Induced halogenation of alkyl cyclohexenyl ketones involving metal halides, hydrohalogenic acids, and hydrogen peroxide

Article abstract of DOI:10.1134/S107042800902002X

The induced halogenation and hydroxyhalogenation of alkyl cyclohexenyl ketones in a system [MHlg + HHlg or HHlg]-H₂O₂ or in NaOCl was performed and optimum reaction conditions were established. Under mild conditions the electrophilic addition of the halogen or the acid occurred at the multiple bond of the ring with the formation of the corresponding dihalo or hydroxyhalo derivatives of cycloaliphatic ketones. From the compounds obtained epoxy- and dioxyketones of aliphatic series were prepared. Chloro(bromo)hydrins of ketones from the alkylcyclohexane series and oxiranes based thereon are reactive compounds and can be employed as synthons in the organic synthesis.

Full text of DOI:10.1134/S107042800902002X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 2, pp. 166−172. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © O.A. Sadygov, Kh.M. Alimardanov, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 2, pp. 179−185.
Induced Halogenation of Alkyl Cyclohexenyl Ketones Involving
Metal Halides, Hydrohalogenic Acids, and Hydrogen Peroxide
O. A. Sadygov and Kh. M. Alimardanov
Mamedaliev Institute of Petrochemical Engineering, National Academy of Sciences of Azerbaidzhan,
Baku, Az1025 Azerbaidzhan
e-mail: hafizalimardanov@yahoo.com
Received May 23, 2008
Abstract—The induced halogenation and hydroxyhalogenation of alkyl cyclohexenyl ketones in a system [MHlg
+ HHlg or HHlg]–H2O2 or in NaOCl was performed and optimum reaction conditions were established. Under mild
conditions the electrophilic addition of the halogen or the acid occurred at the multiple bond of the ring with the
formation of the corresponding dihalo or hydroxyhalo derivatives of cycloaliphatic ketones. From the compounds
obtained epoxy- and dioxyketones of aliphatic series were prepared. Chloro(bromo)hydrins of ketones from the
alkylcyclohexane series and oxiranes based thereon are reactive compounds and can be employed as synthons in
the organic synthesis.
DOI: 10.1134/S107042800902002X
Halogen-substituted ketones and their derivatives are
convenient synthons for the synthesis of organic com-
pounds, and they are used in the production of insecticides,
antihelmintic agents and other biologically active com-
pounds [1–3]. These compounds can also be employed
as modifiers of epoxy resins [4] and antifreeze additives
to lubricants [5, 6].
aromatic compounds [13] and also of conjugated enyne
systems [14] results are reported of the halogenation and
hydroxyhalogenation of unsaturated ketones from the
cycloaliphatic series under the conditions of the formation
of Hlg2 and HOHlg in situ. We used as inducing system
[HHlg or MHlg + HHlg]–H2O2 (or NaOCl).
The synthesis of initial unsaturated ketones was
performed by acylation of cyclohexene with acid
chlorides of C2–C8 carboxylic acids by the known
procedure [15, 16]. The use in this reactions as catalyst
of highly dispersed AlCl3 and SnCl4 on a solid carrier
(HNa-mordenite) instead of usually applied soluble salts
(ZnCl2, AlCl3) made it possible to carry out the reaction
selectively at –10...0°C instead of –3...–25°C [16]
(Scheme 1).
The halogenation of various unsaturated compounds
is sufficiently thoroughly described in reviews [7–10] and
a monograph [11]. However the data on the induced
halogenation of unsaturated ketones, especially of cyclo-
aliphatic series, were practically absent.
In the present study in extension of the research on
the induced halogenation of aromatic [12] and alkenyl-
Scheme 1.
The composition and structure of obtained alkyl
SnCl4,
cyclohexenyl ketones Ia–Ig was established by elemental
HNa-mordenite,
1
5
analysis and IR and H NMR spectroscopy. In the IR
_10...0oC
2
1
.
.
.
spectra these compounds have common absorption bands
in the region 1660 and 1703 cm–1 characteristic of the
stretching vibrations of the C=O group of α,β-unsaturated
ketones. The bands in the region 752, 836, 965, 1634,
1640, 1654 cm–1 correspond to the C=C bonds of the
cyclohexene ring, andthe bands at 1377, 1420, 1445 cm–1,
.
6
3
+ RCOCl
C
4
O
R
Ià_Ig
R = CH3 (a), C2H5 (b), C3H7 (c), C4H9 (d), C5H11 (e), C6H13
(f), C7H15 (g).
166

INDUCED HALOGENATION OF ALKYL CYCLOHEXENYL KETONES
167
to the bending vibrations of groups CH2 and CH3 [17]. In
the H NMR spectra of compounds Ia–Ig appeared
Scheme 2.
