1-Chloro-3,6-dimethoxy-2,5-dimethylbenzene and 1-chloro-3,6-dimethoxy-2,4- dimethylbenzene

Article abstract of DOI:10.1107/S0108270104013551

The title compounds, 1-chloro-3,6-dimethoxy-2,5-dimethylbenzene,(IIIa), and 1-chloro-3,6-dimethoxy-2,4-dimethylbenzene, (IIIb), both C₁₀H ₁₃ClO₂, were obtained from 2,5- and 2,6-dimethyl-1,4- benzoquinone, respectively, an

Full text of DOI:10.1107/S0108270104013551

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
sequence, for reasons which are not clear. Starting with (IIIa)
and (IIIb), we also synthesized unexpected dimers using
amidomethylation reactions (Wiedenfeld et al., 2004).
ISSN 0108-2701
1-Chloro-3,6-dimethoxy-2,5-dimethyl-
benzene and 1-chloro-3,6-dimethoxy-
2,4-dimethylbenzene
David J. Wiedenfeld, Vladimir N. Nesterov,* Mark A.
Minton and Crystal L. Montoya
Department of Natural Sciences, New Mexico Highlands University, Las Vegas,
NM 87701, USA
Isomers (IIIa) and (IIIb) have different substituents around
the methoxy groups on the adjacent atoms of the ring and
crystallize in different space groups (Figs. 1 and 2). In both
molecules, the methoxy groups each have different orienta-
tions with respect to the benzene ring. In both cases, one lies in
the plane of the ring and can participate in conjugation with
the aromatic system [torsion angles C2ÐC3ÐO2ÐC9 =
179.4 (4)ꢀ in (IIIa) and C1ÐC6ÐO1ÐC7 = 179.9 (4)ꢀ in
(IIIb)], and the second is almost perpendicular to the plane of
the aromatic ring [torsion angles C1ÐC6ÐO1ÐC7 = 86.9 (5)ꢀ
in (IIIa) and C2ÐC3ÐO2ÐC9 = 94.0 (4)ꢀ in (IIIb)].
Such different orientations of the methoxy groups about the
benzene ring in (IIIa) and (IIIb) account for the distortion of
the bond angles. Thus, we found an increase in the C3ÐO2Ð
C9 angle to 117.5 (4)ꢀ in (IIIa) and in C6ÐO1ÐC7 to
118.2 (3)ꢀ in (IIIb) for the in-plane methoxy group. For the
out-of-plane methoxy group, C6ÐO1ÐC7 and C3ÐO2ÐC9
are distinctly lower, at 114.7 (3)ꢀ in (IIIa) and 113.6 (3)ꢀ in
(IIIb). We have previously found such effects in related
compounds (Wiedenfeld et al., 2003, 2004). Such geometry is
usual for compounds containing OCH3 groups with different
orientations about aromatic rings (Gallagher et al., 2001).
Other bond lengths and angles in the title molecules have
expected values (Allen et al., 1987).
Correspondence e-mail: vnesterov@nmhu.edu
Received 13 April 2004
Accepted 4 June 2004
Online 30 June 2004
Thetitlecompounds,1-chloro-3,6-dimethoxy-2,5-dimethylben-
zene,(IIIa), and 1-chloro-3,6-dimethoxy-2,4-dimethylbenzene,
(IIIb), both C10H13ClO2, were obtained from 2,5- and 2,6-
dimethyl-1,4-benzoquinone, respectively, and are intermedi-
ates in the synthesis of ammonium quinone derivatives. The
isomers have different substituents around the methoxy
groups and crystallize in different space groups. In both
molecules, the methoxy groups each have different orienta-
tions with respect to the benzene ring. In both cases, one
methoxy group lies in the plane of the ring and can participate
in conjugation with the aromatic system, while the second is
almost perpendicular to the plane of the aromatic ring. The
CÐOÐC bond angles around these substituents are also
different: 117.5 (4) and 118.2 (3)ꢀ in (IIIa) and (IIIb),
respectively, when the methoxy groups lie in the plane of
the ring, and 114.7 (3) and 113.6 (3)ꢀ in (IIIa) and (IIIb),
respectively, when they are out of the plane of the ring.
