2,8-Dibromo-6H,12H-6,12-epoxydibenzo[b,f][1,5]dioxocine

Abstract

The title dibromodisalicylaldehyde, obtained as a by-product in the m-chloroperoxybenzoic acid oxidation of 5-bromo-2-(methoxymethoxy)benzaldehyde, has been characterised by IR and NMR spectroscopy and X-ray diffraction. The structure features two independent molecules with a π–π stacking interaction between them.

1. Introduction

Ever since salicylaldehyde 1 was first studied in the mid-19th century, it was observed to undergo dehydrative dimerisation, particularly under acidic conditions, to give a compound variously described as “parasalicyl” [1,2] and disalicylaldehyde [3]. There were various suggestions as to its structure and in a definitive paper of 1922 [4] this was finally shown by chemical methods to be the interesting dibenzo-fused trioxabicyclo[3.3.1]nonadiene 2 (Scheme 1). The activity of substituted derivatives of 2 as antimicrobial agents has been reported [5].

In the course of recent synthetic work, we were carrying out a Baeyer–Villiger oxidation of the methoxymethyl-ether-protected 5-bromosalicylaldehyde 3 to give the protected bromocatechol 4 and, in addition to the expected product, obtained a minor by-product in low yield which turned out to be the dibromo derivative of disalicylaldehyde 5 (Scheme 2). This has only been mentioned once before in a 1940 paper where it was obtained by direct bromination of 2 and only a melting point was given [6]. We describe here the full characterisation of this compound including its IR and NMR spectra and X-ray structure determination.

2. Results

The starting compound 3 was prepared according to a literature procedure [7] and subjected to m-chloroperoxybenzoic acid (m-CPBA) oxidation as described in a patent [8]. We faced significant difficulty in separating the desired product 4 from the m-chlorobenzoic acid and even after several washings had to subject the residue to column chromatography. This did give the required product 4 in 75% isolated yield after a further recrystallisation, but a fast-running minor component was also obtained which proved to be the unexpected dibromodisalicylaldehyde 5 (4%). In addition to NMR signals for a 1,2,4-trisubstituted benzene ring (see Supplementary Materials), this had a distinctive singlet at δ_H 6.28 and δ_C 89.4 ppm in agreement with expectation for a benzylic ArCH(OR)₂ environment. The IR spectrum showed no significant signals above 1650 cm^–1 confirming the absence of OH and C=O. The material failed to give any meaningful mass spectrometric data.

Recrystallisation from hexane gave colourless prisms suitable for X-ray diffraction and the resulting structure (Figure 1) shows two independent but closely similar molecules in the unit cell. At 1.888(8)–1.892(8) Å the C–Br distances are rather short compared to the mean value of 1.899 Å for ArC–Br [9]. Two views of the molecule (Figure 2) show that the central trioxabicyclo[3.3.1] ring system is symmetrical and distinctly angular.

As far as we are aware, only six compounds with this core structure have been previously characterised by X-ray diffraction (Figure 3) and the key geometric parameters for these are compared with 5 in

Table 1. Comparison of selected geometric parameters for 5 and related compounds (Å, °).

Compd	Bridging C–O Length (s)	Angle at Bridging O	Angle(s) at Ring Os	Angle between Mean Planes	Ref
5	1.404 (10), 1.410 (11)	109.6 (6)	111.6 (6), 112.4 (7)	72.9	This work
5	1.403 (11), 1.407 (11)	109.9 (6)	112.5 (6), 112.7 (6)	73.5	This work
6 FADVOV	1.418	108.6	112.3 (2)	71.7	[10]
2 ZIZSAC	1.549	106.5	117.9 (9)	65.9	[11]
7 TOLDAC	1.415(2), 1.417(2)	108.0(1)	111.4(1), 111.9(1)	73.5	[12]
8 ZOLBOR	1.411(3), 1.416(3)	107.8(2)	111.5(2), 111.7(2)	72.75	[13]
9 UGIPIJ	1.408(5), 1.414(5)	109.3(3)	112.2(2), 112.3(3)	72.75	[14]
10 UGIPEF	1.413(2), 1.417(2)	111.0(1)	112.6(1), 113.1(1)	73.6	[14]

. It can be seen that these form a relatively consistent pattern with the possible exception of the parent compound 2 which has longer bridging C–O bonds, a larger angle at the ring oxygens and a smaller angle between the mean planes. This last parameter is the angle between the planes defined by the five atoms making up each of the three-atom bridges in the bicyclo[3.3.1] system, i.e., CH–O–C=C–CH.

