7-Acetoxy-4-(1-chloro­ethyl)­coumarin

The title compound, C₁₃H₁₁ClO₄, a previously unknown coumarin, has the acetoxy and chloro­ethyl substituents aligned at angles of 65.76 (7) and 63.52 (9)°, respectively, from the plane of the coumarin rings.

Key indicators

• Single-crystal X-ray study
• T = 200 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.042
• wR factor = 0.118
• Data-to-parameter ratio = 12.2

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

---

S1. Comment

Coumarins are of considerable general importance (Campbell, 1959) and are prominent in natural products chemistry (Dean, 1963; Murray et al., 1982). They have been found to possess a wide variety of uses in the perfumery industry, as flavour enhancers, sunscreens, laser dyes (Khalfan et al., 1987) and in the pharmaceutical industry (Hooper et al., 1982; Morris & Russell, 1971). Our recent work showed pronounced activity of 4-methylcoumarins against Herpes simplex and Vascular stomatitis viruses (Parmar et al., 1996). Encouraged by these findings, we have synthesized a series of coumarins for structure–activity studies. This paper reports the synthesis and structure of the new coumarin, 7-acetoxy-4-(1-chloroethyl)coumarin, (I).

The molecular structure of (I) is illustrated in Fig. 1. A l l bond lengths and angles are largely unremarkable. The inclinations of the planes of the acetoxy and chloroethyl substituents (defined by the O3/C11/O4/C12 and Cl1/C1'/C2' atoms) with respect to the coumarin ring system are 65.76 (7) and 63.52 (9)°, respectively.

S2. Experimental

The previously unknown 4-(1-chloroethyl)-7-hydroxycoumarin, (II), was prepared by the addition of resorcinol (25.41 g, 0.231 mol) and ethyl 2-(2-chloropropionyl)-2-ethoxycarbonyl acetate (58.0 g, 0.231 mol) to ice-cooled concentrated H₂SO₄ (45 ml). The reaction mixture was maintained at room temperature for 20 h and ice-cooled water was added. (II) precipitated out, was filtered off and crystallized from alcohol as colourless needles (16.5 g, 32% yield), m.p. 429–431 K. The title compound (I) (560 mg, 91% yield) was obtained by the acetylation of (II) (500 mg, 0.228 mol) using acetic anhydride and pyridine. It crystallized from ethyl acetate/petroleum ether as colourless needles, m.p. 410 K.

S3. Refinement

The temperature of the crystal during the X-ray diffraction experiment was controlled using an Oxford Cryosystems Cryostream Cooler (Cosier & Glazer, 1986). H atoms were added at calculated positions and refined using a riding model. Anisotropic displacement parameters were used for all non-H atoms; H atoms were given isotropic displacement parameters equal to 1.2 (or 1.5 for methyl H atoms) times the equivalent isotropic displacement parameter of their parent atoms.

Computing details

Data collection: SMART (Siemens, 1994); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT; program(s) used to solve structure: SHELXTL/PC (Siemens, 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL/PC; software used to prepare material for publication: SHELXTL/PC.

Figures

Fig. 1. View of the title molecule showing the atomic numbering. Displacement ellipsoids are drawn at the 50% probability level for non-H atoms. H atoms are shown as spheres of arbitrary radii.

4-(1-Chloroethyl)coumarin-7-yl acetate

Crystal data

C13H11ClO4	Z = 2
Mr = 266.67	F(000) = 276
Triclinic, P1	Dx = 1.480 Mg m^−3
a = 4.1204 (6) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.7106 (17) Å	Cell parameters from 1852 reflections
c = 13.842 (2) Å	θ = 1.5–25.1°
α = 97.450 (4)°	µ = 0.32 mm^−1
β = 94.291 (4)°	T = 200 K
γ = 97.184 (4)°	Plate, colourless
V = 598.39 (16) Å^3	0.40 × 0.24 × 0.06 mm

