Synthesis of bromine-substituted cyclohexenylphosphonates

Article abstract of DOI:10.1134/S1070363212040068

Bromination of cyclohexa-1,4-dienylphosphonates yields new substituted 4,5-dibromocyclohexene-1-phosphonates. The structure of obtained compounds was confirmed by ¹H, ¹³C and ³¹P NMR spectra.

Full text of DOI:10.1134/S1070363212040068

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 4, pp. 652–655. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © K.S. Titov, N.I. Svintsitskaya, B.I. Ionin, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 4, pp. 566–569.
Synthesis of Bromine-Substituted Cyclohexenylphosphonates
K. S. Titov, N. I. Svintsitskaya, and B. I. Ionin
St. Petersburg State Technological Institute, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: borisionin@mail.ru
Received December 20, 2011
Abstract—Bromination of cyclohexa-1,4-dienylphosphonates yields new substituted 4,5-dibromocyclohexene-
1-phosphonates. The structure of obtained compounds was confirmed by 1H, 13C and 31P NMR spectra.
DOI: 10.1134/S1070363212040068
The phosphorus derivatives of cyclohexane are
reactive compounds with a broad synthetic opportunites
which are also of interest in the study of theoretical
problems of organic chemistry. It has been shown that
the oxidation of cyclohexa-1,4-diene diphosphonates
with KMnO4/Al2O3 in acetone leads to the formation
of substituted o-benzene diphosphonates [1], which are
convenient synthons for the corresponding phosphines
[2]. The oxidative chlorophosphorylation of cyclo-
hexane allowed us the preparation of cyclohexane- and
cyclohexene-1-phosphonic acids dichlorides starting
from available materials. The obtained compounds are
suitable for the subsequent conversion into other
derivatives. In particular, their reactions with ZnF2
give the highly reactive phosphonic acids difluorides
[3]. In continuation of the studies on the synthesis and
reactivity of the phosphorus-containing carbocyclic
compounds of the cyclohexane series, in this work we
performed the bromination of cyclohexa-1,4-diene
diphosphonates.
The starting cyclohexa-1,4-diene diphosphonates
Ia–If were obtained via Diels–Alder reaction of
acetylene diphosphonates with classical donor 1,3-
alkadienes: divinyl, isoprene, piperilene, and 2,3-
dimethylbuta-1,3-diene [2].
R1
X
CR1 CR2 CHR3
CX
(MeO)2PC
O
CH2
R2
Y
R3
Ia_If
R1 = R2 = Me, R3 = H, X = Y = PO(OMe) (а); R1 = R2 = H, R3 = Me, X = Y = PO(OMe) (b); R1 = Me, R2 = R3 = H, X = Y =
PO(OMe) (c); R1 = R2 = Me, R3 = H, X = PO(OMe), Y = Cl (d); R1 = R2 = H, R3 = Me, X = PO(OMe), Y = Cl (e); R1(2)
Me, R2(1) = R3 = H, X = PO(OMe), Y = Cl (f).
=
The bromination of cyclohexa-1,4-dienylphospho-
IIa–IIf. The reaction occurs as a chemoselective
nates Ia–If proceeds readily to give the corresponding
electrophilic addition at the electron rich double bond
of cyclohexa-1,4-diene.
cyclohex-1-ene-1-phosphonates
dibromoderivatives
R1
R1
R2
X
Y
X
Br
Br
R2
Y
R3
IIa_IIf
R3
Ia_If
R1 = R2 = Me, R3 = H, X = Y = PO(OMe) (а); R1 = R2 = H, R3 = Me, X = Y = PO(OMe) (b); R1 = Me, R2 = R3 = H, X = Y =
PO(OMe) (c); R1 = R2 = Me, R3 = H, X = PO(OMe), Y = Cl (d); R1 = R2 = H, R3 = Me, X = PO(OMe), Y = Cl (e); R1(2)
Me, R2(1) = R3 = H, X = PO(OMe), Y = Cl (f).
=
652