HHlg_H2O2
1
-
8 13
O
( )
a triplet from the fragment =CH (6.71 ppm) and multiplets
at 1.65–1.96 ppm from the CH2 groups of the cyclo-
hexene ring. The singlet at 2.31 ppm in the spectrum of
ketone Ia belongs to the CH3 group of the acyl fragment.
With the growing length of the acyl residue the proton
signals of the terminal methyl group shift upfield (in the
1H NMR spectra of ketone Ib a doublet at 1.11 ppm, of
ketones Ic–Ig a triplet at 0.97 ppm). The protons of the
group CH2C=O in ketones Ib–Ig also give rise to a triplet
at 2.46 ppm [18, 19].
7C
CH3
H
or NaOCl
14
.
.
Hlg
6
5
1
H2O
3
C
4
2
H
O
R
H
OH
IVà_IVg, Và_Vg
Ià_Ig
X = Cl (II), Br (III).
Scheme 3.
It was established experimentally that alkyl cyclo-
hexenyl ketones in the presence of concentrated water
solutions of HHlg and H2O2 under the conditions of
induced addition of electrophilic reagents were easily
converted into 1.2-substituted dihalides IIa–IIg and IIIa–
IIIg (Scheme 2).
MX (HX)_H2O2
or NaOCl
5
X
-
8 13
6
3
( )
7
2
1
1
2
.
.
5
6
C
CH3
3
( )8 13
-
14
4
O
X
4
C
CH3
7
O
14
IIà_IIg, IIIà_IIIg
Hlg = Cl (IV), Br (V); R see Scheme 1.
The yield of dihaloketones IIa–IIg and IIIa–IIIg and
the selectivity of the process depend on the temperature,
the concentration of the water solutions of metal halides
or hydrohalogenic acids, and the intensity of stirring of
the reaction mixture. Inasmuch as the 1-(cyclohex-1-enyl)-
alkanones are sparingly soluble in water, the reaction
proceedes in a heterophase system on the phase boarder,
and in the stationary mode without vigorous stirring (the
rate of the agitator 500–600 rpm) the transfer of the
halogen from the water into the organic phase would be
significantly hampered leading to the decrease in the yield
of the products. The highest yield of 1-(1,2-dichlorocyclo-
hexyl)- and 1-(1,2-dibromocyclohexyl)alkanones was
obtained at 20–50°C and attained 73–94 and 72–89%
respectively. Raising the temperature from 50 to 70°C
resulted in decreased yield evidently due to the accelera-
tion of a side reaction, electrophilic substitution of hydro-
gen atoms in CH2 groups of the cyclohexane ring for
halogen atoms. With rising concentrations of the water
solutions of metal halides and hydrohalogenic acids (up
to 33% for NaCl, HCl and 45% for NaBr, HBr) the yields
of the target products increased up to 96 and 98% with
respect to the consumed halogen. At low concentrations
of salt and acid solutions (below 15%) the corresponding
chloro- and bromohydrins were obtained. Thus the
optimum conditions maximizing the yield of compounds
IIa–IIg and IIIa–IIIg are as follows: molar ratio Ia–
Ig–MHlg(HHlg)–H2O2 (or NaOCl) 1:2:2, concentration
of solutions of MHlg 25–30%, of hydrochloric and
hydrobromic acids 20–33 and 30–45% respectively,
temperature 20–40°C. With growing length of the alkyl
chain from CH3 to C7H15 the yields of the corresponding
dihalides diminished to 69–71%, apparently due to the
shielding of the double bond by the alkyl residues.
At the use of low concentrated solutions (HCl 10–
15%, HBr 6–8%) the corresponding products of hydroxy-
halogenation were obtained in sufficiently good yield
(Scheme 3).
The addition to the solutions of HCl and HBr up to 3–
7 wt % of MHlg also favored the increased yield of
hydroxyhalides.
The composition and structure of compounds IIa–IIg–
IVa–IVg were established from elemental analysis, IR
and H NMR spectra.
1
The hydroxyhalides and dihalides obtained from the
cyclohexenylalkanones easily underwent dehydro-
halogenation in the presence of powdered potassium
hydroxide (or sodium hydroxide) giving epoxides VIa–
VIg, and the latter were converted into trans-diols VIIa
and VIIb in 65–86% yield (Scheme 4).
The composition and structure of epoxides VIa–VIg
was confirmed by elemental analysis, IR and 1H NMR
spectra, and also by independent synthesis: by epoxidation
of cyclohexenylalkanones Ia–Ig with 30% dioxane
solution of H2O2 and CH3COOH in the presence of
chlorine-containing acidic cation-exchanger KU-2×8 or
KU-2×8p at the molar ratio substrate–H2O2–CH3COOH
1:1.2:0.5.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

SADYGOV, ALIMARDANOV
168
n 20 1.4882. Found, %: C 77.12; H 10.05. C8H12O.