The other main feature of the crystal structure of 5, which is not evident in Figure 1, is the arrangement of adjacent pairs of independent molecules to allow a favourable π–π stacking interaction between them (Figure 4, distance between two mean planes 3.384 Å, centroid···centroid distance 3.602(6) Å). Among the six other structures of Figure 3 this feature only seems to occur for 2 (distance between two mean planes 3.264 Å). We assume that the presence of bulky substituents in the other cases prevents this arrangement.

In summary, the dibromodisalicylaldehyde 5 obtained as a minor by-product has been spectroscopically characterised for the first time and its X-ray crystal structure consist of pairs of independent molecules in a π–π stacking arrangement.

3. Experimental

Melting points were recorded on a Reichert hot-stage microscope (Reichert, Vienna, Austria) and are uncorrected. IR spectra were recorded using the ATR technique on a Shimadzu IRAffinity 1S instrument. NMR spectra were obtained using a Bruker AV300 instrument (Bruker, Billerica, MA, USA). Spectra were run with internal Me₄Si as the reference and chemical shifts are reported in ppm to high frequency of the reference.

3.1. Reaction Leading to Formation of 5

A solution of 5-bromo-2-methoxymethoxybenzaldehyde 3 [7] (20.0 g, 81.6 mmol) and m-chloroperoxybenzoic acid (28.8 g, 116.7 mmol) in CH₂Cl₂ (300 mL) was stirred at RT for 18 h. The mixture was filtered and the filtrate was stirred with 2 M aqueous Na₂S₂O₃ for 2 h. The organic layer was separated, dried and evaporated to give a solid (25.3 g). Column chromatography of this (SiO₂, hexane/EtOAc, 4:1) gave, as the first fraction, by-product 5 (0.66 g, 4%) followed by the desired product 4 (14.35 g, 75%) which had data in agreement with the published values [8].

Data for 5: mp 157–159 °C (lit. [6] 168 °C); IR: ν_max/cm^–1 1607, 1477, 1412, 1265, 1221, 1184, 1132, 957, 881, 858, 814; ¹H NMR (300 MHz, CDCl₃, 25 °C): δ 6.28 (2H, s, OCHO, H-6,12), 6.79 (2H, d, J 6.6 Hz, H-4,10), 7.36 (2H, dd, J 6.6, 1.8 Hz, H-3,9), 7.42 (2H, d, J 1.8 Hz, H-1,7); ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ 89.4 (2CH, OCHO, C-6,12), 113.9 (2C, C-2,8), 118.6 (2CH, C-4,10), 121.3 (2C, C-6a,12a), 130.1 (2CH, C-1,7), 134.2 (2CH, C-3,9), 149.4 (2C, C-4a,10a). ¹³C NMR assignments for CH confirmed by HSQC. Recrystallisation of 5 from hexane gave crystals suitable for X-ray diffraction.

3.2. X-ray Structure Determination of 5

X-ray diffraction data for compound 5 was collected at 173 K using a Rigaku FR-X Ultrahigh Brilliance Microfocus RA generator/confocal optics with XtaLAB P200 diffractometer [Mo Kα radiation (λ = 0.71073 Å)]. Data were collected and processed (including correction for Lorentz, polarization and absorption) using CrysAlisPro [15]. Structures were solved by dual-space methods (SHELXT) [16] and refined by full-matrix least-squares against F² (SHELXL-2019/3) [17]. Non-hydrogen atoms were refined anisotropically, and hydrogen atoms were refined using a riding model. All calculations were performed using the Olex2 [18] interface.

Crystal data for C₁₄H₈Br₂O₃, M = 384.02 g mol^–1, colourless prism, crystal dimensions 0.09 × 0.08 × 0.06 mm, triclinic, space group P-1 (No. 2), a = 6.9692(3), b = 9.2930(4), c = 21.4788(10) Å, α = 97.000(4), β = 97.013(4), γ = 110.805(4) °, V = 1270.00(10) ų, Z = 4, D_calc = 2.008 g cm^–3, T = 173 K, R₁ = 0.0798, wR₂ = 0.1442 for 4246 reflections with I > 2σ(I), and 343 variables, R_int 0.0422, Goodness of fit on F² 1.323. Data have been deposited at the Cambridge Crystallographic Data Centre as CCDC 2290326. The data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/getstructures.