3-(2-Bromo­acet­yl)phenyl benzoate

In the title compound, C₁₅H₁₁BrO₃, the dihedral angle between the benzene rings is 72.59 (6)°. In the crystal, pairs of C—H...π contacts form inversion dimers. Additional C—H...O hydrogen bonds generate R₂¹(6) ring motifs and stack these dimers along the b axis. Short inter­molecular Br...O contacts of 3.254 (3) Å are also observed and link the stacks into a three-dimensional network.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.033
• wR factor = 0.092
• Data-to-parameter ratio = 13.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT431_ALERT_2_C Short Inter HL..A  Contact  Br1    ..  O3      .       3.25 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H4     ..  O3      ..       2.70 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H1B    ..  O3      ..       2.65 Ang.
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.595          4

Alert level G
PLAT005_ALERT_5_G No _iucr_refine_instructions_details  in the CIF          ?
PLAT128_ALERT_4_G Alternate Setting of Space-group P21/c   .......      P21/n
PLAT909_ALERT_3_G Percentage of Observed Data at Theta(Max) still          62 Perc.
PLAT961_ALERT_5_G Dataset Contains no Negative Intensities .......          !

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   4 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   4 ALERT level G = General information/check it is not something unexpected

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   2 ALERT type 5 Informative message, check

---

S1. Comment

3-(2-bromoacetyl)phenyl benzoate is key starting material for the synthesis of phenylephrine, (R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol. Phenylephrine is a selective α₁-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupils, and to increase blood pressure.

Oral phenylephrine is extensively metabolized by monoamine oxidase (Naoto et al., 2008), an enzyme that is present in the gastrointestinal tract and in the liver. Therefore, compared to intravenous pseudoephedrine, it has a reduced and variable bioavailability, only up to 38% (Shwu-Jiuan & Mei-Hua, 1984; Jaakko & Erkki, 1959). Because phenylephrine is a directly selective α-adrenergic receptor agonist, it does not cause the release of endogenous noradrenaline, as pseudoephedrine does. Therefore, phenylephrine is less likely to cause side effects such as central nervous system stimulation, insomnia, anxiety, irritability, and restlessness (Junichi et al., 1956). Phenylephrine's effectiveness as a decongestant stems from its vasoconstriction of nasal blood vessels, thereby decreasing blood flow to the sinusoidal vessels, leading to decreased mucosal edema (D'Amico et al., 1956).

The asymmetric unit of 3-(2-bromoacetylphenyl benzoate is shown in Fig. 1. The dihedral angle between two (C3–C8) and (C10—C15) benzene rings is 72.59 (6)°. In the crystal structure a pair of C6—H6···π [C_g(2)(C10–C15) contacts form inversion dimers. Additional C4—H4···O3 and C1—H1B···O3 (Table.1) hydrogen bonds generate R¹₂(6) ring motifs (Bernstein et al., 1995) and stack these dimers along the b axis (Fig. 2). Short intermolecular Br1···O2 contacts, 3.254 (3) Å are also observed and link the stacks into a three dimensional network.

Related literature

For the biological applications and synthesis of the title compound, see: Naoto et al. (2008); Shwu-Jiuan & Mei-Hua (1984); Jaakko & Erkki (1959); Junichi et al. (1956); D'Amico et al. (1956). For hydrogen-bond motifs, see: Bernstein et al. (1995)

S2. Experimental

All the chemicals used were of analytical reagent grade and were used directly without further purification. The title compound was synthesized according to an already reported method (Shwu-Jiuan & Mei-Hua, 1984). The crude product was recrystallized from an ethanol/chloroform mixture, to give colourless crystals in 78% yield.

S3. Refinement

All H atoms were positioned geometrically, with C—H = 0.93 Å for aromatic H and C—H = 0.97 Å for methylene H and refined using a riding model with U_iso(H) = 1.2U_eq(C) for aromatic and methylene H.

Computing details

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); 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, 2012); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms are shown as spheres of arbitrary radius.
	Fig. 2. Crystal packing along b axis for the title compound with hydrogen bonds drawn as dashed lines.

