0.0006 (8)	−0.0026 (7)	−0.0023 (7)
C6	0.0451 (9)	0.0424 (9)	0.0387 (8)	−0.0015 (7)	−0.0065 (7)	0.0064 (6)
C7	0.0374 (8)	0.0414 (9)	0.0281 (7)	−0.0010 (6)	−0.0008 (6)	0.0035 (6)
C8	0.0375 (8)	0.0386 (8)	0.0316 (7)	0.0014 (6)	0.0028 (6)	0.0048 (6)
C9	0.0382 (9)	0.0447 (10)	0.0364 (8)	−0.0022 (7)	0.0028 (7)	−0.0052 (6)
C10	0.0396 (8)	0.0442 (9)	0.0309 (8)	−0.0015 (7)	−0.0031 (6)	0.0040 (6)
C11	0.0512 (10)	0.0646 (12)	0.0294 (8)	−0.0137 (9)	−0.0015 (7)	0.0043 (7)
C12	0.0343 (8)	0.0473 (10)	0.0300 (7)	−0.0023 (7)	−0.0021 (6)	0.0005 (6)
C13	0.0386 (9)	0.0537 (11)	0.0398 (9)	−0.0001 (7)	0.0023 (7)	−0.0068 (7)
C14	0.0385 (9)	0.0679 (13)	0.0481 (10)	−0.0096 (8)	0.0047 (8)	−0.0005 (8)
C15	0.0448 (10)	0.0505 (11)	0.0554 (11)	−0.0122 (8)	−0.0055 (8)	0.0064 (8)
C16	0.0533 (11)	0.0453 (11)	0.0632 (12)	0.0009 (8)	−0.0009 (9)	−0.0061 (8)
C17	0.0401 (9)	0.0540 (11)	0.0486 (10)	0.0000 (8)	0.0077 (7)	−0.0046 (8)
C18	0.0481 (10)	0.0679 (12)	0.0345 (8)	−0.0039 (9)	0.0060 (7)	0.0094 (8)
C19	0.0403 (9)	0.0481 (10)	0.0305 (8)	−0.0058 (7)	−0.0014 (6)	0.0015 (7)
N	0.0420 (8)	0.0486 (8)	0.0280 (6)	−0.0016 (6)	0.0018 (5)	0.0029 (5)
O2	0.0889 (12)	0.0667 (10)	0.0364 (7)	0.0026 (7)	0.0172 (7)	0.0078 (6)
O3	0.0688 (9)	0.0489 (8)	0.0502 (7)	0.0061 (6)	0.0222 (6)	0.0000 (6)

Geometric parameters (Å, °)

C20—O3	1.440 (2)	C8—C9	1.504 (2)
C20—H20A	0.9600	C8—H8	0.9800
C20—H20B	0.9600	C10—C12	1.519 (2)
C20—H20C	0.9600	C10—C11	1.538 (2)
O1—C5	1.358 (2)	C10—H10	0.9800
O1—C6	1.435 (2)	C11—N	1.466 (2)
F—C15	1.364 (2)	C11—H11A	0.9700
C1—C2	1.379 (3)	C11—H11B	0.9700
C1—C9	1.389 (2)	C12—C17	1.382 (3)
C1—H1	0.9300	C12—C13	1.392 (2)
C2—C3	1.378 (4)	C13—C14	1.381 (3)
C2—H2	0.9300	C13—H13	0.9300
C3—C4	1.371 (4)	C14—C15	1.361 (3)
C3—H3	0.9300	C14—H14	0.9300
C4—C5	1.391 (3)	C15—C16	1.365 (3)
C4—H4	0.9300	C16—C17	1.384 (3)
C5—C9	1.395 (3)	C16—H16	0.9300
C6—C7	1.515 (2)	C17—H17	0.9300
C6—H6A	0.9700	C18—N	1.453 (2)
C6—H6B	0.9700	C18—H18A	0.9600
C7—C19	1.513 (2)	C18—H18B	0.9600
C7—C8	1.536 (2)	C18—H18C	0.9600
C7—C10	1.570 (2)	C19—O2	1.1953 (19)
C8—N	1.467 (2)	C19—O3	1.334 (2)
O3—C20—H20A	109.5	C12—C10—C11	117.71 (14)
O3—C20—H20B	109.5	C12—C10—C7	114.52 (12)
H20A—C20—H20B	109.5	C11—C10—C7	103.45 (12)
O3—C20—H20C	109.5	C12—C10—H10	106.8
H20A—C20—H20C	109.5	C11—C10—H10	106.8
H20B—C20—H20C	109.5	C7—C10—H10	106.8
C5—O1—C6	117.45 (13)	N—C11—C10	106.67 (12)
C2—C1—C9	121.4 (2)	N—C11—H11A	110.4
C2—C1—H1	119.3	C10—C11—H11A	110.4
C9—C1—H1	119.3	N—C11—H11B	110.4
C3—C2—C1	119.4 (2)	C10—C11—H11B	110.4
C3—C2—H2	120.3	H11A—C11—H11B	108.6
C1—C2—H2	120.3	C17—C12—C13	117.85 (16)
C2—C3—C4	120.6 (2)	C17—C12—C10	122.69 (15)
C2—C3—H3	119.7	C13—C12—C10	119.46 (15)
C4—C3—H3	119.7	C14—C13—C12	121.66 (17)
C3—C4—C5	119.9 (2)	C14—C13—H13	119.2
