The X-ray Structures of 2,4-Dibromothiazole and 2,4-Diacetyl-5-bromothiazole

Article abstract of DOI:10.1007/s10870-015-0615-x

2,4-Dibromothiazole [orthorhombic, a = 6.700 (10), b = 16.21 (3), c = 5.516 (8) ?, space group Fmm2] shows a disordered crystal structure with molecules randomly oriented with respect to the direction of the Br-C(2)-N-C(2)-Br unit and the remaining ring atoms S(3) and C(3)H showing mixed occupancy. 2,4-Diacetyl-5-bromothiazole [triclinic, a = 4.040 (2), b = 8.254 (5), c = 13.208 (8) ?, α = 96.191 (17), β = 93.865 (16), γ = 94.067 (11)°, space group P-1] shows a structure dominated by halogen bonding, intramolecular between 4-COMe and 5-Br and intermolecular between 2-COMe of one molecule and 5-Br of the next. Graphical Abstract: 2,4-Dibromothiazole is disordered in the crystal structure with molecules randomly oriented either way round as shown. There is evidence for unusual intramolecular, and perhaps also intermolecular, halogen bonding between Br and C = O in the structure of 2,4-diacetyl-5-bromothiazole.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-015-0615-x

J Chem Crystallogr (2015) 45:461–465
DOI 10.1007/s10870-015-0615-x
ORIGINAL PAPER
The X-ray Structures of 2,4-Dibromothiazole and 2,4-Diacetyl-5-
bromothiazole
Kati M. Aitken1 R. Alan Aitken1 Callum I. MacGregor1 Mohamed D. M. Traore1
Alexandra M. Z. Slawin1
•
•
•
•
Received: 18 November 2014 / Accepted: 3 November 2015 / Published online: 16 November 2015
Ó The Author(s) 2015. This article is published with open access at Springerlink.com
N
Abstract 2,4-Dibromothiazole [orthorhombic, a = 6.700
˚
(10), b = 16.21 (3), c = 5.516 (8) A, space group Fmm2]
N
Br
O
Br
Br
or
Br
S
S
shows a disordered crystal structure with molecules ran-
domly oriented with respect to the direction of the Br–
C(2)–N–C(2)–Br unit and the remaining ring atoms S(3)
and C(3)H showing mixed occupancy. 2,4-Diacetyl-5-
bromothiazole [triclinic, a = 4.040 (2), b = 8.254 (5),
3.14 Å
O
N
S
O
N
O
S
Br
Br
3.35 Å
˚
c = 13.208 (8) A, a = 96.191 (17), b = 93.865 (16),
c = 94.067 (11)°, space group P-1] shows a structure
dominated by halogen bonding, intramolecular between
4-COMe and 5-Br and intermolecular between 2-COMe of
one molecule and 5-Br of the next.
Keywords Thiazole Á Bromothiazole Á Disorder Á
Halogen bonding
Graphical Abstract 2,4-Dibromothiazole is disordered
in the crystal structure with molecules randomly oriented
either way round as shown. There is evidence for unusual
intramolecular, and perhaps also intermolecular, halogen
bonding between Br and C = O in the structure of 2,4-
diacetyl-5-bromothiazole.
Introduction
Some time ago we reported the synthesis of 2,4-di-
acetylthiazole 1, a compound of interest for its flavour and
aroma properties, by bromination of diethylthiazole 2 to
give 3 followed by treatment with silver nitrate in aqueous
ethanol (Scheme 1) [1]. In the course of this work, several
new brominated thiazole derivatives were obtained, and we
present here the X-ray structure determination of two of
these of particular interest: 2,4-dibromothiazole 4 and 2,4-
diacetyl-5-bromothiazole 6. Compound 4 was prepared as a
potential alternative precursor to 1 using lithium/halogen
exchange followed by acetylation with N-acetylmorpholine
[2], but in agreement with the literature reports, even with
two or more equivalents of reagents under a variety of
conditions, this proceeded only once on the 2-position and
the 4-positon was unreactive. The traditional synthesis of 4
requires treatment of the commercially available thiazo-
lidine-2,4-dione 5 with a large excess of expensive POBr3
but we obtained it using the recently reported improved
synthesis involving reaction of 5 with P2O5 and Bu4NBr in
toluene [3]. In our reported synthesis of 1 [1], the
Electronic supplementary material The online version of this
article (doi:10.1007/s10870-015-0615-x) contains supplementary
material, which is available to authorized users.
