Chlorination of 2,2,2,5-tetrachloro-6-methylbenzo[d]-1,3,2-dioxaphosphole

Article abstract of DOI:10.1070/MC2005v015n05ABEH002170

An NMR investigation has shown that the reaction of 2,2,2,5-tetrachloro-6- methylbenzo[d]-1,3,2-dioxaphosphole 2 with an excess of molecular chlorine occurs stepwise with high stereoselectivity to give 2,3,4,5,6,6-hexachloro-3- dichlorophosphoryl-5-methyl

Full text of DOI:10.1070/MC2005v015n05ABEH002170

, 2005, 15(5), 181–183
Chlorination of 2,2,2,5-tetrachloro-6-methylbenzo[d]-1,3,2-dioxaphosphole
Elena N. Varaksina,* Vladimir F. Mironov, Alfia A. Shtyrlina, Alexey B. Dobrynin, Igor A. Litvinov and
Alexander I. Konovalov
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of Sciences,
420088 Kazan, Russian Federation. Fax: +7 8432 73 2253; e-mail: vlena@iopc.knc.ru
DOI: 10.1070/MC2005v015n05ABEH002170
An NMR investigation has shown that the reaction of 2,2,2,5-tetrachloro-6-methylbenzo[d]-1,3,2-dioxaphosphole 2 with an excess
of molecular chlorine occurs stepwise with high stereoselectivity to give 2,3,4,5,6,6-hexachloro-3-dichlorophosphoryl-5-methyl-
cyclohex-1-ene 4, which then undergoes stabilization via a 3,3-sigmatropic shift of the dichlorophosphonate fragment to give
1,2,4,4,5,6-hexachloro-3-dichlorophosphoryl-5-methylcyclohex-1-ene 5. The configuration of the hydrolysis product of the latter
(1,2,4,4,5,6-hexachloro-5-methyl-3-phosphorylcyclohex-1-ene 6) was established by single crystal X-ray diffraction.
Selective incorporation of halogen atoms into organic mole-
cules is a problem of current interest. In most cases, this is
achieved using mild halogenating agents in various solvents;1
the use of accessible halogens is restricted by the low selec-
tivity of halogenation.1 The reaction of chlorine with benzene
derivatives such as phenols, anilines and pyrocatechols usually
occurs as electrophilic substitution to give either mixtures of
mono-, di- and trihalogen derivatives or a single product
(exhaustive chlorination).2 The reactions of methyl-substituted
anilines and phenols can occur not only as ordinary substitu-
tion but also as a rare process of violation of benzene ring
aromaticity resulting in mixtures of possible diastereomers of
polychlorinated cyclohexen-3-ones.3 Aromaticity violation also
occurs in the case of benzene chlorination under UV irradiation
to give hexachlorocyclohexane.2 We found previously4 that
the reaction of chlorine with 2,2,2-trichloro-4-methyl- and
2,2,2-trichloro-5-methylbenzo[d]-1,3,2-dioxaphospholes in a 1:1
ratio results in 2,2,2,5-tetrachloro-4-methyl- and 2,2,2,5-tetra-
chloro-6-methylbenzo[d]-1,3,2-dioxaphospholes 1 and 2, respec-
tively, in yields higher than 90%.
In this study, we found that, in the presence of an excess of
chlorine, chlorination does not stop, and dioxaphosphole 2 can
be further chlorinated with molecular chlorine under mild
conditions; this involves aromaticity violation of the benzene
fragment, that is, an addition reaction occurs.† We traced the
reaction path by 31P NMR spectroscopy and showed that the
reaction steps can be distinguished based on the kinetics. The
structures of certain intermediates were found by 13C NMR
spectroscopy.