653
SYNTHESIS OF BROMINE-SUBSTITUTED CYCLOHEXENYLPHOSPHONATES
2
The bromination was carried out in a methylene
chloride medium by stirring equimolar amounts of the
starting materials at 0°C.
nucleus JCP cannot be determined probably due to the
insufficient resolution.
1
In the H NMR spectrum of IIa (Fig. 2) there are
The reaction progress was monitored by NMR
spectroscopy. Thus, in the 13C NMR spectra, the most
informative for this type of compounds, after the
reaction completion the singlet signals of sp2-
hybridized carbon atoms C4 and C5 of the initial
two signals of the methylene protons of cyclohexene
ring as an AB-system (2JHH 2.19 Hz). The components
of the AB system are broadened due to the weak
interaction of the protons with the phosphorus nucleus.
The methoxy protons resonate in the expected
region at δ 3.66 ppm, an integral intensity of this signal
confirms the presence of 12 protons. Unfortunately, we
failed to detect the coupling constant with the
phosphorus nucleus 3JHP due to the signal broadening.
cyclohexa-1,4-dienylphosphonates at δC
~
115–
120 ppm were not found. The appearance of intensive
signals shifted upfield to δC ~ 54–68 ppm indicated the
formation of the assumed adduct. Note that the 1H and
13C NMR spectra of the reaction mixtures contain the
signals of aromatic ring atoms indicating that the
minor oxidation product is the product of cyclohexa-
1,4-dienylphosphonate aromatization.
An intensive singlet signal in a strong field at δ
1.84 ppm corresponds to the protons of methyl groups
at the quaternary carbon atoms of the cyclohexene ring.
The 31P NMR spectrum of tetramethyl 4,5-
dibromo-4,5-dimethylcyclohex-1-ene-1,2-diylbisphos-
phonate IIa contains a singlet signal at δP 14.40 ppm.
The structure of dibromoderivatives IIa–IIf ob-
1
tained was confirmed by the H, 13C, and 31P NMR
spectra. Thus, in the 13C NMR spectrum of IIa shown
in Fig. 1 the carbon atoms C1 and C2 at the double
bond bound directly with the phosphorus atoms
resonate as a doublet signal at δC 137.81 ppm with a
Note that in the case of bromine addition to the
unsymmetrically substituted cyclohexa-1,4-dienyl-
phosphonates the formation of two or more stereo-
isomers was observed, which leads to the considerable
complication of the spectral pattern. In some cases it
was impossible to interpret the NMR spectra of the
adducts in detail.
1
large coupling constant JCP 190.8 Hz. The mag-
netically equivalent carbon atoms C3 and C6 give rise
to a triplet signal at δC 46.81 ppm (2JCP = 3JCP = 12.2 Hz).
The carbon atoms C4 and C5 bound with the bromine
atoms resonate as singlets of high intensity at δC
67.54 ppm.
In the case of the bromination of methyl-substituted
2-chloro-1,4-hexadienylphosphonate IIe existing as a
mixture of two regioisomers we also observed the
formation of two isomers, 4- and 5-methyl-substituted
4,5-dibromo-2-chlorohex-1-ene phosphonates, in a
ratio of 2:1.
A single intensive signal of two equivalent methyl
carbon atoms is shifted upfield to δC 8.29 ppm. The
carbon atoms of methoxy groups at the phosphorus
atoms appear as broad signal at δC 53.19 ppm, the
constant of the spin–spin coupling with the phosphorus
δC, ppm
δC, ppm
Fig. 1. 13C NMR spectrum of tetramethyl (4,5-dibromo-
4,5-dimethylcyclohex-1-ene-1,2-diyl)bisphosphonate (IIa).
Fig. 2. 1Н NMR spectrum of tetramethyl (4,5-dibromo-4,5-
dimethylcyclohex-1-ene-1,2-diyl)bisphosphonate (IIa).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 4 2012

