N-Acetyl-3,5-dibromo-l-tyrosine hemihydrate

Bovonsombat, P.; Snyder, J.; Caruso, F.; Rossi, M.

doi:10.1107/S1600536812032928

organic compounds

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ISSN: 2056-9890

Volume 68| Part 9| September 2012| Pages o2601-o2602

doi:10.1107/S1600536812032928

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N-Acetyl-3,5-dibromo-L-tyrosine hemihydrate

Pakorn Bovonsombat,^a ^* John Snyder,^b Francesco Caruso ^c and Miriam Rossi ^b

^aMahidol University International College, Mahidol University, Salaya Campus, Nakorn Pathom 73170, Thailand, ^bDepartment of Chemistry, Vassar College, Poughkeepsie, NY 12604-0484, USA, and ^cIstituto Chimica Biomolecolare CNR, P.le Aldo Moro 5, 00185, Rome, Italy
^*Correspondence e-mail: icpakorn@mahidol.ac.th

(Received 22 June 2012; accepted 20 July 2012; online 1 August 2012)

The title compound, C₁₁H₁₁Br₂NO₄·0.5H₂O, was prepared by an electrophilic bromination of N-acetyl-L-tyrosine in acetonitrile at room temperature. The two independent molecules do not differ substantially and a molecule of water completes the asymmetric unit. The synthesis of the title compound does not modify the stereochemical center, as shown by the absolute configuration found in this crystal structure. Comparison with the non-bromo starting material differs mainly by rotation features. For instance the H(methine)—C(chiral center)—C(methylene)—C(ipso) is 173.0 (2)° torsion angle in one molecule and 177.3 (2)° in the other, indicating a trans arrangement. This is in contrast with approximately 50° in the starting material. A short intermolecular Br⋯Br separation is observed [3.2938 (3) Å]. The molecules in the crystal are connected via a network of hydrogen bonds through an N—H⋯O hydrogen bond between the hydroxy group of the phenol of the tyrosine and the N—H of the amide of the other molecule and an O—H⋯O hydrogen bond between the hydroxy group of the carboxylic acid and the oxygen of the carbonyl of the amide.

Related literature

N-Acetyl-3,5-dibromo-L-tyrosine is a substrate of biological interest, for instance it is involved in the synthesis of isodityrosine unit, which has been found in numerous biologically active natural products that include K-13, OF4949 and vancomycin family of glycopeptide antibiotics. For the synthesis and specific optical activity of the title compound, see: Bovonsombat et al. (2008 ); Dewitt & Ingersoll (1951 ). For the synthesis of isodityrosine, see: Guo et al. (1997 ). For the structure of Bastadin 6, see: Kazlauskas et al. (1980 , 1981 ). For the structure of the starting material, N-acetyl-L-tyrosine, see: Koszelak & van der Helm (1981 ). For structures with similarly short Br⋯Br contacts, see Quast et al. (1995 ).

Experimental

Crystal data

C₁₁H₁₁Br₂NO₄·0.5H₂O
M_r = 390.02
Monoclinic, P 2₁
a = 7.1095 (3) Å
b = 22.5186 (9) Å
c = 8.6486 (4) Å
β = 105.946 (1)°
V = 1331.3 (1) Å³
Z = 4
Mo Kα radiation
μ = 6.10 mm⁻¹
T = 125 K
0.23 × 0.17 × 0.05 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker 2007 ) T_min = 0.334, T_max = 0.750
18331 measured reflections
7067 independent reflections
6449 reflections with I > 2σ(I)
R_int = 0.030