Judging from the chemical shift dP –31.5, the first step involves
the formation of compound 3 containing a pentacoordinated
phosphorus atom. The violation of the benzene ring aromaticity
and the formation of a diastereoisomer containing four chiral
centres [C(3a), C(4), C(5), C(7a)] was reliably established based
on the 13C-{1H} and 13C NMR spectra of this compound. In the
molecule of phosphorane 3, five of the seven carbon atoms
resonate in the high-field region typical of the sp3-hydridised
carbon atom. The presence of two signals at d 95–101 evidenced
chlorine addition to the OC(3a)=C(7a)O bond and formation of
a C–C(3a)(Cl)–C(7a)(Cl)–O fragment.5 The nuclei of the C(3a)
and C(7a) ipso-carbon atoms are distinguishable owing to a
difference in the electronic effects of the chloromethylene and
alkenyl substituents [stronger deshielding of the C(3a) carbon
atom]. The signal of the other sp3-hybridised nucleus [C(4)] is
observed in the 13C-{1H} NMR spectrum‡ as a doublet with a
characteristic trans-constant 3JPCCC (18.9 Hz). When the spectrum
is recorded without decoupling from protons, this doublet is
additionally split into a doublet of quartets, which is only pos-
sible if there is a methyl group at the C(5) atom. The multiplicity
of the remaining signals for the C(6), C(7) and C(5) nuclei
suggests that the location of the double bond is C(6)=C(7).
There is no subsequent addition of chlorine to the double
bond of compound 3. During the storage of phosphorane 3 for
3–4 days at 20 °C, it is gradually converted into phosphate 4
(dP –2.1) via a non-classical variant of the Arbuzov reaction.
Phosphate 4 was obtained as a thick colourless oil. Its structure
was established on the basis of the 13C and 13C-{1H} NMR
spectra.† Unlike compound 3, the spectrum of phosphate 4 con-
tains only one signal, which is characteristic of the O–C(Cl)–C
2
environment and belongs to the C(3) nucleus (doublet, JPOC
15.2 Hz). In this case, the two low-field signals corresponding
to the resonance of the carbon atoms at the double bond have
the form of doublets due to the spin–spin coupling with the
†
General Procedures. Solvents and commercial reagents were purified
by conventional methods. All experiments were performed under an
atmosphere of dry argon. Melting points are uncorrected. Measurements
involved a Boetius melting point apparatus. NMR spectra were recorded
on Bruker MSL-400 (1H, 400 MHz; 13C, 100.6 MHz), Bruker WM-250
(1H, 250 MHz) and Bruker CXP-100 (31P, 36.48 MHz) spectrometers.
The dP values were determined relative to an external standard (H3PO4).
The dC and dH values were determined relative to an internal standard
(HMDS).
Chlorination of 2,2,2,5-tetrachloro-6-methylbenzo[d]-1,3,2-dioxa-
phosphole. A chlorine solution (1.9 g in 20 ml of dichloromethane,
–5 °C) was added to a stirred solution of phosphole 2 (6.5 g in 20 ml
of dichloromethane) in an argon atmosphere at –50 °C. A mixture of
compounds 2 (d –23.2) and 3 in a ratio of 3:2 was obtained in three days.
After six days, the ratio of compounds 2 and 3 was 1:6. Compound 3
was completely converted into phosphate 4 in two weeks (25 °C).
2,2,2,3a,4,5,6,7a-Octachloro-5-methyl-3a,7a,4,5-tetrahydrobenzo[d]-
1,3,2-dioxaphosphole 3. 13C NMR (hereinafter, the description of a
signal in 13C-{1H} NMR spectrum is given in parentheses) (CDCl3) d:
3
2
2
95.35 [ddd (d), C(7a), JHC(4)CC(7a) 2.3 Hz, JPOC(7a) 1.2 Hz, JHC(7)C(7a)
1.0–1.1 Hz], 122.94 [dd (s), C(7), 1JHC(7) 177.5 Hz, 4JHC(4)CCC(7) 1.4 Hz],
139.22 [dq (s), C(6), 2JHC(7)C(6) 5.4 Hz, 3JHC(8)CC(6) 4.3 Hz], 69.95 [m (s),
C(5)], 69.12 [ddq (d), C(4), 1JHC(4) 156.1 Hz, 3JPOCC(4) 18.9 Hz, 3JHC(8)CC(4)
2
3
3.5 Hz], 100.77 [ddd (d), C(3a), JPOC(3a) 5.9 Hz, JHC(7)CC(3a) 5.9 Hz,
2JHC(4)C(3a) 2.5 Hz], 25.38 [qd (s), C(8)H3, JHC(8) 132.7 Hz, JHC(4)CC(8)