C3—C4—H4	120.0	C12—C13—H13	119.2
C5—C4—H4	120.0	C15—C14—C13	117.96 (16)
O1—C5—C4	116.08 (17)	C15—C14—H14	121.0
O1—C5—C9	123.58 (16)	C13—C14—H14	121.0
C4—C5—C9	120.30 (18)	C14—C15—C16	122.85 (17)
O1—C6—C7	112.27 (14)	C14—C15—F	119.26 (17)
O1—C6—H6A	109.1	C16—C15—F	117.89 (17)
C7—C6—H6A	109.1	C15—C16—C17	118.42 (17)
O1—C6—H6B	109.1	C15—C16—H16	120.8
C7—C6—H6B	109.1	C17—C16—H16	120.8
H6A—C6—H6B	107.9	C12—C17—C16	121.23 (17)
C19—C7—C6	110.33 (13)	C12—C17—H17	119.4
C19—C7—C8	115.48 (13)	C16—C17—H17	119.4
C6—C7—C8	108.52 (13)	N—C18—H18A	109.5
C19—C7—C10	108.43 (13)	N—C18—H18B	109.5
C6—C7—C10	112.26 (13)	H18A—C18—H18B	109.5
C8—C7—C10	101.62 (12)	N—C18—H18C	109.5
N—C8—C9	114.21 (13)	H18A—C18—H18C	109.5
N—C8—C7	101.54 (12)	H18B—C18—H18C	109.5
C9—C8—C7	111.63 (13)	O2—C19—O3	122.65 (16)
N—C8—H8	109.7	O2—C19—C7	124.48 (17)
C9—C8—H8	109.7	O3—C19—C7	112.74 (13)
C7—C8—H8	109.7	C18—N—C8	114.43 (14)
C1—C9—C5	118.24 (16)	C18—N—C11	111.78 (13)
C1—C9—C8	122.01 (16)	C8—N—C11	105.79 (13)
C5—C9—C8	119.69 (15)	C19—O3—C20	116.29 (15)
C9—C1—C2—C3	−0.5 (3)	C8—C7—C10—C11	26.42 (16)
C1—C2—C3—C4	−0.6 (4)	C12—C10—C11—N	−127.87 (15)
C2—C3—C4—C5	0.4 (4)	C7—C10—C11—N	−0.45 (18)
C6—O1—C5—C4	−169.32 (16)	C11—C10—C12—C17	31.4 (2)
C6—O1—C5—C9	12.9 (3)	C7—C10—C12—C17	−90.51 (19)
C3—C4—C5—O1	−176.91 (19)	C11—C10—C12—C13	−149.15 (15)
C3—C4—C5—C9	1.0 (3)	C7—C10—C12—C13	88.96 (18)
C5—O1—C6—C7	−42.6 (2)	C17—C12—C13—C14	0.8 (2)
O1—C6—C7—C19	−68.27 (17)	C10—C12—C13—C14	−178.74 (15)
O1—C6—C7—C8	59.16 (17)	C12—C13—C14—C15	−1.4 (3)
O1—C6—C7—C10	170.67 (13)	C13—C14—C15—C16	0.9 (3)
C19—C7—C8—N	−160.23 (13)	C13—C14—C15—F	−178.91 (17)
C6—C7—C8—N	75.34 (14)	C14—C15—C16—C17	0.1 (3)
C10—C7—C8—N	−43.13 (15)	F—C15—C16—C17	179.98 (17)
C19—C7—C8—C9	77.68 (16)	C13—C12—C17—C16	0.4 (3)
C6—C7—C8—C9	−46.75 (17)	C10—C12—C17—C16	179.85 (16)
C10—C7—C8—C9	−165.22 (13)	C15—C16—C17—C12	−0.8 (3)
C2—C1—C9—C5	1.8 (3)	C6—C7—C19—O2	−28.0 (2)
C2—C1—C9—C8	178.95 (16)	C8—C7—C19—O2	−151.46 (17)
O1—C5—C9—C1	175.64 (16)	C10—C7—C19—O2	95.34 (19)
C4—C5—C9—C1	−2.1 (3)	C6—C7—C19—O3	156.20 (14)
O1—C5—C9—C8	−1.5 (3)	C8—C7—C19—O3	32.72 (18)
C4—C5—C9—C8	−179.23 (16)	C10—C7—C19—O3	−80.49 (16)
N—C8—C9—C1	88.40 (19)	C9—C8—N—C18	−71.69 (18)
C7—C8—C9—C1	−157.13 (15)	C7—C8—N—C18	168.03 (13)
N—C8—C9—C5	−94.54 (18)	C9—C8—N—C11	164.82 (14)
C7—C8—C9—C5	19.9 (2)	C7—C8—N—C11	44.53 (15)
C19—C7—C10—C12	−82.09 (17)	C10—C11—N—C18	−152.67 (15)
C6—C7—C10—C12	40.05 (19)	C10—C11—N—C8	−27.52 (18)
C8—C7—C10—C12	155.80 (13)	O2—C19—O3—C20	−2.3 (3)
C19—C7—C10—C11	148.52 (14)	C7—C19—O3—C20	173.64 (16)
C6—C7—C10—C11	−89.33 (16)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6B···N	0.97	2.58	2.902 (2)	100
C8—H8···O3	0.98	2.42	2.792 (2)	102