Data collection

Siemens SMART CCD area-detector diffractometer	2010 independent reflections
Radiation source: normal-focus sealed tube	1570 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.017
Detector resolution: 8.192 pixels mm^-1	θmax = 25.1°, θmin = 1.5°
ω scans	h = −4→4
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −8→12
Tmin = 0.882, Tmax = 0.981	l = −16→13
2931 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.118	H-atom parameters constrained
S = 1.00	w = 1/[σ^2(Fo^2) + (0.0746P)^2] where P = (Fo^2 + 2Fc^2)/3
2010 reflections	(Δ/σ)max < 0.001
165 parameters	Δρmax = 0.27 e Å^−3
0 restraints	Δρmin = −0.22 e Å^−3

Special details

Experimental. Spectroscopic data: UV (MeOH) λ_max(nm): 317, 284 and 202; IR(KBr) ν_max/cm^-1: 2925, 2372, 1780, 1725, 1618, 1375, 1267, 1208, 1135, 1008, 879, 722, 652 and 608; ¹H NMR (300 MHz, CDCl₃): δ 1.91 (3H, d, J = 6.7 Hz, C-2'H), 2.34 (3H, s, OCOCH₃), 5.26 (1H, q, J = 6.7 Hz, C-1'H), 6.59 (1H, s, C-3H), 7.11 (1H, dd, J = 8.7 Hz, J = 2.2 Hz, C-6H), 7.16 (1H, d, J = 2.2 Hz, C-8H) and 7.75 (1H, d, J = 8.7 Hz, C-5H); ¹³C NMR (75 MHz, CDCl₃): δ 21.52 (C-2'), 23.97 (CH₃CO), 51.76 (C-1'), 111.37, 113.24, 118.73 and 125.61 (C-3, C-6, C-8, and C-10), 153.64, 154.16 and 155.03 (C-4, C-5, C-7 and C-9), 160.77 (C-2) and 169.03 (CH₃CO); EIMS, m/z (% rel. int.): 267 [M⁺](10), 224 (24), 196 (11), 189 (18), 161 (100), 149 (4), 139 (4), 131 (16), 115 (14), 103 (32), 89 (15), 77 (37), 63(250 and 51 (31).