1
3
3.1 Hz]. 31P-{1H} NMR (CDCl3) dP: –31.5.
2,3,4,5,6,6-Hexachloro-3-dichlorophosphoryl-5-methylcyclohex-1-ene
4. 13C NMR (CDCl3) d: 132.30 [dd (d), C(1), 1JHC(1) 180.4 Hz, 4JPOCCC(1)
1.4 Hz], 130.13 [dd (d), C(2), 2JHC(4)C(2) 5.1 Hz, 3JPOCC(2) 3.0 Hz], 96.91
2
3
2
[ddd (d), C(3), JPOC(3) 15.2 Hz, JHC(4)CC(3) 11.3 Hz, JHCC(3) 1.2 Hz],
71.16 [ddq (d), C(4), 1JHC(4) 158.5 Hz, 3JPOCC(4) 3.5 Hz, 2JHCC(4) 3.3 Hz],
75.37 [ddq (s), C(5), 3JHC(4)CC(5) 5.3 Hz, 2JHCC(5) 5.3 Hz, 2JHCC(5) 4.2 Hz],
87.97 [m (s), C(6), 3JHC(8)CC(6) 4.2 Hz, 3JHCCC(6) 2.7 Hz, 2JHCC(6) 1.5 Hz],
23.00 [qd (s), C(7), 1JHC(7) 132.7 Hz, 3JHC(4)CC(7) 4.4 Hz]. 31P-{1H} NMR
(CDCl3) dP: –1.3.
1,2,4,4,5,6-Hexachloro-3-dichlorophosphoryl-5-methylcyclohex-1-ene
5 was obtained by heating (180 °C, 5 min) of phosphate 4, as the yellow
1
viscous oil with 90% content (3.5 g), bp 145–148 °C (1 Torr). H NMR
(400 MHz, CDCl3) d: 5.94 [br. d, 1H, H(3), 3JPOCH 12.0 Hz], 5.03 [br. s,
1H, H(6)], 2.13 [br. s, 3H, Me]. 13C NMR (CDCl3) d: 126.62 [br. s (br. s),
1
C(1)], 132.00 [br. s (br. s), C(2)], 84.26 [dd (d), C(3), JHC(3) 162.3 Hz,
2JPOC(3) 7.8 Hz], 89.83 [br. m (d), C(4), 3JPOCC(4) 2.5 Hz], 73.95 [br. s (s),
1
C(5)], 65.39 [br. d (br. s), C(6), JHC(6) 163.4 Hz], 25.63 [br. q (br. s),
C(7)H3, 1JHC(7) 132.8 Hz]. 31P NMR (CDCl3) dP: 13.2 (d, 3JPOCH 12.0 Hz).
1,2,4,4,5,6-Hexachloro-5-methyl-3-phosphorylcyclohex-1-ene
6.
Colourless crystals of compound 6 (mp 211 °C) were obtained by
hydrolysis of phosphate 5 in aqueous acetone. 1H NMR (400 MHz,
[2H6]DMSO) d: 2.08 (br. s, 3H, Me), 5.60 [d, 1H, H(6), 3JPOCH 11.7 Hz],
6
5.69 [d, 1H, H(3), JPOCCCCH 1.1 Hz]. 31P NMR ([2H6]DMSO) dP: –2.7
(d, 3JPOCH 11.6 Hz).