654
TITOV et al.
EXPERIMENTAL
tetramethyl (4-methylcyclohexa-1,4-diene-1,2-diyl)bis-
phosphonate Ic. Н NMR spectrum, δ, ppm: 1.87 s
1
The NMR spectra were recorded on a Bruker AC-
200 [200.132 (1H), 50.328 (13C) and 81.014 MHz
(31P)], Bruker AC-400 [400.133 MHz (1H)], and Tesla
BS-497 (100 MHz) spectrometers, in the last case with
1H–{31P} double magnetic resonance experiments.
Hexamethyldisiloxane (HMDS) was used as an
(3Н, СН3), 3.05–3.35 m (4Н, СН2), 3.71 d (3Н,
3
3
СН3ОР, JHР 12.0 Hz), 3.82 d (3Н, СН3ОР, JHР 12.0
Hz), 4.51 br. s (1Н, СНBr). 13С NMR spectrum, δС,
2
ppm: 32.65 (СН3), 39.51 d (С3, JСР 12.2 Hz), 42.16 d
2
(С6, JСР 12.5 Hz), 53.12 br. s (СН3ОР), 54.79 d (С5,
3
3JСР 7.5 Hz), 61.25 d (С4, JСР 8.6 Hz), 140.74 d (С1,
1
1JСР 188.9 Hz), 140.61 d (С2, 1JСР 187.3 Hz). 31Р NMR
spectrum: δР 14.09 ppm.
internal reference for H NMR spectra, the chemical
shifts were recalculated to TMS. The phosphorus
chemical shifts were determined relative to external
85% phosphoric acid (Bruker AC-200) and trimethyl
phosphate (Tesla BS-497). The 13C NMR spectra were
referenced to the internal CDCl3 and recalculated to
TMS.
Dimethyl (4,5-dibromo-4,5-dimethyl-2-chloro-
cyclohex-1-en-1-yl)phosphonate (IId) was prepared
from dimethyl (4,5-dimethyl-2-chlorocyclohexa-1,4-
1
dien-1-yl)phosphonate Id. Н NMR spectrum, δ, ppm:
2
1.83 s and 1.85 s (6Н, СН3), 3.01 d (1Н, СН2СР, JHН
2
The organic solvents and reagents were purified
using standard laboratory techniques [4, 5].
19.6 Hz), 3.10 d (1Н, СН2СР, JHН 19.6 Hz), 3.08 d
2
2
(1Н, СН2, JHН 20.0 Hz), 3.31 d (1Н, СН2, JHН
20.0 Hz), 3.65 d. d (6Н, СН3ОР, JHР 11.2 Hz). 13С
3
General procedure for preparation of compounds
IIa–IIf. To a solution of the corresponding cyclohexa-
1,4-diene phosphonate I in dichloromethane was added
dropwise under cooling and stirring a solution of an
equimolar amount of Br2 in dichloromethane. After
complete addition, the reaction mixture was stirred for
1 h at room temperature. Then the solvent was distilled
off in a vacuum. The residue, a yellowish viscous oil,
is the target 4,5-dibromocyclohex-1-ene phosphonates
IIa–IIf.
NMR spectrum, δС, ppm: 29.10 and 28.86 (СН3),
2
3
46.14 d (С6, JСР 8.86 Hz), 51.97 d (С3, JСР 12.3 Hz),
52.53 (ОСН3), 68.25 (С5), 68.56 (С4), 120.84 d (С1,
1JСР 185.9 Hz), 140.45 (С2). 31Р NMR spectrum: δР
15.60 ppm.
Dimethyl
(4,5-dibromo-3-methyl-2-chloro-
cyclohex-1-en-1-yl)phosphonate (IIe) was prepared
from dimethyl (3-methyl-2-chlorocyclohexa-1,4-dien-
1-yl)phosphonate Ie. The first isomer, content 75%. 1Н
NMR spectrum, δ, ppm: 1.09 d (3Н, СН3, 3JHН 7.6 Hz),
2.88–3.30 m (1Н, СН; 2Н, СН2), 3.66 d (3Н, СН3ОР,
3JHР 6.8 Hz), 4.30–4.40 m (1Н, СНBr), 5.45–5.60 m
(1Н, СНBr). 13С NMR spectrum, δС, ppm: 22.44
Tetramethyl (4,5-dibromo-4,5-dimethylcyclohex-
1-ene-1,2-diyl)bisphosphonate (IIa) was prepared
from tetramethyl (4,5-dimethylcyclohexa-1,4-diene-1,2-
1
diyl)bisphosphonate Ia. Н NMR spectrum, δ, ppm:
3
2
(СН3), 35.34 d (С3, JСР 8.9 Hz), 43.50 d (С6, JСР
1.84 s (6Н, СН3), 3.12 d (2Н, СН2, 2JHН 19.2 Hz), 3.18
d (2Н, СН2, 2JHН 19.2 Hz), 3.66 br. s (12Н, ОСН3). 13С
NMR spectrum, δС, ppm: 29.08 (СН3), 46.81 t (С3,6,
2JСР 12.2 Hz), 53.40 br. s (СН3ОР), 67.54 (С4,5),
10.1 Hz), 52.63 (СН3ОР), 54.34 d (С5, JСР 11.4 Hz),
3
56.69 (С4), 125.47 d (С1, JСР 184.3 Hz), 139.54 (С2).
1
31Р NMR spectrum: δР 15.12 ppm. The second isomer,
1
content 25%. Н NMR spectrum, δ, ppm: 1.50 d (3Н,
1
137.81 d (С1,2, JСР 190.8 Hz). 31Р NMR spectrum: δР
3
СН3, JHН 7.6 Hz), 2.88–3.30 m (1Н, СН; 2Н, СН2),
14.39 ppm.
3
3.63 d (3Н, СН3ОР, JHР 6.5 Hz), 4.54–4.88 m (1Н,
СНBr), 5.45–5.60 m (1Н, СНBr). 13С NMR spectrum,
Tetramethyl (4,5-dibromo-3-methylcyclohex-1-ene-
1,2-diyl)bisphosphonate (IIb) was prepared from
tetramethyl (3-methylcyclohexa-1,4-diene-1,2-diyl)bis-
phosphonate Ib. 1Н NMR spectrum, δ, ppm: 1.10–1.70
m (3Н, СН3), 2.80–3.47 m (2Н, СН2; 1Н, СН; 3Н,
СН3), 3.74–3.90 m (12Н, СН3ОР), 4.46 br. s (1Н,
СНBr), 4.71 br. s (1Н, СНBr). The 13С and 31Р NMR
spectra contain the signals sets of the stereoisomers
mixture, which assignment was impossible.
δС, ppm: 22.44 (СН3), 36.16 d (С3, JСР 10.8 Hz),
3
42.12 d (С6, JСР 12.3 Hz), 44.81 (С4), 52.41 d
2
(СН3ОР, JСР 5.1 Hz), 53.42 d (С5, JСР 5.8 Hz),
126.81 d (С1, 1JСР 184.3 Hz), 142.57 (С2, 3JСР 10.1 Hz).
31Р NMR spectrum: δР 16.86 ppm.
2
3
Dimethyl
[4,5-dibromo-4(5)-methyl-2-chloro-
cyclohex-1-en-1-yl)phosphonate IIf was prepared
from dimethyl [4(5)-methyl-2-chlorocyclohexa-1,4-
dien-1-yl)phosphonate If as a mixture with isimer If'.
Tetramethyl (4,5-dibromo-4-methylcyclohex-1-
ene-1,2-diyl)bisphosphonate (IIc) was prepared from
1
Content of If 65%. Н NMR spectrum, δ, ppm: 1.90 s
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 4 2012

