An efficient synthesis of Rubin's aldehyde and its precursor 1,3,5-Tribromo-2,4,6-tris(dichloromethyl)benzene

Article abstract of DOI:10.1515/znb-2011-0911

2,4,6-Tribromobenzene-1,3,5-tricarboxaldehyde (4) can be efficiently prepared in two reaction steps from 1,3,5-tribromobenzene. The intermediate 1,3,5-tribromo-2,4,6-tris(dichloromethyl)benzene (3) crystallizes from petroleum ether in its C_3h s

Full text of DOI:10.1515/znb-2011-0911

An Efficient Synthesis of Rubin’s Aldehyde and its Precursor
1,3,5-Tribromo-2,4,6-tris(dichloromethyl)benzene
Christoph Holst, Dieter Schollmeyer, and Herbert Meier
Institute of Organic Chemistry, University of Mainz, Duesbergweg 10 – 14, 55099 Mainz, Germany
Reprint requests to Prof. Dr. H. Meier. Fax: +49 (0)6131-3925396.
E-mail: hmeier@mail.uni-mainz.de
Z. Naturforsch. 2011, 66b, 935 – 938; received April 29, 2011
2,4,6-Tribromobenzene-1,3,5-tricarboxaldehyde (4) can be efficiently prepared in two reaction
steps from 1,3,5-tribromobenzene. The intermediate 1,3,5-tribromo-2,4,6-tris(dichloromethyl)benz-
ene (3) crystallizes from petroleum ether in its C3h structure. However, in CDCl3 solution it exists at
room temperature in two isomeric forms: 3a (C3h) and 3b (Cs) (1 : 1.15). The intramolecular Br···Cl
distances are much smaller than the sum of the van der Waals radii. Therefore, the exocyclic C–C
bonds show a hindered rotation.
Key words: Polyfunctional Aromatics, Hexasubstituted Benzenes, Hindered Rotation
Introduction
Benzene derivatives 1 with three functional groups
A1 in 1,3,5-position and three other functional groups
A2 in 2,4,6-position are very valuable starting com-
pounds for orthogonal synthetic strategies. A great
variety of hexasubstituted benzene derivatives can be
prepared on the basis of compounds 1 with different
functionalities.
Rubin’s aldehyde [1, 2], namely 2,4,6-tribromo-
benzene-1,3,5-tricarboxaldehyde
(2,4,6-tribromo-
trimesinaldehyde, A1 = CHO, A2 = Br) served for
example as a precursor of hexaethynylbenzenes and
other [6]star compounds [1 – 3], polycyclic aromatics
[2], fullerene C60 [3], graphyne [3], and polycentric
metal complexes [4]. We are interested in Rubin’s
aldehyde as a precursor of conjugated star-shaped or
dendritic oligomers [5, 6].
Scheme 1. Preparation of Rubin’s aldehyde (4).
veals that we succeeded to prepare 4 in two steps
from commercially available 1,3,5-tribromobenzene
(2). The Friedel-Crafts alkylation of 2 with chloro-
form yielded 1,3,5-tribromo-2,4,6-tris(dichlorometh-
yl)benzene (3) in a yield of 55%. Subsequent hydrol-
ysis of 3 with conc. H2SO4 in the presence of FeSO4
afforded the trialdehyde 4 in 72 % yield (Scheme 1).
1
Table 1 contains the H and 13C NMR data of 3
and 4. In contrast to 4, compound 3 consists in
CDCl3 solution at room temperature of two isomers,
namely 3a, showing C3h symmetry, and the less sym-
metrical rotamer 3b (Cs). Obviously, the rotation of the
dichloromethyl groups is hindered by the neighboring
Br substituents. The statistical ratio 3a : 3b amounts
Results and Discussion
◦
Rubin’s aldehyde (4) is usually obtained from
mesitylene in five reaction steps [1, 2]. Scheme 1 re-
to 1 : 3, the measured ratio (CDCl3, T = −15 C) is
1 : 1.15.
c
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936
C. Holst et al. · Rubin’s Aldehyde and its Precursor 1,3,5-Tribromo-2,4,6-tris(dichloromethyl)benzene
Fig. 1. 1H NMR spec-
tra of
3 in C2D2Cl4:
a) measurement at 365 K,
b) measurement at 260 K,
c) coalescence measure-
ment in the aromatic re-
gion (δ values related
to TMS as internal stan-
dard).