Mendeleev Commun. 2005 181

, 2005, 15(5), 181–183
Cl(6A)
Cl
4
7
7
C(7A)
Cl
Cl
5
6
O
O
O
O
C(5A)
Cl2
3a
7a
7a
3a
*
*
C(6A)
C(7B)
C(5B)
PCl3
PCl3
5
6
*
Cl(5A)
C(4A)
Me
Cl
Cl(5B)
C(6B)
*
Cl(4A)
Cl(1A)
Cl(6B)
Me
4
C(1A)
Cl(3B)
Cl
Cl(3A)
Cl
C(2A)
Cl(4B)
C(3A)
C(4B)
C(1B)
2
3
Cl(1B)
C(3B)
O(1B)
O(1A)
P(1A)
O(2A)
C(2B)
Cl(2A)
Cl
O(3B)
Cl
1
1
C(11B)
O(4B)
S(1B)
Cl O
Cl
Cl O
6
2
6
2
O(4A)
Cl(2B)
Cl
Me
Cl
∆
*
*
P(1B)
O(2B)
O(3A)
5
3
5
3
PCl2
PCl2
O(9A)
*
C(11A)
*
*
Me
Cl
*
O(10B)
4
O
O
4
Cl
C(12B)
S(1A)
O(10A)
Cl Cl
Cl
O(9B)
C(12A)
4
5
Cl
Figure 1 Molecular geometry 6A and 6B in a crystal. Selected bond
lengths (d, Å): Cl(2A)–C(2A) 1.67(1), Cl(1A)–C(1A) 1.68(1), Cl(6A)–
C(6A) 1.78(1), Cl(5A)–C(5A) 1.84(1), Cl(3A)–C(4A) 1.77(1), Cl(4A)–
C(4A) 1.76(1), Cl(2B)–C(2B) 1.70(1), Cl(6B)–C(6B) 1.86(2), P(1A)–
O(1A) 1.56(1), P(1A)–O(3A) 1.52(1), P(1A)–O(2A) 1.54(1), P(1A)–
O(4A) 1.50(1), P(1B)–O(1B) 1.58(1), P(1B)–O(2B) 1.46(1), P(1B)–O(4B)
1.58(1), P(1B)–O(3B) 1.49(1), O(1A)–C(3A) 1.47(1), O(1B)–C(3B) 1.46(1),
C(1A)–C(2A) 1.31(2), C(1B)–C(2B) 1.34(2), C(2A)–C(3A) 1.55(2),
C(2B)–C(3B) 1.50(2), C(1A)–C(6A) 1.51(1), C(5A)–C(6A) 1.65(2),
C(5B)–C(6B) 1.50(2), C(5A)–C(7A) 1.64(2), C(5B)–C(7B) 1.57(2).