Refinement

R[F² > 2σ(F²)] = 0.022
wR(F²) = 0.048
S = 0.92
7067 reflections
361 parameters
17 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.34 e Å⁻³
Absolute structure: Flack (1983 ), 3399 Friedel pairs
Flack parameter: 0.005 (5)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2N⋯O1ⁱ	0.85 (1)	2.11 (1)	2.945 (3)	169 (3)
O7—H7O⋯O1Wⁱⁱ	0.83 (1)	1.78 (1)	2.607 (3)	171 (3)
O1W—H1W⋯O4ⁱⁱⁱ	0.84 (1)	2.11 (2)	2.814 (3)	142 (3)
O1W—H2W⋯O2^iv	0.83 (1)	2.01 (1)	2.836 (3)	172 (4)
N1—H1N⋯O5^v	0.85 (1)	2.31 (1)	3.152 (3)	170 (2)
O3—H3O⋯O8^iv	0.83 (1)	1.76 (1)	2.573 (2)	165 (3)
O5—H5O⋯Br4	0.83 (1)	2.73 (3)	3.1096 (16)	110 (2)
O5—H5O⋯O4^vi	0.83 (1)	1.96 (1)	2.732 (2)	156 (3)
O1—H1O⋯O6^vii	0.83 (1)	2.06 (2)	2.750 (2)	141 (3)
O1—H1O⋯Br3	0.83 (1)	2.61 (3)	3.0777 (17)	117 (2)
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+1]$ ; (ii) x-1, y, z; (iii) x+1, y, z; (iv) x, y, z-1; (v) $[-x, y-{\script{1\over 2}}, -z+1]$ ; (vi) $[-x, y+{\script{1\over 2}}, -z+1]$ ; (vii) $[-x+1, y-{\script{1\over 2}}, -z+1]$ .

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536812032928/bg2470sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812032928/bg2470Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812032928/bg2470Isup3.cml

checkCIF report

Comment top

We report here the structure of the title compound (I). The 3,5-dibromo-L-tyrosine moiety is an integral part of Bastadin 6, a secondary metabolite possessing antibacterial activity against Gram-positve bacteria, extracted from Verongrid sponge Ianthella basta. Geometrical parameters of both independent molecules do not differ substantially. Comparison with the non-bromo starting material differs mainly by rotation features. For instance the torsion angle H(methine)-C(chiral center)-C(methylene)-C(ipso) is 173.0 (2)° in one molecule, 177.3 (2)° in the other, indicating a trans arrangement. This is in contrast with 49.5 Å in the starting material (Koszelak & van der Helm, 1981). The intermolecular Br1—Br2 separation of 3.2938 (3) Å is markedly shorter than the corresponding van der Waals Br—Br separation. A similar Br–Br short separation (Br—Br = 3.295 (2) Å)) is found in exo-4,exo-8-dibromo-3,7-bis(phenylsulfonyl)bicyclo(3.3.1)nona-2,6-diene (Quast et al. (1995)). A related exploration in the CSD displays 2948 hits shorter than 3.70?Å. In about 200 hits, related Br—Br separations shorter than 3.30?Å are found, and many of them include isolated Br atoms.

Related literature top

N-Acetyl-3,5-dibromo-L-tyrosine is a substrate of biological interest, for instance it is involved in the synthesis of isodityrosine unit, which has been found in numerous biologically active natural products that include K-13, OF4949 and vancomycin family of glycopeptide antibiotics. For the synthesis and specific optical activity of the title compound, see: Bovonsombat et al. (2008); Dewitt & Ingersoll (1951). For the synthesis of isodityrosine, see: Guo et al. (1997). For the structure of Bastadin 6, see: Kazlauskas et al. (1980, 1981). For the structure of the starting material, N-acetyl-L-tyrosine, see: Koszelak & van der Helm (1981). For structures with similarly short Br···Br contacts, see Quast et al. (1995).

Experimental top

To a stirring solution of N-acetyl-L-tyrosine (1 mmol) in 20 ml of solvent, 2 mmol (2.0 equivalents) of N-bromosuccinimide were added in one portion. The reaction was left to stir at room temperature for 18 h. For the work up, the organic solution was diluted with 80 ml of ethyl acetate and washed three times (20 ml aliquots) with a 5% aqueous solution of Na₂S₂O₃, followed by three washes with water (20 ml aliquots) and lastly with brine. After evaporation of the solvents under vacuum, the solid was subjected to silica gel chromatography (EtOAc/hexanes/CH₃OH (6:3:1) and 0.1% acetic acid). The product was recrystallized from water. NMR data are consistent with those reported in the literature, Bovonsombat et al. (2008). For the crystal structure experiment, the crystals were obtained from a partially dried solution of the title compound dissolved in methanol (10 mg in 2 ml of methanol).

Computing details top

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. Ellipsoid plot.