3-(2-Bromoacetyl)phenyl benzoate

Crystal data

C15H11BrO3	F(000) = 640
Mr = 319.15	Dx = 1.596 Mg m^−3
Monoclinic, P21/n	Melting point: 378 K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 12.5055 (4) Å	Cell parameters from 2344 reflections
b = 5.4409 (2) Å	θ = 1.9–25.0°
c = 19.5178 (6) Å	µ = 3.10 mm^−1
β = 90.859 (2)°	T = 296 K
V = 1327.86 (8) Å^3	Plate, colourless
Z = 4	0.24 × 0.20 × 0.12 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2344 independent reflections
Radiation source: fine-focus sealed tube	1929 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.033
ω and ϕ scans	θmax = 25.0°, θmin = 1.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 2007)	h = −14→14
Tmin = 0.770, Tmax = 1.000	k = −6→6
11209 measured reflections	l = −23→23

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)] = 0.033	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.092	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0489P)^2 + 0.8292P] where P = (Fo^2 + 2Fc^2)/3
2344 reflections	(Δ/σ)max = 0.001
172 parameters	Δρmax = 0.37 e Å^−3
0 restraints	Δρmin = −0.62 e Å^−3

Special details

Experimental. 3-(Bromo acetyl) phenyl benzoate: it was obtained as an off-white solid; M.P: 378k; GCMS data m/e 320 1H NMR (300 MHz, CDCl3, δ, p.p.m.): 4.46 (s 2H, Methylene-CH₂),7.50 (s,1H, Ar—H), 7.52 (s,1H, Ar—H), 7.66 (s,1H, Ar—H), 7.68 (s,1H, Ar—H), 7.88 (s,1H, Ar—H), 7.90 (s,1H, Ar—H), 8.19 (d,2H, Ar—H),