Selected bond angles (j/°): O(1A)–P(1A)–O(3A) 103.6(6), O(2A)–P(1A)–
O(3A) 111.4(7), O(1A)–P(1A)–O(4A) 107.8(6), O(1A)–P(1A)–O(2A)
110.6(6), O(3A)–P(1A)–O(4A) 106.4(7), O(2A)–P(1A)–O(4A) 116.2(7),
O(1B)–P(1B)–O(4B) 102.4(6), O(2B)–P(1B)–O(3B) 117.6(7), O(3B)–
P(1B)–O(4B) 107.8(6), O(1B)–P(1B)–O(3B) 107.2(6), P(1B)–O(1B)–
C(3B) 123.2(8). Selected torsion angles (t/°): O(4A)–P(1A)–O(1A)–C(3A)
113(1), O(4B)–P(1B)–O(1B)–C(3B) 119.2(9), P(1A)–O(1A)–C(3A)–C(2A)
–112(1), P(1B)–O(1B)–C(3B)–C(2B) 114(1), C(3A)–C(2A)–C(1A)–C(6A)
10(2), Cl(2A)–C(2A)–C(3A)–O(1A) 43(1), Cl(5A)–C(5A)–C(6A)–Cl(6A)
158.4(6), C(1A)–C(6A)–C(5A)–Cl(5A) –78.(1), Cl(1B)–C(1B)–C(6B)–
C(5B) –173(1), C(3A)–C(4A)–C(5A)–C(6A) –54(1), C(2B)–C(1B)–C(6B)–
Cl(6B) –115(1), C(2B)–C(1B)–C(6B)–C(5B) 12(2), C(1A)–C(2A)–C(3A)–
C(4A) –24(2), C(1A)–C(2A)–C(3A)–O(1A) –147(1), Cl(6B)–C(6B)–
C(5B)–C(4B) 88(1), C(1B)–C(6B)–C(5B)–C(4B) –37(2), Cl(1A)–C(1A)–
C(6A)–Cl(6A) –73(1), C(1B)–C(6B)–C(5B)–Cl(5B) 78(1), C(3B)–C(4B)–
C(5B)–C(6B) 54(2), C(6B)–C(5B)–C(4B)–Cl(4B) –66(1), C(2A)–C(3A)–
C(4A)–C(5A) 46(1), C(2A)–C(1A)–C(6A)–Cl(6A) 107(1), C(2A)–C(1A)–
C(6A)C(5A) –16(2), Cl(3A)–C(4A)–C(3A)–C(2A) –75(1), Cl(4A)–C(4A)–
C(3A)–O(1A) –68(1), Cl(3A)–C(4A)–C(3A)–O(1A) 48(1), Cl(5B)–C(5B)–
C(4B)–C(3B) –57(1), Cl(6A)–C(6A)–C(5A)–C(4A) –83(1), C(5A)–C(4A)–
C(3A)–O(1A) 169(1), Cl(2B)–C(2B)–C(3B)–C(4B) –160(1), C(1B)–
C(2B)–C(3B)–C(4B) 146(1), C(1B)–C(2B)–C(3B)–C(4B) 26(2).
1
Cl
Cl O
6
2
H2O
*
*
5
3
P(OH)2
*
Me
Cl
4
O
Cl Cl
6
phosphorus atom. Moreover, the C(4), C(5) and C(6) nuclei
that have a spin–spin coupling with the methyl-group protons
resonate at strong fields characteristic of sp3-hybridised carbon
atoms. At this step (the conversion of phosphorane 3 to phos-
phate 4), the allylic rearrangement is accompanied by the
regioselective cleavage of the C(7a)–O bond and the formation
of a phosphoryl group. The regiochemistry of the process is
probably more consistent with a higher stability of the inter-
mediate allylic carbocation with a positive charge at the C(7a)
atom than at the C(3a) atom.
Prolonged storage of phosphate 4 at 20 °C or with heating
results in an unusual 3,3-sigmatropic shift of the dichloro-
phosphate group; however, it may be regarded as a variant of
the Claisen 3,3-rearrangement.6 According to NMR spectra,
phosphate 5 is formed as a single diastereomer, in which the
P–O bond is hydrolysis-resistant. X-ray diffraction data for
hydrolysis product 6 (Figure 1) suggest that a single crystal
contains two enantiomers 6A and 6B in a 1:1 ratio, in which the
configurations of the C(3), C(5) and C(6) atoms are R, S, S and
S, R, R, respectively.‡ Compound 6 forms crystals as a salt
with DMSO and a solvate with water. The carbon ring in the
molecule of 6A has a semichair conformation: the four-atom
fragment C(6A)C(1A)C(2A)C(3A) is planar [to within 0.08(1) Å],
and the C(4A) and C(5A) atoms deviate by –0.31(1) and 0.31(1) Å
on both sides of the plane; in the molecule of 6B, this is a
semichair approaching a sofa: the four-atom fragment C(6B)-
C(1B)C(2B)C(3B) is planar [to within 0.02(1) Å], and the C(5B)
and C(4B) atoms deviate by –0.50(2) and 0.17(1) Å, respec-
tively, from the plane. The deviation of these atoms on different
sides allows one to consider this conformation as a semichair.