& R. Alan Aitken
raa@st-and.ac.uk
1
EaStCHEM School of Chemistry, University of St Andrews,
St Andrews, Fife KY16 9ST, UK
123

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J Chem Crystallogr (2015) 45:461–465
nitrate (111.6 g, 657 mmol) in water (170 cm3) and the
mixture was heated under reflux for 20 min. It was cooled
and acidified with 12 M hydrochloric acid (190 cm3). The
solid silver salts were filtered off and the filtrate was
evaporated down to 150 cm3, neutralised with aqueous
NaHCO3, and extracted with CH2Cl2 (3 9 50 cm3). The
extracts were dried (MgSO4) and evaporated and the resi-
due was subjected to column chromatography (SiO2, Et2O/
hexane, 1:1). Three fractions were obtained:
N
N
H
N
Br
Br
Br
Br
P2O5, Bu4NBr
O
O
S
S
S
4
4a
5
AgNO3
aq EtOH
Br
Br
O
O
Br
Br
Br
Br
NBS
N
N
N
S
3
+
S
S
S
1
+
2
Br
Br
Br
Br
O
O
O
Br
N
N
S
N
I
Br
Br
6
+
8
+
N
S
2-Acetyl-5-bromo-4-(1-ethoxyethyl)thiazole 7
Br
I
OEt
10
N
S
S
4.31 g (12 %) as a colourless liquid, bp 158–160 °C (oven
Br
1
7
9
temp)/3 Torr. H NMR (CDCl3) d 1.21 (3H, t, J 7), 1.57
(3H, d, J 7), 2.69 (3 H, s), 3.39 and 3.49 (2H, AB pattern of
q, J 9, 7) and 4.78 (1 H, q, J 7), 13C NMR (CDCl3) d 15.3
(CH2Me), 20.4 (MeCHOEt), 25.4 (MeCO), 64.5 (CHOEt),
Scheme 1 Synthetic routes used to compounds 1, 4, 6 and 7 and
structure of 10
71.1 (OCH2), 115.0 (C-5), 157.8 (C-4), 166.9 (C-2) and
79
bromination of 2 gave a range of other byproducts besides
the desired tetrabromide 3. Treating the mixture with silver
nitrate in aqueous ethanol gave mainly 1 and, as the most
volatile component present, this was separated in pure form
by vacuum distillation, but in only 49 % yield. If the crude
mixture was instead subjected to column chromatography
it allowed isolation of compounds 6 and 7, respectively
derived from 8 and 9. There is therefore a competition
between bromination at the 4-ethyl group and ring bromi-
nation at position 5 in 2 resulting in the observed mixture
of three products. Compound 7 was obtained after distil-
lation as a colourless liquid while compound 6 was
recrystallised from hexane to afford a sample suitable for
X-ray diffraction.
191.2 (CO); HRMS m/z found: 299.9668. C9H BrNaNO2S
12
81
(M ? Na) requires 299.9670; found: 301.9641. C9H
12
BrNaNO2S (M ? Na) requires 301.9649.
2,4-Diacetyl-5-bromothiazole 6
1.80 g (5.5 %) as colourless crystals, mp 83–84 °C;
(Found: C, 33.9; H, 2.0; N, 5.3. C7H6BrNO2S requires C,
1
33.9; H, 2.4; N, 5.6 %); H NMR (CDCl3) d 2.708 (3H, s,
2-COMe) and 2.724 (3H, s, 4-COMe); 13C NMR (CDCl3) d
25.1 (2-COMe), 28.7 (4-COMe), 122.7 (C-5), 150.1 (C-4),
165.2 (C-2), 190.6 (CO, 2-COMe), 192.6 (CO, 4-COMe)
[assignment of 1H and 13C NMR signals supported by
HMBC study]; HRMS m/z found: 269.9191. C7H679
BrNNaO2S (M ? Na) requires 269.9200; found: 271.9185.