N-Acetyl-3,5-dibromo-L-tyrosine hemihydrate top

Crystal data top

C₁₁H₁₁Br₂NO₄·0.5H₂O	F(000) = 764
M_r = 390.02	D_x = 1.946 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 9469 reflections
a = 7.1095 (3) Å	θ = 2.5–30.2°
b = 22.5186 (9) Å	µ = 6.10 mm⁻¹
c = 8.6486 (4) Å	T = 125 K
β = 105.946 (1)°	Plate, colourless
V = 1331.3 (1) Å³	0.23 × 0.17 × 0.05 mm
Z = 4

Data collection top

Bruker SMART CCD area-detector diffractometer	7067 independent reflections
Radiation source: fine-focus sealed tube	6449 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.030
phi and ω scans	θ_max = 29.1°, θ_min = 1.8°
Absorption correction: multi-scan (SADABS; Bruker 2007)	h = −9→9
T_min = 0.334, T_max = 0.750	k = −30→30
18331 measured reflections	l = −11→11

Refinement top

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)] = 0.022	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.048	w = 1/[σ²(F_o²)]
S = 0.92	(Δ/σ)_max = 0.003
7067 reflections	Δρ_max = 0.41 e Å⁻³
361 parameters	Δρ_min = −0.34 e Å⁻³
17 restraints	Absolute structure: Flack (1983), 3399 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.005 (5)

Crystal data top

C₁₁H₁₁Br₂NO₄·0.5H₂O	V = 1331.3 (1) Å³
M_r = 390.02	Z = 4
Monoclinic, P2₁	Mo Kα radiation
a = 7.1095 (3) Å	µ = 6.10 mm⁻¹
b = 22.5186 (9) Å	T = 125 K
c = 8.6486 (4) Å	0.23 × 0.17 × 0.05 mm
β = 105.946 (1)°

Data collection top

Bruker SMART CCD area-detector diffractometer	7067 independent reflections
Absorption correction: multi-scan (SADABS; Bruker 2007)	6449 reflections with I > 2σ(I)
T_min = 0.334, T_max = 0.750	R_int = 0.030
18331 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.022	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.048	Δρ_max = 0.41 e Å⁻³
S = 0.92	Δρ_min = −0.34 e Å⁻³
7067 reflections	Absolute structure: Flack (1983), 3399 Friedel pairs
361 parameters	Absolute structure parameter: 0.005 (5)
17 restraints

Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Br1	0.52379 (3)	0.027010 (11)	0.09624 (3)	0.02171 (6)
Br2	−0.20768 (3)	0.529982 (10)	0.26246 (3)	0.02077 (6)
Br3	0.70806 (4)	−0.044388 (11)	0.74402 (3)	0.02526 (7)
Br4	−0.01205 (4)	0.612664 (12)	0.90382 (3)	0.02911 (7)
C1	0.6076 (3)	0.00179 (10)	0.4288 (3)	0.0144 (4)
C2	0.6679 (3)	0.01750 (11)	0.5896 (3)	0.0170 (5)
C3	0.7095 (3)	0.07588 (11)	0.6382 (3)	0.0181 (5)
H3	0.7475	0.0850	0.7473	0.022*
C4	0.6948 (3)	0.12065 (11)	0.5257 (3)	0.0160 (4)
C5	0.6346 (3)	0.10533 (11)	0.3629 (3)	0.0176 (5)
H5	0.6229	0.1346	0.2850	0.021*
C7	0.7528 (3)	0.18382 (10)	0.5762 (3)	0.0186 (5)
H7B	0.8205	0.2003	0.5028	0.022*
H7A	0.8446	0.1831	0.6824	0.022*
C8	0.5815 (3)	0.22554 (10)	0.5802 (3)	0.0168 (5)
H8	0.6378	0.2634	0.6268	0.020*
C9	0.5205 (4)	0.20950 (11)	0.8411 (3)	0.0217 (5)
C10	0.3882 (4)	0.18128 (12)	0.9301 (3)	0.0320 (7)
H10C	0.2806	0.1622	0.8546	0.048*
H10A	0.3392	0.2113	0.9876	0.048*
H10B	0.4606	0.1524	1.0047	0.048*
C12	−0.1141 (3)	0.56247 (11)	0.5916 (3)	0.0168 (5)
C13	−0.0614 (3)	0.54956 (12)	0.7546 (3)	0.0202 (5)
C17	−0.1403 (3)	0.51408 (11)	0.4856 (3)	0.0163 (5)
C16	−0.1215 (3)	0.45657 (12)	0.5400 (3)	0.0184 (5)
H16	−0.1406	0.4256	0.4661	0.022*
C14	−0.0419 (3)	0.49135 (12)	0.8107 (3)	0.0202 (5)
H14	−0.0068	0.4843	0.9209	0.024*
C11	0.4499 (3)	0.23828 (10)	0.4122 (3)	0.0156 (5)
C15	−0.0741 (3)	0.44352 (11)	0.7047 (3)	0.0179 (5)
C20	0.1074 (4)	0.33012 (10)	0.5784 (3)	0.0199 (5)
C19	0.1059 (3)	0.34237 (10)	0.7516 (3)	0.0195 (5)
H19	0.0927	0.3038	0.8002	0.023*
C21	0.3886 (3)	0.34854 (10)	0.9878 (3)	0.0169 (5)
C22	0.5904 (4)	0.37301 (11)	1.0570 (3)	0.0205 (5)
H22C	0.6055	0.4087	1.0009	0.031*
H22B	0.6853	0.3443	1.0454	0.031*
H22A	0.6097	0.3817	1.1689	0.031*
C18	−0.0683 (4)	0.38071 (11)	0.7657 (3)	0.0224 (5)
H18B	−0.1881	0.3610	0.7075	0.027*
H18A	−0.0672	0.3821	0.8781	0.027*
C6	0.5923 (3)	0.04698 (11)	0.3168 (3)	0.0161 (5)
N1	0.4654 (3)	0.20206 (9)	0.6814 (2)	0.0177 (4)
H1N	0.371 (3)	0.1796 (10)	0.634 (3)	0.021*
N2	0.2930 (3)	0.36671 (9)	0.8409 (2)	0.0189 (4)
H2N	0.334 (4)	0.3930 (9)	0.788 (3)	0.023*
O1	0.5651 (2)	−0.05488 (7)	0.3754 (2)	0.0185 (4)
H1O	0.611 (4)	−0.0801 (9)	0.445 (2)	0.022*
O2	0.6678 (3)	0.23827 (9)	0.9097 (2)	0.0316 (4)
O3	0.5303 (3)	0.27618 (9)	0.3358 (2)	0.0269 (4)
H3O	0.446 (3)	0.2834 (13)	0.2502 (19)	0.032*
O4	0.2913 (2)	0.21517 (7)	0.35608 (19)	0.0187 (3)
O5	−0.1397 (2)	0.61836 (8)	0.53021 (19)	0.0206 (4)
H5O	−0.166 (4)	0.6438 (9)	0.590 (3)	0.025*
O6	0.2455 (3)	0.33961 (8)	0.5251 (2)	0.0257 (4)
O7	−0.0617 (3)	0.30763 (9)	0.4961 (2)	0.0284 (4)
H7O	−0.051 (4)	0.2962 (13)	0.4076 (19)	0.034*
O8	0.3140 (2)	0.31234 (8)	1.0623 (2)	0.0234 (4)
O1W	0.9302 (3)	0.26971 (13)	0.2095 (3)	0.0520 (7)
H1W	1.038 (3)	0.2551 (16)	0.207 (4)	0.062*