Scheme 3.
CDalculated, %: C 77.42; H 9.68. Likewise were synthesiz-
R
ed compounds Ib–Ig.
Cold
20_22% NaOH
C=O
H
1-(Cyclohex-1-enyl)propan-1-one (Ib) was obtain-
ed from 21.5 g (0.24 mol) of propionyl chloride and
16.4 g (0.2 mol) of cyclohexene. Yield 19.2 g (70%),
bp 72–76°C (5 mm Hg), d420 0.9636, nD20 1.4871. Found,
%: C 78.12; H 10.36. C9H14O. Calculated, %: C 78.26;
H 10.14.
6
IVà_IVg
Và_Vg
5
1
Solid KÎÍ,
abs. (Et)2O, heating
3
+
4
6
2
O
H
H
VIà_VIg
OH
H
1-(Cyclohex-1-enyl)butan-1-one (Ic) was obtained
from 25.6 g (0.24 mol) of butanoyl chloride and 16.4 g
(0.2 mol) of cyclohexene. Yield 17.7 g (58%), bp 78–
81°C (5 mm Hg), d420 0.9428, nD20 1.4793. Found, %:
C 78.76; H 10.75. C10H16O. Calculated, %: C 78.95;
H 10.53.
7
C
R
H2O
KU-2
5
1
3
+
VIà, VIb
4
2
H
O
H
OH
VIIà, VIIb
R see Scheme 1.
1-(Cyclohex-1-enyl)pentan-1-one (Id) was obtain-
ed from 28.9 g (0.24 mol) of pentanoyl chloride and
16.4 g (0.2 mol) of cyclohexene. Yield 16.2 g (49%),
bp 86–89°C (5 mm Hg), d420 0.9338, nD20 1.4780. Found,
%: C 79.36; H 11.06. C11H18O. Calculated, %: C 79.52;
H 10.84.
EXPERIMENTAL
IR spectra of compounds synthesized were recorded
1
on a spectrophotometer UR-20, H NMR spectra, on
a spectrometer Bruker (300 MHz) from solutions in CCl4,
internal reference HMDS. Cyclohexene was obtained
by cyclohexanol dehydration followed by purification as
described in [20]. Monocarboxylic acid C2–C7 chlorides
were obtained by boiling the acids with the thionyl chloride
by the known procedure till the end of HCl evolution
(monitoring with litmus) [15]. The purity and isomeric
composition of compounds was estimated from TLC on
Silufol UV-254 plates (eluent benzene–ethyl ether, 3–5 :
1 v/v, development in iodine vapor) and from GLC on
a chromatograph LKhM-8M8-5, detector catharom-
eter, column 0.3×300 cm packed with Chromaton N-
AW DMCS impregnated with 5% silicone XΕ-60,
oven temperature 150°C, carrier gas helium, flow rate
40 ml/min.
1-(Cyclohex-1-enyl)hexan-1-one (Ie) was obtain-
ed from 32.3 g (0.24 mol) of hexanoyl chloride and 16.4 g
(0.2 mol) of cyclohexene.Yield 15.3 g (43%), bp 93–98°C
(5 mm Hg), d420 0.9248, nD20 1.4773. Found, %: C 78.86;
H 11.28. C12H20O. Calculated, %: C 80.0; H 11.11.
1-(Cyclohex-1-enyl)heptan-1-one (If) was
obtained from 35.5 g (0.24 mol) of a heptanoyl chloride
and 16.4 g (0.2 mol) of cyclohexene. Yield 14.3 g (36%),
bp 94–97°C (2 mm Hg), d420 0.9138, nD20 1.4722. Found,
%: C 79.32; H 11.16. C13H22O. Calculated, %: C 80.41;
H 11.34.
1-(Cyclohex-1-enyl)octan-1-one (Ig) was obtained
from 38.9 g (0.24 mol) of octanoyl chloride and 16.4 g
(0.2 mol) of cyclohexene. Yield 13.2 g (33%), bp 112–
115°C(2mmHg), d420 0.9012, nD20 1.4653.Found,%:C 81.18;
H 11.72. C14H24O. Calculated, %: C 80.71; H 11.54.
1-(Cyclohex-1-enyl)ethanone (Ia). To a solution
of 18.1 g (0.24 mol)of acetyl chloride in 30 ml of CCl4
at –15–0°C was added while stirring 6.3 g of SnCl4 or
AlCl3 dispersed on HNa-mordenite and afterwards
within 0.5 h was added 16.4 g (0.2 mol) of cyclohexene.