Analysis of the crystal packing of compounds (IIIa) and
(IIIb) shows that there are very weak intermolecular contacts
Comment
We have been engaged in the synthesis of ammonium quinone
derivatives as electron acceptors for charge-transfer studies,
and had occasion to prepare the two chlorodimethoxydi-
methylbenzene isomers (IIIa) and (IIIb) as precursors to our
targets. The chlorine substituents were introduced in order to
prepare quinones with an electron-withdrawing group. These
compounds were synthesized in a two-step sequence, namely
treatment of a dimethylbenzoquinone with methanolic
hydrogen chloride followed by O-methylation. For example, in
the synthesis of (IIIa), 2,5-dimethyl-1,4-benzoquinone, (Ia),
was treated with methanolic hydrogen chloride to give a
quantitative yield of 2-chloro-4-methoxy-3,6-dimethylphenol,
(IIa). This latter species was then methylated under phase-
transfer conditions with dimethyl sulfate to give a 96% yield of
the diether (IIIa). The synthesis of (IIIb) was similar, but gave
lower yields along with more side products in each step of this
Figure 1
A view of the molecule of (IIIa), with the atom-numbering scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii.
o536 # 2004 International Union of Crystallography
DOI: 10.1107/S0108270104013551
Acta Cryst. (2004). C60, o536±o538

organic compounds
using 25:1 hexanes±EtOAc as eluant, afforded 1.92 g (96%) of pure
product as a colourless oil that crystallized slowly. After recrystalli-
zation from 10% EtOAc in hexane, the melting point was 321±322 K.
1H NMR (CDCl3, ꢀ): 6.56 (s, 1H, Ar-H), 3.79 (s, 3H, OCH3-6*), 3.76
(s, 3H, OCH3-3*), 2.29 (s, 3H, Ar-CH3-2*), 2.24 (s, 3H, Ar-CH3-5*);
13C NMR (CDCl3, ꢀ): 153.9 (Ar-C3), 148.0 (Ar-C6), 129.2 (Ar-C5),
128.9 (Ar-C1), 123.6 (Ar-C2), 110.8 (Ar-C4), 60.1 (OCH3-6), 55.9
(OCH3-3), 16.4 (Ar-CH3-5), 12.8 (Ar-CH3-2). For the preparation of
compound (IIIb), O-methylation of (IIb) was analogous to that for
(IIa). After recrystallization from 10% EtOAc in hexane, the melting
point was 323±324 K. 1H NMR (CDCl3, ꢀ): 6.61 (s, 1H, Ar-H), 3.85 (s,
3H, OCH3-6), 3.66 (s, 3H, OCH3-3), 2.33 (s, 3H, Ar-CH3-2), 2.28 (s,
3H, Ar-CH3-4); 13C NMR (CDCl3, ꢀ): 151.3 (Ar-C6), 150.9 (Ar-C3),
130.8 (Ar-C2), 129.3 (Ar-C4), 120.4 (Ar-C1), 111.3 (Ar-C5), 60.2
(OCH3-3), 56.3 (OCH3-6), 16.3 (Ar-CH3-4), 13.6 (Ar-CH3-2). For
X-ray analysis, crystals of both compounds were grown from 10%
ethyl acetate in hexanes by slow evaporation at room temperature.
X-ray investigations revealed that the crystals of these compounds
exhibit different behaviour under an X-ray beam. Thus, the structure
of compound (IIIa) was investigated several times, but the crystals
decomposed during the experiments, while crystals of (IIIb) did not
decay. For (IIIa), the crystal was coated with a two-component epoxy
glue, which successfully protected the crystal and prevented further
decay.
Figure 2
A view of the molecule of (IIIb), with the atom-numbering scheme.
Displacement ellipsoids are drawn at the 50% probability level and H
atoms are shown as small spheres of arbitrary radii.
Ê
[O1Á Á ÁH7B(x, y 1, z) = 2.54 A in (IIIa) and O1Á Á Á
H8B(1 x, 12 + y, 1 z) = 2.59 A in (IIIb)], which can be
Ê
considered to be weak hydrogen bonds that link molecules
Ê
in the crystals, with parameters O1Á Á ÁC7 = 3.461 (5) A, C7Ð
ꢀ
Ê
H7B = 0.96 A and C7ÐH7BÁ Á ÁO1 = 161 in (IIIa), and
Ê
Ê
O1Á Á ÁC8 = 3.524 (5) A, C8ÐH8B = 0.96 A and O1Á Á ÁC8Ð
H8B = 164ꢀ in (IIIb).