C7H861BrNNaO2S (M ? Na) requires 271.9180.
Experimental
2,4-Dibromothiazole 4
2,4-diacetylthiazole 1
This compound was prepared by reaction of commercially
available thiazolidine-2,4-dione 5 with P2O5 and Bu4NBr
in boiling toluene [3]. It was obtained directly as colourless
crystals suitable for X-ray diffraction which gave the
12.6 g (57 %) as colourless crystals, mp 65–68 °C, data as
reported in [1].
Data were collected using a Rigaku MM007 RA and a
Mercury CCD (confocal optics Mo-Ka radiation) at 93 K.
Intensity data were collected using x// steps accumulating
area detector frames spanning at least a hemisphere of
reciprocal space (data were integrated using CrystalClear).
All data were corrected for Lorentz, polarisation and long-
term intensity fluctuations. Absorption effects were cor-
rected on the basis of multiple equivalent reflections. The
structure was solved by direct methods and refined by full-
matrix least-squares against F2 (SHELXTL). Hydrogen
atoms were assigned riding isotropic displacement param-
eters and constrained to idealised geometries. Table 1
summarises the X-ray data.
1
following data: mp 81–82 °C (81.1–82.4 °C [3]; H NMR
(CDCl3) d 7.21 (1H, s); 13C NMR d 120.8 (CH), 124.3
(C-4) and 136.3 (C-2).
2,4-Diacetyl-5-bromothiazole 6 and 2-Acetyl-5-
bromo-4-(1-ethoxyethyl)thiazole 7
A solution of the mixture of products from NBS bromi-
nation of 2,4-diethylthiazole 2 (60.55 g, 131.4 mmol) in
ethanol (500 cm3) was mixed with a solution of silver
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J Chem Crystallogr (2015) 45:461–465
463
Table 1 Crystal data and
structure refinement details for 4
and 6
4
6
CCDC deposit no.
1033511
1033512
C7H6BrNO2S
248.09
Empirical formula
Formula weight
Crystal system
Space group
C3HBr2NS
242.92
Orthorhombic
Fmm2
Triclinic
P-1
Temperature (K)
Crystal form
93(2)
93(2)
Colourless prism
0.10 9 0.02 9 0.02 mm
Colourless prism
0.15 9 0.15 9 0.15 mm
˚
a = 6.700 (10) A
˚
a = 4.040 (2) A
Unit cell dimensions
˚
b = 16.21 (3) A
˚
b = 8.254 (5) A
˚
c = 5.516 (8) A
˚
c = 13.208 (8) A
a = 96.191 (17)°
b = 93.865 (16)°
c = 94.067 (11)°
435.5 (4)
3
˚
Volume (A )
599.0 (16)
4
Z
2
Dc (g cm-3
)
2.694
13.79 mm-1
1.892
4.928 mm-1
Absorption coefficient
˚
˚
Radiation type, wavelength
Mo Ka, 0.71073 A
Mo Ka, 0.71073 A
F(000
)
448
244
h qamce
2.51–25.35°
-7 B h B 7, -19 B k B 14,
-6 B l B 6
874/308
2.50–27.50°
-4 B h B 4, -9 B k B 9,
-15 B l B 15
6521/1573
0.0978
Limiting indices
Reflections collected/unique
Rint
0.1615
Data/restraints/parameters
Data with I [ 2r(I))
Goodness of fit on F2
R1, wR2 (data with I [ 2r(I))
R1, wR2 (all data)
308/14/29
1573/0/111
1355
278
1.110
0.925
0.0940, 0.2337
0.1011, 0.2545
1.030 and -1.729
0.00 (9)
0.0543, 0.1367
0.0564, 0.1374
1.944 and -1.351
–
-3
˚
Largest diff. peak/hole (e A
)
Flack parameter
Table 2 Bond lengths and angles for 4
˚
Length (A)
Bond
Atoms
Angle (°)
Br(2)–C(2)
C(2)–N(1)
C(2)–C(3)
C(3)–S(3)
S(3)–C(2)
1.91 (5)
1.35 (6)
1.35 (2)
1.8 (1)
Br(2)–C(2)–N(1)
C(2)–N(1)–C(2)
Br(2)–C(2)–S(3)
N(1)–C(2)–S(3)
C(2)–S(3)–C(3)
S(2)–C(3)–C(2)
C(3)–C(2)–N(1)
C(3)–C(2)–Br(2)
118 (4)
105 (5)
123 (2)
119 (4)
91 (3)
1.61 (5)
103 (4)
123 (5)
120 (3)
Fig. 1 The molecular structure of 4 showing numbering system used
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J Chem Crystallogr (2015) 45:461–465
Results and Discussion
The molecular structure of 4 is shown in Fig. 1. As
expected it is perfectly planar, but is disordered with
respect to the orientation of the molecule, with forms 4 and
4a having a sufficiently similar overall shape, dominated
by the large bromine atoms, to fit equally well into the
lattice. The bond lengths and angles (Table 2) obtained for
the Br–C–N–C–Br section of the molecule are therefore
mean values for the hybrid between structures 4 and 4a.