H2W	0.847 (4)	0.2589 (17)	0.127 (3)	0.062*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.02863 (13)	0.02049 (12)	0.01247 (12)	0.00333 (11)	−0.00033 (10)	−0.00168 (10)
Br2	0.02392 (13)	0.02328 (14)	0.01258 (12)	0.00015 (11)	0.00074 (10)	0.00066 (10)
Br3	0.03634 (16)	0.02193 (14)	0.01756 (13)	−0.00037 (11)	0.00752 (11)	0.00566 (10)
Br4	0.04323 (17)	0.02575 (14)	0.01522 (13)	0.01038 (12)	0.00278 (11)	−0.00298 (10)
C1	0.0122 (10)	0.0121 (11)	0.0188 (11)	0.0018 (9)	0.0038 (9)	−0.0018 (9)
C2	0.0181 (11)	0.0186 (13)	0.0149 (10)	0.0020 (9)	0.0054 (9)	0.0034 (9)
C3	0.0175 (11)	0.0231 (13)	0.0131 (11)	0.0023 (10)	0.0029 (9)	−0.0034 (9)
C4	0.0124 (10)	0.0150 (11)	0.0197 (11)	0.0008 (9)	0.0027 (9)	−0.0009 (9)
C5	0.0165 (11)	0.0185 (12)	0.0167 (11)	0.0022 (9)	0.0027 (9)	0.0045 (9)
C7	0.0151 (11)	0.0160 (11)	0.0217 (12)	−0.0017 (9)	−0.0002 (9)	0.0001 (9)
C8	0.0202 (11)	0.0128 (11)	0.0148 (11)	−0.0025 (9)	0.0006 (9)	−0.0012 (8)
C9	0.0361 (15)	0.0121 (11)	0.0131 (11)	0.0057 (10)	0.0004 (10)	−0.0008 (9)
C10	0.059 (2)	0.0202 (14)	0.0182 (13)	−0.0014 (13)	0.0134 (13)	0.0011 (11)
C12	0.0135 (11)	0.0204 (13)	0.0163 (12)	0.0031 (9)	0.0039 (9)	0.0021 (10)
C13	0.0166 (12)	0.0259 (13)	0.0174 (12)	0.0025 (10)	0.0033 (10)	−0.0054 (10)
C17	0.0133 (10)	0.0229 (14)	0.0111 (10)	0.0001 (9)	0.0006 (8)	−0.0010 (9)
C16	0.0143 (11)	0.0225 (12)	0.0167 (11)	−0.0016 (10)	0.0015 (9)	−0.0029 (10)
C14	0.0178 (11)	0.0289 (14)	0.0127 (11)	0.0020 (10)	0.0020 (9)	0.0031 (10)
C11	0.0188 (12)	0.0109 (10)	0.0171 (11)	0.0014 (9)	0.0046 (9)	−0.0015 (9)
C15	0.0123 (10)	0.0222 (13)	0.0181 (11)	0.0014 (9)	0.0024 (9)	0.0055 (9)
C20	0.0236 (13)	0.0103 (11)	0.0202 (12)	0.0010 (9)	−0.0031 (10)	0.0023 (9)
C19	0.0230 (12)	0.0146 (11)	0.0176 (12)	−0.0054 (9)	0.0000 (10)	0.0043 (9)
C21	0.0220 (12)	0.0115 (11)	0.0163 (11)	0.0044 (9)	0.0039 (9)	−0.0015 (9)
C22	0.0220 (12)	0.0194 (13)	0.0174 (11)	0.0022 (10)	0.0007 (9)	0.0013 (10)
C18	0.0221 (12)	0.0233 (13)	0.0210 (12)	−0.0035 (10)	0.0046 (10)	0.0047 (10)
C6	0.0158 (11)	0.0209 (12)	0.0099 (11)	0.0023 (9)	0.0010 (9)	−0.0034 (9)
N1	0.0236 (11)	0.0166 (10)	0.0116 (9)	−0.0030 (8)	0.0024 (8)	−0.0016 (8)
N2	0.0218 (10)	0.0149 (10)	0.0169 (10)	−0.0059 (8)	0.0002 (8)	0.0027 (8)
O1	0.0217 (9)	0.0142 (9)	0.0180 (9)	0.0010 (7)	0.0026 (7)	0.0005 (7)
O2	0.0394 (12)	0.0297 (11)	0.0183 (9)	−0.0018 (9)	−0.0047 (8)	−0.0065 (8)
O3	0.0218 (9)	0.0353 (11)	0.0198 (9)	−0.0082 (8)	−0.0008 (7)	0.0117 (8)
O4	0.0178 (8)	0.0163 (8)	0.0192 (8)	−0.0024 (7)	0.0007 (7)	0.0020 (7)
O5	0.0273 (9)	0.0184 (9)	0.0156 (9)	0.0072 (8)	0.0050 (7)	0.0001 (7)
O6	0.0281 (10)	0.0221 (10)	0.0257 (10)	−0.0043 (8)	0.0053 (8)	−0.0087 (8)
O7	0.0292 (10)	0.0302 (11)	0.0203 (9)	−0.0120 (8)	−0.0024 (8)	−0.0030 (8)
O8	0.0240 (9)	0.0275 (10)	0.0171 (8)	−0.0023 (7)	0.0032 (7)	0.0057 (7)
O1W	0.0294 (12)	0.0756 (18)	0.0375 (13)	0.0269 (12)	−0.0135 (10)	−0.0321 (12)