Semiempirical calculations (PC Model V 7.00, fore the free activation energy ∆G= for the exchange
MestRe-C2.3) gave a small enthalpy difference of process can be estimated according to Eq. 1:
0.3 kcal mol−1 in favor of 3a. The statistical entropy
term R ln3 reverts the rotamer distribution.
ꢀ
ꢁ
3TC
∆G= = RTc 22.96 + ln
(1)
3ν2 − (ν1 + ν3 + ν4)
Fig. 1 shows the 1H NMR spectra of 3a, b at 365 K
(85 ◦C) and 260 K (−13 ◦C) in C2D2Cl4 and the corre- At the coalescence temperature Tc = 340 5 K,
sponding coalescence phenomenon in the temperature- the free activation energy ∆G= amounts to 16.7
dependent measurements. Three signals of 3b with the 0.3 kcal mol−1 [7]. This result agrees very well with
frequencies ν1, ν3 and ν4 and one signal of 3a with the the barrier of 16.3 0.4 kcal mol−1 which was ob-
frequency ν2 are involved in the coalescence. There- tained for 1,3,5-trichloro-2,4,6-tris(dichloromethyl)-
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C. Holst et al. · Rubin’s Aldehyde and its Precursor 1,3,5-Tribromo-2,4,6-tris(dichloromethyl)benzene
937
Fig. 2. Part of the crys-
tal structure of 3a which
contains three slightly
different molecules in the
asymmetric unit.
˚
Table 1. 1H and 13C NMR data of 3a and 3b measured in
Table 2. Distances d (A) of the Br atoms from the mean plane
of the benzene ring and distances between the Br and the
Cl atoms of 3aa.
CDCl3 at 20 ◦C.
3a
1H
3b
Distances Br···Cl
Molecule A Molecule B
Molecule C
13C
13C
1H
d (Br-1)
−0.03(1)
3.308(2)
3.317(3)
−0.09(1)
3.342(2)
3.306(2)
0.17(1)
−0.09(1)
3.345(3)
3.345(3)
0.11(2)
3.443(4)
3.460(4)
0.01 (1)
3.501(3)
3.473(6)
−0.05(3)
3.249(3)
3.359(3)
−0.12(1)
3.346(3)
3.345(3)
0.14(1)
C-1
C-2
C-3
C-4
C-5
C-6
127.0
138.3
127.0
138.3
127.0
138.3
125.3
135.9
129.8
140.2
127.4
130.0
Br-1···Cl-3
Br-1···Cl-4
d (Br-2)
Br-2···Cl-5
Br-2···Cl-6
d (Br-3)
2-CHCl2, 6-CHCl2
4-CHCl2
71.1 7.94
71.1 7.94
71.7, 71.8 7.77, 7.78
71.0 7.95
Br-3···Cl-1
3.296(3)
3.346(3)
3.309(3)
3.324(2)
Br-3···Cl-2
a
The crystallographic atom numbering chosen does not correspond
to the IUPAC nomenclature.
benzene [8]. Trialdehyde 4 has a much lower barrier
for the rotation of the formyl groups. Thus, it gives at
room temperature only one set of 1H and 13C signals,
each.
The rotation around the exocyclic C–C single bonds is
considerably hindered, since its transition state has an
even shorter Br···Cl distance.