There have been few previous structural studies on simple
halogenated thiazoles, and among all the possible mono-,
di- and trihalothiazoles the only one to be previously
characterised by X-ray diffraction is 2,5-diiodothiazole 10
[4]. Although one could envisage a similar disorder with
the I–C–S–C–I unit randomly arranged and mixed occu-
pancy of N and 4-CH, no such phenomenon occurs in that
case.
Fig. 2 The molecular structure of 6 showing numbering system used
Table 3 Bond lengths, angles and torsion angles for 6
˚
Length/A
When we come to the structure of compound 6 (Fig. 2;
Table 3), the whole molecule including the two acetyl
groups is essentially planar. There is some evidence for
both intra- and intermolecular halogen bonding between
the C–Br and the C(4)–acetyl of the same molecule and the
C(2)–acetyl of the next molecule. The pattern is shown in
Fig. 3 and the parameters are given in Table 4. Halogen
bonding in general has been of considerable recent interest
[5–8] and such an interaction between bromine and car-
bonyl oxygen has been studied both computationally [9,
10] and experimentally [11] in simple molecules, and by
surveying complex biological structures [12]. However the
two interactions here show unusual features. The
intramolecular interaction with O(8) results in a definite
Bond
Atoms
Angle/°
C(2)–S(1)
S(1)–C(5))
C(5)–C(4)
C(4)–N(3)
N(3)–C(2)
C(5)–Br(1)
C(4)–C(8)
C(8)–O(8)
C(8)-C(9)
C(2)–C(6)
C(6)–O(6)
C(6)–C(7)
1.729 (6)
1.710 (5)
1.382 (8)
1.383 (7)
1.301 (7)
1.864 (5)
1.481 (8)
1.206 (7)
1.501 (8)
1.495 (8)
1.204 (7)
1.502 (8)
S(1)–C(2)–C(3)
C(2)–N(3)–C(4)
N(3)–C(4)–C(5)
C(4)–C(5)–S(1)
C(5)–S(1)–C(2)
115.8 (4)
111.0 (4)
113.3 (5)
111.5 (4)
88.4 (3)
N(3)–C(4)–C(8)–O(8)
N(3)–C(2)–C(6)–O(6)
179.0 (5)
176.4 (5)
Fig. 3 Halogen bonding pattern in the crystal structure of 6 viewed along the a axis
Table 4 Geometric parameters
for intra and intermolecular
D–BrÁÁÁO = A
d (D–Br)
d (BrÁÁÁO)
\(DBrO)
\(BrOA)
halogen bonding in 6
C(5)–Br(1)ÁÁÁO(8) = C(8)
C(5)–Br(1)ÁÁÁO(6) = C(6)
1.864 (5)
1.864 (5)
3.140 (5)
3.352 (5)
67.0 (2)
95.2 (3)
160.0 (2)
112.8 (3)
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J Chem Crystallogr (2015) 45:461–465
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shortening of the interatomic distance compared to the sum
˚
˚
of van der Waals radii (ca. 3.37 A [12] or 3.35 A [13]) but
the angles involved, both at bromine and oxygen, are far
from the normally accepted optimal range. On the other
hand the intermolecular interaction with O(6) results in a
very marginal shortening in interatomic distance compared
to the sum of van der Waals radii, despite the angles being
much more favourable.
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