However, the very small deviation of the C(4B) atom [0.17(1) Å]
from the C(6B)C(1B)C(2B)C(3B) plane also allows us to con-
sider that the five-atom fragment C(6B)C(1B)C(2B)C(3B)C(4B)
is approximately planar and the ring conformation is a sofa.
The lengths of the C–Cl bonds at the C=C double bond are
shortened due to the effect of the phosphorus-containing sub-
stituents at the C(1) carbon atom [Cl(1A)–C(1A) 1.67(1) Å,
Cl(2A)–C(2A) 1.68(1) Å, Cl(1B)–C(1B) 1.71(1) Å, Cl(2B)–C(2B)
1.65(1) Å]. Since the crystal structure incorporates four solvate-
type solvent molecules (2DMSO and 2H2O), the crystal contains
multiple classical hydrogen bonds of the O–H···O type, which
result in the formation of infinite layers along one of the crys-
tallographic axes.
Thus, the reaction of 2,2,2,5-tetrachloro-6-methylbenzo[d]-
1,3,2-dioxaphosphole 2 with chlorine is the first example of
chlorination of an annelated 1,3,2-diheterocyclane at an aromatic
fragment, which occurs under mild conditions without addi-
tional stimulation by catalysis or irradiation. Apart from the
unusually facile aromaticity violation and allylic rearrangement,
the previously unknown 3,3-sigmatropic shift of the phosphoryl
group also occurs. This reaction is a convenient method for
the stereoselective synthesis of hardly accessible polyfunctional
cyclohexene derivatives.
‡
X-ray crystallography of compound 6: 2C7H6Cl6O4P·2C2H7OS·2H2O,
M = 494.95, triclinic, space group P1, a = 8.756(8), b = 10.472(8)
and c = 21.64(2) Å, a = 102.04(7)°, b = 99.18(7)°, g = 94.24(7)°, V =
= 1904(3) Å3, Z = 2, dcalc = 1.727 g·cm–3. Cell parameters and intensities
of 4449 independent reflections (2077 with I ³ 2s) were measured on
an Enraf-Nonius CAD-4 diffractometer in the w/2q-scan mode, q £ 57.3°,
using CuKα radiation with a graphite monochromator. Data corrections
were not applied (mMo 10.3 cm–1). The structure was solved by a direct
method using the SIR program7 and refined by the full matrix least-
squares using the SHELXL97 program.8 All non-hydrogen atoms were
refined anisotropically. The hydrogen atoms were included in the
calculated positions with thermal parameters 30% larger than those
of the atoms to which they were attached. The final residuals were
R = 0.1351 and Rw = 0.4048. All calculations were performed on a PC
using the WinGX program.9 Determination of cell parameters, data
collection and data reduction were performed on an Alpha Station 200
computer using the MoLEN program.10 All the figures were made using
the PLATON program.11
Atomic coordinates, bond lengths, bond angles and thermal param-
eters have been deposited at the Cambridge Crystallographic Data Centre
(CCDC). These data can be obtained free of charge via www.ccdc.cam.uk/
conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336 033; or deposit@ccdc.cam.ac.uk).
Any request to the CCDC for data should quote the full literature citation
and CCDC reference number 274794. For details, see ‘Notice to Authors’,
Mendeleev Commun., Issue 1, 2005.
This study was supported by the Russian Foundation for
Basic Research (project no. 03-03-32542).
182 Mendeleev Commun. 2005

, 2005, 15(5), 181–183
8
G. M. Sheldrick, SHELXL-97. Program for the Refinement of Crystal
Structures, University of Göttingen, 1997.
L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837.
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Received: 13th April 2005; Com. 05/2493
Mendeleev Commun. 2005 183