Geometric parameters (Å, º) top

Br1—C6	1.889 (2)	C17—C16	1.372 (4)
Br2—C17	1.890 (2)	C16—C15	1.402 (3)
Br3—C2	1.897 (2)	C16—H16	0.9300
Br4—C13	1.887 (3)	C14—C15	1.392 (4)
C1—O1	1.362 (3)	C14—H14	0.9300
C1—C2	1.384 (3)	C11—O4	1.215 (3)
C1—C6	1.388 (3)	C11—O3	1.304 (3)
C2—C3	1.387 (3)	C15—C18	1.506 (3)
C3—C4	1.385 (3)	C20—O6	1.213 (3)
C3—H3	0.9300	C20—O7	1.318 (3)
C4—C5	1.398 (3)	C20—C19	1.526 (3)
C4—C7	1.512 (3)	C19—N2	1.450 (3)
C5—C6	1.382 (3)	C19—C18	1.542 (3)
C5—H5	0.9300	C19—H19	0.9800
C7—C8	1.546 (3)	C21—O8	1.245 (3)
C7—H7B	0.9700	C21—N2	1.330 (3)
C7—H7A	0.9700	C21—C22	1.499 (3)
C8—N1	1.457 (3)	C22—H22C	0.9600
C8—C11	1.524 (3)	C22—H22B	0.9600
C8—H8	0.9800	C22—H22A	0.9600
C9—O2	1.236 (3)	C18—H18B	0.9700
C9—N1	1.339 (3)	C18—H18A	0.9700
C9—C10	1.510 (4)	N1—H1N	0.852 (7)
C10—H10C	0.9600	N2—H2N	0.847 (7)
C10—H10A	0.9600	O1—H1O	0.829 (7)
C10—H10B	0.9600	O3—H3O	0.832 (7)
C12—O5	1.359 (3)	O5—H5O	0.825 (7)
C12—C13	1.386 (3)	O7—H7O	0.830 (7)
C12—C17	1.403 (3)	O1W—H1W	0.837 (7)
C13—C14	1.391 (4)	O1W—H2W	0.830 (7)

O1—C1—C2	124.0 (2)	C15—C14—C13	121.1 (2)
O1—C1—C6	118.8 (2)	C15—C14—H14	119.5
C2—C1—C6	117.2 (2)	C13—C14—H14	119.5
C1—C2—C3	121.9 (2)	O4—C11—O3	124.4 (2)
C1—C2—Br3	117.70 (18)	O4—C11—C8	124.0 (2)
C3—C2—Br3	120.31 (17)	O3—C11—C8	111.53 (19)
C4—C3—C2	120.5 (2)	C14—C15—C16	117.2 (2)
C4—C3—H3	119.7	C14—C15—C18	120.8 (2)
C2—C3—H3	119.7	C16—C15—C18	121.9 (2)
C3—C4—C5	118.1 (2)	O6—C20—O7	125.2 (2)
C3—C4—C7	121.3 (2)	O6—C20—C19	124.4 (2)
C5—C4—C7	120.5 (2)	O7—C20—C19	110.4 (2)
C6—C5—C4	120.5 (2)	N2—C19—C20	109.8 (2)
C6—C5—H5	119.8	N2—C19—C18	112.7 (2)
C4—C5—H5	119.8	C20—C19—C18	113.7 (2)
C4—C7—C8	115.08 (18)	N2—C19—H19	106.8
C4—C7—H7B	108.5	C20—C19—H19	106.8
C8—C7—H7B	108.5	C18—C19—H19	106.8
C4—C7—H7A	108.5	O8—C21—N2	121.2 (2)
C8—C7—H7A	108.5	O8—C21—C22	122.1 (2)
H7B—C7—H7A	107.5	N2—C21—C22	116.8 (2)
N1—C8—C11	109.89 (18)	C21—C22—H22C	109.5
N1—C8—C7	111.89 (19)	C21—C22—H22B	109.5
C11—C8—C7	111.97 (19)	H22C—C22—H22B	109.5
N1—C8—H8	107.6	C21—C22—H22A	109.5
C11—C8—H8	107.6	H22C—C22—H22A	109.5
C7—C8—H8	107.6	H22B—C22—H22A	109.5
O2—C9—N1	122.0 (2)	C15—C18—C19	116.3 (2)
O2—C9—C10	122.7 (2)	C15—C18—H18B	108.2
N1—C9—C10	115.3 (2)	C19—C18—H18B	108.2
C9—C10—H10C	109.5	C15—C18—H18A	108.2
C9—C10—H10A	109.5	C19—C18—H18A	108.2
H10C—C10—H10A	109.5	H18B—C18—H18A	107.4
C9—C10—H10B	109.5	C5—C6—C1	121.8 (2)
H10C—C10—H10B	109.5	C5—C6—Br1	119.52 (19)
H10A—C10—H10B	109.5	C1—C6—Br1	118.63 (18)
O5—C12—C13	124.2 (2)	C9—N1—C8	121.4 (2)
O5—C12—C17	119.0 (2)	C9—N1—H1N	122.9 (18)
C13—C12—C17	116.9 (2)	C8—N1—H1N	115.2 (18)
C12—C13—C14	121.7 (2)	C21—N2—C19	123.1 (2)
C12—C13—Br4	119.0 (2)	C21—N2—H2N	124.7 (19)
C14—C13—Br4	119.26 (18)	C19—N2—H2N	112.2 (19)
C16—C17—C12	121.7 (2)	C1—O1—H1O	113 (2)
C16—C17—Br2	120.17 (18)	C11—O3—H3O	106 (2)
C12—C17—Br2	118.09 (18)	C12—O5—H5O	115 (2)
C17—C16—C15	121.3 (2)	C20—O7—H7O	108 (2)
C17—C16—H16	119.3	H1W—O1W—H2W	108 (4)
C15—C16—H16	119.3