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
Cl1	0.14201 (15)	0.53214 (6)	0.35411 (5)	0.0381 (2)
O1	0.1272 (4)	0.97031 (15)	0.23696 (11)	0.0313 (4)
O2	−0.0669 (4)	1.06399 (17)	0.36699 (12)	0.0424 (5)
O3	0.5333 (4)	0.79658 (17)	−0.05180 (11)	0.0380 (5)
O4	0.1831 (6)	0.6210 (2)	−0.10865 (14)	0.0648 (7)
C2	0.0688 (6)	0.9766 (2)	0.33315 (17)	0.0301 (6)
C3	0.1717 (5)	0.8785 (2)	0.38602 (17)	0.0288 (5)
H3A	0.1405	0.8829	0.4536	0.035*
C4	0.3103 (5)	0.7809 (2)	0.34296 (16)	0.0255 (5)
C5	0.5160 (5)	0.6815 (2)	0.18604 (17)	0.0307 (6)
H5A	0.5829	0.6136	0.2170	0.037*
C6	0.5667 (6)	0.6851 (2)	0.08929 (17)	0.0324 (6)
H6A	0.6660	0.6205	0.0536	0.039*
C7	0.4696 (6)	0.7850 (2)	0.04503 (16)	0.0321 (6)
C8	0.3268 (6)	0.8801 (2)	0.09454 (16)	0.0311 (6)
H8A	0.2641	0.9484	0.0631	0.037*
C9	0.2770 (5)	0.8737 (2)	0.19140 (16)	0.0270 (5)
C10	0.3681 (5)	0.7755 (2)	0.24028 (16)	0.0255 (5)
C11	0.3726 (6)	0.7071 (2)	−0.12457 (17)	0.0355 (6)
C12	0.4652 (7)	0.7363 (3)	−0.22172 (18)	0.0429 (7)
H12A	0.4231	0.6585	−0.2691	0.064*
H12B	0.6990	0.7701	−0.2166	0.064*
H12C	0.3344	0.7996	−0.2435	0.064*
C1'	0.4119 (5)	0.6784 (2)	0.39946 (16)	0.0281 (5)
H1'A	0.6398	0.6650	0.3845	0.034*
C2'	0.4116 (6)	0.7044 (2)	0.50969 (16)	0.0332 (6)
H2'A	0.5541	0.7841	0.5346	0.050*
H2'B	0.4934	0.6345	0.5391	0.050*
H2'C	0.1873	0.7114	0.5267	0.050*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0396 (4)	0.0272 (4)	0.0482 (4)	0.0074 (3)	0.0032 (3)	0.0050 (3)
O1	0.0395 (9)	0.0274 (9)	0.0290 (10)	0.0105 (8)	0.0046 (7)	0.0050 (7)
O2	0.0588 (12)	0.0343 (11)	0.0387 (10)	0.0221 (9)	0.0111 (9)	0.0037 (8)
O3	0.0516 (11)	0.0362 (10)	0.0238 (9)	−0.0028 (8)	0.0074 (8)	0.0022 (7)
O4	0.0863 (16)	0.0591 (15)	0.0378 (12)	−0.0275 (13)	−0.0014 (10)	0.0054 (10)
C2	0.0342 (13)	0.0251 (13)	0.0301 (13)	0.0034 (11)	0.0034 (10)	0.0008 (10)
C3	0.0308 (12)	0.0317 (13)	0.0243 (12)	0.0050 (11)	0.0027 (10)	0.0043 (10)
C4	0.0204 (11)	0.0270 (13)	0.0283 (12)	0.0024 (10)	−0.0001 (9)	0.0032 (10)
C5	0.0311 (12)	0.0294 (14)	0.0314 (14)	0.0059 (11)	0.0005 (10)	0.0033 (10)
C6	0.0349 (13)	0.0334 (14)	0.0284 (13)	0.0062 (11)	0.0052 (10)	−0.0007 (11)
C7	0.0323 (13)	0.0356 (15)	0.0256 (13)	−0.0039 (11)	0.0027 (10)	0.0016 (11)
C8	0.0367 (13)	0.0268 (13)	0.0294 (13)	0.0028 (11)	−0.0001 (10)	0.0048 (10)
C9	0.0262 (12)	0.0247 (12)	0.0287 (13)	0.0035 (10)	0.0003 (9)	0.0000 (10)
C10	0.0232 (11)	0.0272 (13)	0.0252 (12)	0.0029 (10)	−0.0010 (9)	0.0028 (10)
C11	0.0444 (15)	0.0304 (15)	0.0308 (15)	0.0070 (12)	0.0022 (11)	0.0002 (11)
C12	0.0577 (17)	0.0417 (17)	0.0290 (14)	0.0082 (14)	0.0069 (12)	0.0005 (12)
C1'	0.0260 (12)	0.0299 (13)	0.0296 (13)	0.0073 (10)	0.0028 (10)	0.0045 (10)
C2'	0.0403 (13)	0.0377 (15)	0.0249 (13)	0.0149 (12)	0.0008 (10)	0.0083 (11)

Geometric parameters (Å, º)