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
Br1	0.93093 (3)	−0.55127 (7)	0.763352 (16)	0.05813 (16)
O1	0.57395 (15)	0.2166 (4)	0.92902 (10)	0.0458 (5)
O2	1.00505 (17)	−0.2020 (5)	0.87494 (14)	0.0697 (7)
O3	0.5845 (2)	0.5101 (5)	0.84970 (16)	0.0724 (8)
C1	0.8494 (2)	−0.3090 (7)	0.81046 (16)	0.0524 (8)
H1A	0.8210	−0.1928	0.7772	0.063*
H1B	0.7893	−0.3891	0.8319	0.063*
C2	0.9115 (2)	−0.1696 (6)	0.86438 (15)	0.0410 (7)
C3	0.8497 (2)	0.0154 (5)	0.90374 (14)	0.0371 (7)
C4	0.7386 (2)	0.0330 (6)	0.89847 (14)	0.0378 (6)
H4	0.7002	−0.0766	0.8710	0.045*
C5	0.6866 (2)	0.2118 (6)	0.93378 (14)	0.0396 (7)
C6	0.7396 (3)	0.3758 (6)	0.97553 (16)	0.0489 (8)
H6	0.7025	0.4965	0.9991	0.059*
C7	0.8502 (3)	0.3567 (7)	0.98166 (16)	0.0519 (8)
H7	0.8878	0.4647	1.0100	0.062*
C8	0.9040 (2)	0.1796 (6)	0.94613 (14)	0.0438 (7)
H8	0.9780	0.1693	0.9505	0.053*
C9	0.5314 (2)	0.3695 (6)	0.88120 (16)	0.0430 (7)
C10	0.4140 (2)	0.3355 (6)	0.87324 (15)	0.0392 (7)
C11	0.3575 (3)	0.5030 (6)	0.83355 (19)	0.0564 (9)
H11	0.3929	0.6327	0.8127	0.068*
C12	0.2485 (3)	0.4773 (7)	0.8249 (2)	0.0626 (10)
H12	0.2102	0.5922	0.7992	0.075*
C13	0.1965 (3)	0.2843 (7)	0.85389 (17)	0.0553 (9)
H13	0.1231	0.2664	0.8473	0.066*
C14	0.2517 (3)	0.1179 (7)	0.89246 (18)	0.0546 (9)
H14	0.2158	−0.0137	0.9120	0.066*
C15	0.3611 (2)	0.1427 (6)	0.90285 (16)	0.0476 (7)
H15	0.3984	0.0294	0.9297	0.057*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.0559 (2)	0.0682 (3)	0.0502 (2)	0.01670 (17)	−0.00215 (15)	−0.00925 (17)
O1	0.0314 (10)	0.0549 (13)	0.0512 (12)	0.0049 (10)	0.0054 (9)	0.0110 (10)
O2	0.0332 (13)	0.0820 (19)	0.0935 (18)	0.0101 (12)	−0.0161 (11)	−0.0277 (15)
O3	0.0443 (13)	0.0693 (17)	0.103 (2)	−0.0134 (12)	−0.0088 (13)	0.0430 (16)
C1	0.0366 (16)	0.069 (2)	0.0517 (17)	0.0138 (16)	−0.0050 (13)	−0.0151 (17)
C2	0.0282 (15)	0.0483 (18)	0.0463 (16)	−0.0014 (13)	−0.0045 (12)	0.0000 (15)
C3	0.0308 (14)	0.0420 (17)	0.0384 (15)	−0.0019 (12)	−0.0043 (12)	0.0032 (12)
C4	0.0319 (14)	0.0423 (16)	0.0391 (15)	−0.0034 (13)	−0.0045 (12)	0.0002 (13)
C5	0.0318 (14)	0.0472 (18)	0.0400 (15)	0.0001 (13)	0.0014 (12)	0.0079 (14)
C6	0.055 (2)	0.0480 (18)	0.0440 (17)	0.0006 (16)	0.0034 (14)	−0.0049 (15)
C7	0.054 (2)	0.055 (2)	0.0466 (17)	−0.0136 (17)	−0.0107 (14)	−0.0067 (16)
C8	0.0349 (15)	0.0523 (19)	0.0440 (16)	−0.0076 (14)	−0.0085 (13)	0.0005 (15)
C9	0.0398 (16)	0.0384 (16)	0.0510 (17)	0.0032 (14)	0.0036 (14)	0.0030 (15)
C10	0.0353 (15)	0.0350 (16)	0.0474 (16)	0.0028 (13)	0.0029 (12)	−0.0009 (14)
C11	0.0446 (18)	0.054 (2)	0.071 (2)	0.0005 (16)	0.0005 (16)	0.0201 (18)
C12	0.049 (2)	0.067 (2)	0.071 (2)	0.0112 (18)	−0.0079 (17)	0.0168 (19)
C13	0.0350 (16)	0.067 (2)	0.064 (2)	0.0000 (16)	−0.0008 (15)	0.0002 (19)
C14	0.0405 (18)	0.054 (2)	0.069 (2)	−0.0080 (16)	0.0076 (15)	0.0077 (18)
C15	0.0416 (17)	0.0445 (18)	0.0568 (18)	0.0030 (15)	0.0028 (14)	0.0060 (16)

Geometric parameters (Å, º)