Crystallization of◦ 3 from a solution in petroleum
ether (b. p. 40 – 70 C) yielded selectively the more
symmetric form 3a (Fig. 2). The asymmetric unit con-
tains three slightly different molecules 3a (A, B, C).
The most interesting geometrical parameters concern
the distances between the Br atoms and the neighbor-
ing Cl atoms of the prochiral CHCl2 groups. The de-
viation of the Br atoms from the plane of the benzene
ring is very small (Table 2). The geminal Cl atoms are
below and above the benzene ring plane in an equiva-
lent distance.
Experimental Section
1H and 13C NMR spectra were recorded on a Bruker
AM 400 spectrometer. Field-desorption MS measurements
were performed with a Finnigan MAT 95 spectrometer. A
Perkin Elmer Spectrum 6X was used for recording the IR
spectra. Elemental analyses were performed in the microan-
alytical laboratory of the Chemistry Department of the Uni-
versity of Mainz.
1,3,5-Tribromo-2,4,6-tris(dichloromethyl)benzene (3a)
1,3,5-Tribromobenzene (2) (1.00 g, 3.18 mmol), AlCl3
The sum of the van der Waals radii of Br and Cl
˚
amounts to 1.80+ 1.95 = 3.75 A. Table 2 reveals that
the distances Br···Cl in 3a are generally much smaller. (0.50 g, 3.75 mmol) and 10 mL of dry CHCl3 were
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938
C. Holst et al. · Rubin’s Aldehyde and its Precursor 1,3,5-Tribromo-2,4,6-tris(dichloromethyl)benzene
which melted at 205 – 206 ◦C. – IR (KBr): ν (cm−1) =
3037, 1516, 1362, 1257, 1222, 990, 784, 704. – FD MS:
m/z (%) = 568/566/564/562/560 (30/81/100/85/44) [M]+
(Br2Cl6 isotope pattern). – C9H3Br3Cl6 (563.56): calcd.
C 19.18, H 0.54; found C 19.10, H 0.71.
Table 3. Details of the X-ray crystal structure analysis of 3a.
Formula
Mr
C9H3Br3Cl6
563.54
Crystal size, mm3
Crystal habit
Crystal system
Space group
0.1×0.2×0.3
block
hexagonal
P65
16.4172(3)
30.2406(6)
7058.6(4)
18
2,4,6-Tribromobenzene-1,3,5-tricarboxaldehyde (4)
˚
a, A
˚
c, A
To Fe2SO4 ·7H2O (20 mg, 0.072 mmol) in 5 mL of conc.
H2SO4 500 mg (0.887 mmol) of 3 was added. The mixture
3
˚
V, A
Z
◦
was vigorously stirred and heated to 130 C. The evolved
T, K
173
2.39
HCl gas was piped into 2 M aqueous NaOH. After 4 h the
Dcalcd, Mg m−3
◦
mixture was cooled to 0 C and treated with 20 mL of ice
F(000), e
4752
8.7
µ(MoKα ), mm−1
Abs. corr.; Tmin / Tmax
hkl range
water. The formed precipitate was washed with H2O (2 ×
30 mL) and purified by flash chromatography (7×7 cm SiO2,
CH2Cl2). Recrystallization form methanol yielded 255 mg
multiscan; 0.07 / 0.15
−20/21, 21, 39
1.4 – 27.8
99752 / 11214 / 0.0843
6859
487 / 1
0.0481 / 0.1225
0.068
θ range, deg
◦
(72 %) of a colorless powder, m. p. 250 C (decomp.). – IR
Refl. measd. / unique / Rint
Refl. with I ≥ 2σ(I)
Param. refined / restraints
R(F) / wR(F2)a [I ≥ 2σ(I)]
Weighting scheme Ab
GoF (F2)c
(KBr): ν (cm−1) = 3392, 2894, 1702, 1537, 1401, 1335, 993,
945. – FD MS: m/z (%) = 402//400/398/396 (35/89/100/25)
[M]+ (Br3 isotope pattern). – C9H3Br3O3 (398.84): calcd.