In the crystal structure of (IIIb), the intermolecular
distances Cl1Á Á ÁC5( x, 12 + y,
1
z) [3.587 (5) A] and
Compound (IIIa)
Ê
Cl1Á Á ÁC6( x, 12 + y, 1 z) [3.577 (5) A] are slightly greater
than the sum of the van der Waals radii (Rowland & Taylor,
1996) but shorter than in (IIIa), where the distance
Ê
Crystal data
C10H13ClO2
Mr = 200.65
Mo Kꢁ radiation
Cell parameters from 24
re¯ections
1
2
1
2
Ê
Orthorhombic, Pna21
Ê
Cl1Á Á ÁC4(x
,
y, z) is 3.613 (5) A. Such weak inter-
a = 14.490 (3) A
Ê
ꢂ = 11±12ꢀ
molecular interactions could play a signi®cant role in the
stability of the crystal, especially in the case of (IIIb), which is
more stable than (IIIa) under X-ray irradiation (see Experi-
mental). The other intermolecular distances in both crystals
are greater than the sums of the van der Waals radii of the
atoms.
1
b = 4.1470 (8) A
Ê
ꢃ = 0.34 mm
T = 295 (2) K
c = 16.848 (3) A
3
Ê
V = 1012.4 (3) A
Prism, colorless
0.50 Â 0.40 Â 0.30 mm
Z = 4
Dx = 1.316 Mg m
3
Data collection
Enraf±Nonius CAD-4
diffractometer
ꢂ/2ꢂ scans
2961 measured re¯ections
1507 independent re¯ections
1010 re¯ections with I > 2ꢄ(I)
Rint = 0.098
ꢂmax = 30.0ꢀ
h = 20 ! 20
k = 5 ! 0
Experimental
l = 0 ! 23
For the preparation of 2-chloro-3,6-dimethyl-4-methoxyphenol, (IIa),
2,5-dimethyl-1,4-benzoquinone, (Ia) (1.36 g, 10 mmol), was added to
an ice-cold solution of MeOH (70 ml) containing AcCl (7 ml, 0.1 mol)
and stirred overnight at room temperature. The solution was then
concentrated on a rotary evaporator and vacuum dried, giving 1.86 g
3 standard re¯ections
every 97 re¯ections
intensity decay: 3%
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.063
wR(F2) = 0.163
S = 1.03
1507 re¯ections
w = 1/[ꢄ2(Fo2) + (0.09P)2]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max < 0.001
1
(100%) of (IIa) as a pink crystalline solid, pure by NMR. H NMR
(DMSO-d6, ꢀ): 8.41 (s, 1H, OH), 6.72 (s, 1H, Ar-H), 3.71 (s, 3H,
OCH3), 2.19 (s, 3H, Ar-CH3-3*), 2.14 (s, 3H, Ar-CH3-6*); 13C NMR
(DMSO-d6, ꢀ): 150.4 (Ar-C4), 144.4 (Ar-C1), 123.7 (Ar-C3), 122.5
(Ar-C2), 121.4 (Ar-C6), 111.8 (Ar-C5), 56.0 (OCH3), 16.9 (Ar-CH3-6),
12.9 (Ar-CH3-3). 3-Chloro-2,6-dimethyl-4-methoxyphenol, (IIb), was
prepared analogously to (IIa), starting from 2,6-dimethyl-1,4-benzo-
quinone, (Ib). 1H NMR (CDCl3, ꢀ): 6.60 (s, 1H, Ar-H), 4.38 (br s, 1H,
OH), 3.83 (s, 3H, OCH3), 2.32 (s, 3H, Ar-CH3-2*), 2.24 (s, 3H, Ar-
CH3-6*). For the preparation of compound (IIIa), a solution of KOH
(1.98 g, 30 mmol, 3 equivalents at 85%) in H2O (30 ml) was added to
a solution of (IIa) (1.86 g, 10 mmol) and (n-Bu)4NBr (0.97 g, 3 mmol,
0.3 equivalents) in CH2Cl2 (30 ml). To the vigorously stirred mixture
was added Me2SO4 (2.85 ml, 30 mmol, 3 equivalents) in three
portions over 6 h. After a further 3 h, 2 N aqueous NaOH (12 ml) was
added and the mixture stirred overnight. Extractive work-up with
CH2Cl2 gave an orange oil which, after chromatography on silica gel
3
Ê
Áꢅmax = 0.60 e A
3
Ê
0.47 e A
Áꢅmin
=
122 parameters
H-atom parameters constrained
Absolute structure: Flack (1983),
with 20 Friedel pairs
Flack parameter = 0.18 (14)
Table 1
Selected geometric parameters (A, ) for (IIIa).