655
SYNTHESIS OF BROMINE-SUBSTITUTED CYCLOHEXENYLPHOSPHONATES
2
(3Н, СН3), 3.00 d (1Н, С3Н2, JНН 19.6 Hz), 3.07 d. d
61.87 d (С5, 3JСР 9.9 Hz), 120.18 d (С1, 1JСР 187.7 Hz),
139.98 (С2). 31Р NMR spectrum: δР 15.19 ppm.
(1Н, С6Н2, JНН 19.6, JНР 1.0 Hz), 3.22–3.55 m (1Н,
С3Н2, 2JНН 19.2 Hz), 3.72 d (6Н, СН3ОР, 3JHР 15.0 Hz),
4.46 br. s (1Н, С5НBr). 13С NMR spectrum, δС, ppm:
2
3
REFERNCES
32.67 (СН3), 38.57 d (С6, JСР 8.8 Hz), 47.52 d (С3,
2
1. Tverdomed, S.N., Dogadina, A.V., and Ionin, B.I., Zh.
Obshch. Khim., 2006, vol. 76, no. 6, p. 925.
2. Tverdomed, S.N., Röschenthaler, G.-V., Kalinovich, N.,
Lork, E., Dogadina, A.V., and Ionin, B.I., Tetrahedron,
2008, vol. 64, p. 5306.
3JСР 12.0 Hz), 52.68 br. s (СН3ОР), 53.41 d (С5, JСР
3
10.2 Hz), 62.30 (С4), 118.84 d (С1, JСР 187.6 Hz),
1
139.98 (С2). 31Р NMR spectrum: δР 15.47 ppm.
Dimethyl [4,5-dibromo-5-methyl-2-chlorocyclo-
hex-1-en-1-yl)phosphonate (IIf’), content 35%. Н
3. Titov, K.S., Zakharov, V.I., Krivchun, M.N., and
1
Ionin, B.I., Zh. Obshch. Khim., 2011, vol. 81, no. 3, p. 384.
NMR spectrum, δ, ppm: 1.91 s (3Н, СН3), 2.97–3.55
4. Titze, L. and Eicher, T., Preparative Organic
Chemistry, Moscow: Mir, 1999.
5. Preparativnaya organicheskaya khimiya (Preparative
Organic Chemistry), Vul’fson, N.S., Ed., Moscow:
Khimiya, 1964.
3
m (2Н, С3Н2; 2Н, С6Н2), 3.74 d (6Н, СН3ОР, JHР
13.8 Hz), 4.41 br. s (1Н, С5НBr). 13С NMR spectrum,
δС, ppm: 32.69 (СН3), 41.40 d (С6, 2JСР 7.2 Hz), 44.84
3
d (С3, JСР 11.9 Hz), 52.68 br.s (СН3ОР), 53.92 (С4),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 4 2012