C 27.10, H 0.76; found C 26.88, H 0.93.
0.889
x(Flack)
∆ρfin (max / min), e A
0.010(9)
2.56 / −1.22
2
Crystal structure analysis
−3
˚
Some details of the crystal structure analysis of 3a are
summarized in Table 3. The intensity data were collected
on a Bruker APEX II diffractometer with graphite-mono-
R1 = ꢁFo| − |Fcꢁ/Σ|Fo|; wR2 = [Σw(Fo − Fc2)2/Σw(Fo2)2]1/2
,
a
b
w = [σ2(Fo2) + (AP)2]−1, where P = (Max(Fo2,0) + 2Fc2)/3, and
c
2
A is a constant adjusted by the program; GoF = [Σw(Fo
−
˚
Fc2)2/(nobs −nparam)]1/2
.
chromatized MoKα radiation (λ = 0.71073 A) using ω and
ϕ scans (0.5◦ scan width). Reflections were corrected for
background, absorption, Lorentz and polarization effects.
The structure was solved by Direct Methods (SIR92 [9]) and
refined using SHELXL-97 [10].
stirred in a sealed tube at 120 ◦C for 16 h. The cold
reaction mixture was poured into 10 mL of H2O and
treated with 20 mL of CHCl3. The organic layer was
dried (Na2SO4), concentrated and purified by column chro-
matography (40 × 2 cm SiO2, petroleum ether, b. p. 40 –
70 ◦C). Crystallization from petroleum ether (b. p. 40 –
70 ◦C) yielded 3a as colorless crystals (985 mg, 55 %)
CCDC 815312 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif.
[1] J. E. Anthony, S. I. Khan, Y. Rubin, Tetrahedron Lett.
1997, 38, 3499 – 3502.
[2] D. Bruns, H. Miura, K. P. C. Vollhardt, Org. Lett. 2003,
5, 549 – 552.
The effects of the three activation barriers are superim-
posed by a temperature effect on the chemical shifts;
the resulting singlet at 365 K lies at lower field than
all four singlets at 260 K. All effects together pre-
vented us from a more exact evaluation by a line shape
analysis.
[3] Y. Rubin, Chimia 1998, 52, 118 – 126, and refs. cited
therein.
[4] J. Vincente, R. V. Shenoy, E. Martinez-Viviente, P. G.
Jones, Organometallics 2009, 28, 6101 – 6108.
[5] H. Detert, M. Lehmann, H. Meier, Materials 2010, 3,
3218 – 3330, and refs. cited therein.
[8] J. Peeling, B. W. Goodwin, T. Scha¨fer, J. B. Row-
botham, Can. J. Chem. 1973, 51, 2110 – 2117.
[9] A. Altomare, G. Cascarano, C. Giacovazzo, A. Gug-
liardi, M. C. Burla, G. Polidori, M. Camalli, SIR92, A
Program for Automatic Solution of Crystal Structures
by Direct Methods; see: J. Appl. Crystallogr. 1994, 27,
435.
[10] G. M. Sheldrick, SHELXL-97, Program for the Refine-
ment of Crystal Structures, University of Go¨ttingen,
Go¨ttingen (Germany) 1997. See also: G. M. Sheldrick,
Acta Crystallogr. 2008, A64, 112 – 122.
[6] H. Meier, H. C. Holst, Adv. Synth. Catal. 2003, 345,
1005 – 1011.
[7] Three slightly different rotations of 3b have to be con-
sidered: rotation of 6-CHCl2 leads to the exchange of
2-CHCl2 and 4-CHCl2 in 3b, rotation of 4-CHCl2 in 3b
leads to the exchange of 2-CHCl2 and 6-CHCl2 in 3b,
and only rotation of 2-CHCl2 in 3b leads to 3b → 3a.
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