O1—C1—C2—C3	−179.9 (2)	N1—C8—C11—O3	159.0 (2)
C6—C1—C2—C3	0.7 (3)	C7—C8—C11—O3	−76.0 (2)
O1—C1—C2—Br3	3.8 (3)	C13—C14—C15—C16	1.7 (3)
C6—C1—C2—Br3	−175.51 (16)	C13—C14—C15—C18	−175.2 (2)
C1—C2—C3—C4	−1.1 (3)	C17—C16—C15—C14	−1.7 (3)
Br3—C2—C3—C4	175.04 (17)	C17—C16—C15—C18	175.2 (2)
C2—C3—C4—C5	0.9 (3)	O6—C20—C19—N2	−0.1 (3)
C2—C3—C4—C7	−175.7 (2)	O7—C20—C19—N2	179.62 (19)
C3—C4—C5—C6	−0.3 (3)	O6—C20—C19—C18	127.2 (3)
C7—C4—C5—C6	176.3 (2)	O7—C20—C19—C18	−53.2 (3)
C3—C4—C7—C8	−98.5 (3)	C14—C15—C18—C19	−110.4 (3)
C5—C4—C7—C8	85.1 (3)	C16—C15—C18—C19	72.9 (3)
C4—C7—C8—N1	55.1 (3)	N2—C19—C18—C15	60.6 (3)
C4—C7—C8—C11	−68.8 (3)	C20—C19—C18—C15	−65.1 (3)
O5—C12—C13—C14	178.4 (2)	C4—C5—C6—C1	0.0 (3)
C17—C12—C13—C14	−2.2 (3)	C4—C5—C6—Br1	−176.88 (17)
O5—C12—C13—Br4	−2.3 (3)	O1—C1—C6—C5	−179.5 (2)
C17—C12—C13—Br4	177.10 (17)	C2—C1—C6—C5	−0.2 (3)
O5—C12—C17—C16	−178.3 (2)	O1—C1—C6—Br1	−2.6 (3)
C13—C12—C17—C16	2.3 (3)	C2—C1—C6—Br1	176.72 (16)
O5—C12—C17—Br2	0.6 (3)	O2—C9—N1—C8	2.6 (4)
C13—C12—C17—Br2	−178.86 (17)	C10—C9—N1—C8	−178.4 (2)
C12—C17—C16—C15	−0.3 (3)	C11—C8—N1—C9	−152.5 (2)
Br2—C17—C16—C15	−179.19 (17)	C7—C8—N1—C9	82.5 (3)
C12—C13—C14—C15	0.3 (4)	O8—C21—N2—C19	−5.7 (4)
Br4—C13—C14—C15	−179.05 (17)	C22—C21—N2—C19	173.3 (2)
N1—C8—C11—O4	−22.1 (3)	C20—C19—N2—C21	−135.0 (2)
C7—C8—C11—O4	102.9 (3)	C18—C19—N2—C21	97.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O1ⁱ	0.85 (1)	2.11 (1)	2.945 (3)	169 (3)
O7—H7O···O1Wⁱⁱ	0.83 (1)	1.78 (1)	2.607 (3)	171 (3)
O1W—H1W···O4ⁱⁱⁱ	0.84 (1)	2.11 (2)	2.814 (3)	142 (3)
O1W—H2W···O2^iv	0.83 (1)	2.01 (1)	2.836 (3)	172 (4)
N1—H1N···O5^v	0.85 (1)	2.31 (1)	3.152 (3)	170 (2)
O3—H3O···O8^iv	0.83 (1)	1.76 (1)	2.573 (2)	165 (3)
O5—H5O···Br4	0.83 (1)	2.73 (3)	3.1096 (16)	110 (2)
O5—H5O···O4^vi	0.83 (1)	1.96 (1)	2.732 (2)	156 (3)
O1—H1O···O6^vii	0.83 (1)	2.06 (2)	2.750 (2)	141 (3)
O1—H1O···Br3	0.83 (1)	2.61 (3)	3.0777 (17)	117 (2)

Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) x−1, y, z; (iii) x+1, y, z; (iv) x, y, z−1; (v) −x, y−1/2, −z+1; (vi) −x, y+1/2, −z+1; (vii) −x+1, y−1/2, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₁H₁₁Br₂NO₄·0.5H₂O
M_r	390.02
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	125
a, b, c (Å)	7.1095 (3), 22.5186 (9), 8.6486 (4)
β (°)	105.946 (1)
V (Å³)	1331.3 (1)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	6.10
Crystal size (mm)	0.23 × 0.17 × 0.05

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker 2007)
T_min, T_max	0.334, 0.750
No. of measured, independent and observed [I > 2σ(I)] reflections	18331, 7067, 6449
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.685

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.022, 0.048, 0.92
No. of reflections	7067
No. of parameters	361
No. of restraints	17
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.41, −0.34
Absolute structure	Flack (1983), 3399 Friedel pairs
Absolute structure parameter	0.005 (5)

Computer programs: SMART (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O1ⁱ	0.847 (7)	2.109 (9)	2.945 (3)	169 (3)
O7—H7O···O1Wⁱⁱ	0.830 (7)	1.784 (9)	2.607 (3)	171 (3)
O1W—H1W···O4ⁱⁱⁱ	0.837 (7)	2.11 (2)	2.814 (3)	142 (3)
O1W—H2W···O2^iv	0.830 (7)	2.011 (9)	2.836 (3)	172 (4)
N1—H1N···O5^v	0.852 (7)	2.308 (9)	3.152 (3)	170 (2)
O3—H3O···O8^iv	0.832 (7)	1.762 (11)	2.573 (2)	165 (3)
O5—H5O···Br4	0.825 (7)	2.73 (3)	3.1096 (16)	110 (2)
O5—H5O···O4^vi	0.825 (7)	1.956 (14)	2.732 (2)	156 (3)
O1—H1O···O6^vii	0.829 (7)	2.057 (18)	2.750 (2)	141 (3)
O1—H1O···Br3	0.829 (7)	2.61 (3)	3.0777 (17)	117 (2)

Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) x−1, y, z; (iii) x+1, y, z; (iv) x, y, z−1; (v) −x, y−1/2, −z+1; (vi) −x, y+1/2, −z+1; (vii) −x+1, y−1/2, −z+1.

Acknowledgements

MR thanks the US National Science Foundation, through grant 0521237, for the X-ray diffractometer.

References

Bovonsombat, P., Khanthapura, P., Krause, M. M. & Leykajarakul, J. (2008). Tetrahedron Lett. 49, 7008–7011. Web of Science CrossRef CAS Google Scholar
Bruker (2007). APEX2, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dewitt, H. D. & Ingersoll, A. W. (1951). J. Am. Chem. Soc. 73, 5782–5783. CrossRef CAS Web of Science Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Guo, Z. W., Salamonczyk, G. M., Han, K., Machiya, K. & Sih, C. J. (1997). J. Org. Chem. 62, 6700–6701. CrossRef CAS Web of Science Google Scholar
Kazlauskas, R., Lidgard, R. O., Murphy, P. T. & Well, R. J. (1980). Tetrahedron Lett. 23, 2277–2281. CrossRef Web of Science Google Scholar
Kazlauskas, R., Lidgard, R. O., Murphy, P. T., Well, R. J. & Blount, J. F. (1981). Aust. J. Chem. 34, 765–786. CSD CrossRef CAS Google Scholar
Koszelak, S. N. & van der Helm, D. (1981). Acta Cryst. B37, 1122–1124. CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
Quast, H., Witzel, M., Peters, E. M., Peters, K. & von Schnering, H. G. (1995). Liebigs Ann. pp. 725–738. CrossRef Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122. Web of Science CrossRef CAS IUCr Journals Google Scholar