Br1—C1	1.910 (3)	C7—C8	1.370 (5)
O1—C9	1.353 (4)	C7—H7	0.9300
O1—C5	1.411 (3)	C8—H8	0.9300
O2—C2	1.198 (3)	C9—C10	1.485 (4)
O3—C9	1.191 (4)	C10—C15	1.372 (4)
C1—C2	1.503 (4)	C10—C11	1.384 (4)
C1—H1A	0.9700	C11—C12	1.378 (5)
C1—H1B	0.9700	C11—H11	0.9300
C2—C3	1.489 (4)	C12—C13	1.362 (5)
C3—C8	1.388 (4)	C12—H12	0.9300
C3—C4	1.395 (4)	C13—C14	1.359 (5)
C4—C5	1.363 (4)	C13—H13	0.9300
C4—H4	0.9300	C14—C15	1.387 (4)
C5—C6	1.372 (4)	C14—H14	0.9300
C6—C7	1.390 (4)	C15—H15	0.9300
C6—H6	0.9300
C9—O1—C5	116.0 (2)	C7—C8—C3	121.0 (3)
C2—C1—Br1	114.3 (2)	C7—C8—H8	119.5
C2—C1—H1A	108.7	C3—C8—H8	119.5
Br1—C1—H1A	108.7	O3—C9—O1	122.3 (3)
C2—C1—H1B	108.7	O3—C9—C10	125.8 (3)
Br1—C1—H1B	108.7	O1—C9—C10	111.9 (3)
H1A—C1—H1B	107.6	C15—C10—C11	119.6 (3)
O2—C2—C3	121.6 (3)	C15—C10—C9	122.2 (3)
O2—C2—C1	122.6 (3)	C11—C10—C9	118.2 (3)
C3—C2—C1	115.8 (2)	C12—C11—C10	119.8 (3)
C8—C3—C4	118.5 (3)	C12—C11—H11	120.1
C8—C3—C2	119.3 (3)	C10—C11—H11	120.1
C4—C3—C2	122.2 (3)	C13—C12—C11	120.4 (3)
C5—C4—C3	119.6 (3)	C13—C12—H12	119.8
C5—C4—H4	120.2	C11—C12—H12	119.8
C3—C4—H4	120.2	C14—C13—C12	120.1 (3)
C4—C5—C6	122.4 (3)	C14—C13—H13	120.0
C4—C5—O1	117.6 (3)	C12—C13—H13	120.0
C6—C5—O1	120.0 (3)	C13—C14—C15	120.5 (3)
C5—C6—C7	118.3 (3)	C13—C14—H14	119.7
C5—C6—H6	120.9	C15—C14—H14	119.7
C7—C6—H6	120.9	C10—C15—C14	119.6 (3)
C8—C7—C6	120.3 (3)	C10—C15—H15	120.2
C8—C7—H7	119.8	C14—C15—H15	120.2
C6—C7—H7	119.8
Br1—C1—C2—O2	2.7 (5)	C4—C3—C8—C7	−0.6 (4)
Br1—C1—C2—C3	−178.1 (2)	C2—C3—C8—C7	178.2 (3)
O2—C2—C3—C8	9.9 (5)	C5—O1—C9—O3	−7.3 (5)
C1—C2—C3—C8	−169.3 (3)	C5—O1—C9—C10	171.8 (2)
O2—C2—C3—C4	−171.4 (3)	O3—C9—C10—C15	168.8 (3)
C1—C2—C3—C4	9.4 (4)	O1—C9—C10—C15	−10.3 (4)
C8—C3—C4—C5	1.1 (4)	O3—C9—C10—C11	−10.1 (5)
C2—C3—C4—C5	−177.6 (3)	O1—C9—C10—C11	170.8 (3)
C3—C4—C5—C6	−0.8 (4)	C15—C10—C11—C12	1.0 (5)
C3—C4—C5—O1	−177.6 (2)	C9—C10—C11—C12	179.9 (3)
C9—O1—C5—C4	−95.2 (3)	C10—C11—C12—C13	−1.6 (6)
C9—O1—C5—C6	87.9 (3)	C11—C12—C13—C14	1.1 (6)
C4—C5—C6—C7	−0.1 (5)	C12—C13—C14—C15	0.1 (6)
O1—C5—C6—C7	176.6 (3)	C11—C10—C15—C14	0.2 (5)
C5—C6—C7—C8	0.7 (5)	C9—C10—C15—C14	−178.7 (3)
C6—C7—C8—C3	−0.3 (5)	C13—C14—C15—C10	−0.7 (5)

Hydrogen-bond geometry (Å, º)

Cg2 is the centroid of the C10–C15 benzene ring.

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O3^i	0.93	2.70	3.557 (4)	153
C1—H1B···O3^i	0.97	2.65	3.550 (4)	155
C6—H6···Cg2^ii	0.93	2.88	3.627 (3)	138

Symmetry codes: (i) x, y−1, z; (ii) −x+1, −y+1, −z.