ꢀ
Ê
Cl1ÐC1
O1ÐC6
O1ÐC7
1.738 (3)
1.362 (5)
1.418 (5)
O2ÐC3
O2ÐC9
1.385 (5)
1.417 (6)
C6ÐO1ÐC7
114.7 (3)
179.4 (4)
C3ÐO2ÐC9
117.5 (4)
86.9 (5)
C9ÐO2ÐC3ÐC2
C7ÐO1ÐC6ÐC1
ꢁ
Acta Cryst. (2004). C60, o536±o538
David J. Wiedenfeld et al.
Two isomers of C10H13ClO2 o537

organic compounds
Table 2
Selected geometric parameters (A, ) for (IIIb).
Compound (IIIb)
ꢀ
Ê
Crystal data
3
Cl1ÐC1
O1ÐC6
O1ÐC7
1.735 (4)
1.358 (4)
1.421 (5)
O2ÐC3
O2ÐC9
1.378 (4)
1.426 (5)
C10H13ClO2
Mr = 200.65
Monoclinic, P21
a = 6.0740 (12) A
Dx = 1.307 Mg m
Mo Kꢁ radiation
Cell parameters from 24
re¯ections
Ê
Ê
b = 9.1250 (18) A
ꢂ = 11±12ꢀ
C6ÐO1ÐC7
118.2 (3)
94.0 (4)
C3ÐO2ÐC9
113.6 (3)
179.9 (4)
1
Ê
c = 9.4450 (19) A
ꢃ = 0.34 mm
T = 295 (2) K
ꢆ = 103.11 (3)ꢀ
V = 509.85 (18) A
Z = 2
3
Ê
C9ÐO2ÐC3ÐC2
C7ÐO1ÐC6ÐC1
Prism, colorless
0.45 Â 0.35 Â 0.25 mm
Data collection
ture: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL-
Plus; software used to prepare material for publication: SHELXL97.
Enraf±Nonius CAD-4
diffractometer
ꢂ/2ꢂ scans
1688 measured re¯ections
1559 independent re¯ections
999 re¯ections with I > 2ꢄ(I)
Rint = 0.056
ꢂ
max = 30.0ꢀ
h = 0 ! 8
k = 0 ! 12
l = 13 ! 12
The authors thank the NIH (grant No. S06 GM008066-31 to
DJW) for generous ®nancial support.
3 standard re¯ections
every 97 re¯ections
intensity decay: 3%
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GG1216). Services for accessing these data are
described at the back of the journal.
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.051
wR(F2) = 0.155
S = 1.07
1559 re¯ections
w = 1/[ꢄ2(Fo2) + (0.09P)2
+ 0.04P]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max < 0.001
References
3
Ê
Áꢅmax = 0.31 e A
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor,
R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1±19.
Enraf±Nonius (1989). CAD-4 Software. Version 5.0. Enraf±Nonius, Delft, The
Netherlands.
Flack, H. D. (1983). Acta Cryst. A39, 876±881.
3
Ê
0.20 e A
122 parameters
H-atom parameters constrained
Áꢅmin
=
Absolute structure: Flack (1983),
with 11 Friedel pairs
Flack parameter = 0.02 (13)
Gallagher, J. F., Hanlon, K. & Howarth, J. (2001). Acta Cryst. C57, 1410±1414.
Rowland, R. S. & Taylor, R. (1996). J. Phys. Chem. 100, 7384±7391.
Sheldrick, G. M. (1990). Acta Cryst. A46, 467±473.
Sheldrick, G. M. (1994). SHELXTL-Plus. PC Version 5.02. Siemens Analytical
X-ray Instruments Inc., Karlsruhe, Germany.
All H atoms were placed in geometrically calculated positions and
Ê
re®ned using a riding model, with CÐH distances of 0.93 A for
Ê
aromatic and 0.96 A for CH3 groups, and with Uiso(H) = 1.2Ueq(C).
È
Sheldrick, G. M. (1997). SHELXL97. University of Gottingen, Germany.
For both compounds, data collection: CAD-4 Software (Enraf±
Nonius, 1989); cell re®nement: CAD-4 Software; data reduction:
SHELXTL-Plus (Sheldrick, 1994); program(s) used to solve struc-
ture: SHELXS97 (Sheldrick, 1990); program(s) used to re®ne struc-
Wiedenfeld, D. J., Minton, M. A., Nesterov, V. N., Glass, D. R. & Montoya, C. L.
(2004). Tetrahedron Lett. 45, 4023±4026.
Wiedenfeld, D. J., Nesterov, V. N., Minton, M. A. & Glass, D. R. (2003). Acta
Cryst. C59, o700±o702.
ꢁ
o538 David J. Wiedenfeld et al.
Two isomers of C10H13ClO2
Acta Cryst. (2004). C60, o536±o538