Cl1—C1'	1.814 (2)	C6—C7	1.386 (4)
O1—C2	1.365 (3)	C6—H6A	0.950
O1—C9	1.378 (3)	C7—C8	1.372 (3)
O2—C2	1.210 (3)	C8—C9	1.381 (3)
O3—C11	1.365 (3)	C8—H8A	0.9500
O3—C7	1.403 (3)	C9—C10	1.396 (3)
O4—C11	1.186 (3)	C11—C12	1.486 (3)
C2—C3	1.444 (3)	C12—H12A	0.980
C3—C4	1.346 (3)	C12—H12B	0.980
C3—H3A	0.950	C12—H12C	0.980
C4—C10	1.454 (3)	C1'—C2'	1.515 (3)
C4—C1'	1.510 (3)	C1'—H1'A	1.000
C5—C6	1.375 (3)	C2'—H2'A	0.980
C5—C10	1.405 (3)	C2'—H2'B	0.980
C5—H5A	0.950	C2'—H2'C	0.980
C2—O1—C9	121.49 (18)	C8—C9—C10	122.7 (2)
C11—O3—C7	118.12 (19)	C9—C10—C5	116.7 (2)
O2—C2—O1	117.1 (2)	C9—C10—C4	117.6 (2)
O2—C2—C3	125.3 (2)	C5—C10—C4	125.7 (2)
O1—C2—C3	117.6 (2)	O4—C11—O3	122.4 (2)
C4—C3—C2	122.4 (2)	O4—C11—C12	127.1 (2)
C4—C3—H3A	118.8	O3—C11—C12	110.5 (2)
C2—C3—H3A	118.8	C11—C12—H12A	109.5
C3—C4—C10	119.1 (2)	C11—C12—H12B	109.5
C3—C4—C1'	121.4 (2)	H12A—C12—H12B	109.5
C10—C4—C1'	119.45 (19)	C11—C12—H12C	109.5
C6—C5—C10	121.8 (2)	H12A—C12—H12C	109.5
C6—C5—H5A	119.1	H12B—C12—H12C	109.5
C10—C5—H5A	119.1	C4—C1'—C2'	116.3 (2)
C5—C6—C7	118.5 (2)	C4—C1'—Cl1	108.00 (15)
C5—C6—H6A	120.7	C2'—C1'—Cl1	109.01 (17)
C7—C6—H6A	120.7	C4—C1'—H1'A	107.7
C8—C7—C6	122.2 (2)	C2'—C1'—H1'A	107.7
C8—C7—O3	117.1 (2)	Cl1—C1'—H1'A	107.7
C6—C7—O3	120.5 (2)	C1'—C2'—H2'A	109.5
C7—C8—C9	118.0 (2)	C1'—C2'—H2'B	109.5
C7—C8—H8A	121.0	H2'A—C2'—H2'B	109.5
C9—C8—H8A	121.0	C1'—C2'—H2'C	109.5
O1—C9—C8	115.5 (2)	H2'A—C2'—H2'C	109.5
O1—C9—C10	121.8 (2)	H2'B—C2'—H2'C	109.5
C9—O1—C2—O2	−179.3 (2)	O1—C9—C10—C5	179.36 (19)
C9—O1—C2—C3	0.4 (3)	C8—C9—C10—C5	0.1 (3)
O2—C2—C3—C4	177.4 (2)	O1—C9—C10—C4	−2.2 (3)
O1—C2—C3—C4	−2.3 (3)	C8—C9—C10—C4	178.5 (2)
C2—C3—C4—C10	1.9 (3)	C6—C5—C10—C9	−0.5 (3)
C2—C3—C4—C1'	−179.2 (2)	C6—C5—C10—C4	−178.8 (2)
C10—C5—C6—C7	0.3 (4)	C3—C4—C10—C9	0.4 (3)
C5—C6—C7—C8	0.3 (4)	C1'—C4—C10—C9	−178.62 (19)
C5—C6—C7—O3	176.3 (2)	C3—C4—C10—C5	178.6 (2)
C11—O3—C7—C8	−116.4 (2)	C1'—C4—C10—C5	−0.4 (3)
C11—O3—C7—C6	67.4 (3)	C7—O3—C11—O4	0.1 (4)
C6—C7—C8—C9	−0.7 (3)	C7—O3—C11—C12	178.8 (2)
O3—C7—C8—C9	−176.9 (2)	C3—C4—C1'—C2'	−11.5 (3)
C2—O1—C9—C8	−178.82 (19)	C10—C4—C1'—C2'	167.4 (2)
C2—O1—C9—C10	1.8 (3)	C3—C4—C1'—Cl1	111.3 (2)
C7—C8—C9—O1	−178.82 (19)	C10—C4—C1'—Cl1	−69.7 (2)
C7—C8—C9—C10	0.5 (3)