The reaction mixture was stirred for 60–90 min. Then
the content of the reactor was charged into a beaker
cooled with ice, the organic layer was separated and dried
with Na2SO4. A fraction of bp 60–90°C (1.5 mm Hg)
was distilled off, 2–3 h treated with sodium methylate,
then neutralized with 10% solution of hydrochloric acid,
washed with water, dried, and distilled in a vacuum.
Yield 20.2 g (81%), bp 65–67°C (5 mm Hg), d240 0.9703,
1-(1,2-Dichlorocyclohexyl)alkan-1-ones IIa–IIg.
To 22.5 g (0.2 mol) of 33% HCl was added 0.1 mol of
ketone Ia–Ig, then within 60 min was added 23 g
(0.2 mol) of 30% water solution of H2O2 or 124.2 g
(0.2 mol) of 18.5% solution of sodium hypochlorite (active
chlorine content 110 g-ion l−1). Then the temperature of
the reaction mixture was raised to 30–50°C, and the
stirring was continued for 4–5 h. On completion of the
reaction (H2O2 consumption was monitored by potassium
permanganate titration, NaOCl by iodometry [21]) the
organic layer was separated from the water phase,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

INDUCED HALOGENATION OF ALKYL CYCLOHEXENYL KETONES
169
washed, dried with anhydrous Na2SO4, and distilled in
a vacuum.
(72%), bp 151–154°C (5 mm Hg), d420 1.0562, nD20 1.4475.
Found, %: C 61.34; H 8.35; Cl 25.82. C14H24Cl2O.
Calculated, %: C 60.22; H 8.60; Cl 25.45.
1-(1,2-Dichlorocyclohexyl)ethanone (IIa) was
obtained from 6.2 g (0.05 mol) of ketone Ia. Yield 9.1 g
(94%), bp 90–92°C (5 mm Hg), d420 1.2073, nD20 1.4961.
IR spectrum, ν, cm–1: 2870 (CH), 1720 (C=O), 745, 710
Likewise were obtained compounds IIIa–IIIg. To
33.5 g (0.2 mol) of 46% HBr or 20.6 g (0.2 mol) of NaBr
or KBr was added 25 ml of H2O and 22.5 g (0.2 mol) of
30% water solution of H2O2 and 0.1 mol of ketone Ia–
Ig.
1
(C–Cl). H NMR spectrum, δ, ppm: 1.39–1.79 m and
1.49–2.04 m (CH2 of ring), 2.1 s (3H, CH3), 3.96 t (1H,
H2). Found, %: C 49.88; H 6.15; Cl 36.06. C8H12Cl2O.
Calculated, %: C 49.23; H 6.50; Cl 36.41.
1-(1,2-Dibromocyclohexyl)ethanone (IIIa) was
obtained from 12.4 g (0.1 mol) of ketone Ia. Yield 25.1 g
(89%), bp 115–118°C (2 mm Hg), d420 1.7634, nD20 1.5576.
IR spectrum, ν, cm–1: 2870 (CH), 1720, 1705 (C=O),
1654, 1634, 1445 (CH2, CH3), 750, 680, 590 (C–Br).
1H NMR spectrum, δ, ppm: 1.38 d (2H, C4H2), 1.48 d
(2H, C5H2), 1.76, 2.01 d (2H, C3H2), 2.02–2.26 d (2H,
C6H2), 2.11 s (3H, CH3), 4.01 t (1H, H2). Found, %:
C 33.27; H 4.76; Br 56.98. C8H12Br2O. Calculated, %:
C 33.8; H 4.22; Br 56.34.
1-(1,2-Dichlorocyclohexyl)propan-1-one (IIb)
was obtained from 6.9 g (0.05 mol) of ketone Ib. Yield
9.3 g (89%), bp 112–114°C (5 mm Hg), d420 1.1632, nD20
1.4882. IR spectrum, ν, cm–1: 2950 (CH), 1720 (C=O),
800, 745, 720 (C–Cl). 1H NMR spectrum, δ, ppm: 1.08 t
(3H, CH3), 2.5 d (2H, C8H2), 3.95 t (1H, H2). Found, %:
C 49.84; H 7.13; Cl 34.25. C9H14Cl2O. Calculated, %:
C 51.67; H 6.69; Cl 33.77.
1-(1,2-Dichlorocyclohexyl)butan-1-one (IIc) was
obtained from 7.6 g (0.05 mol) of ketone Ic. Yield 9.5 g
(85%), bp 114–117°C (4 mm Hg), d420 1.1437, nD20 1.4842.
IR spectrum, ν, cm–1: 2875 (CH), 1720 (C=O), 800, 745,
710 (C–Cl). 1H NMR spectrum, δ, ppm: 0.97 t (3H, CH3),
1.62 d (2H, C9H2), 2.46 t (2H, C8H2), 3.95 t (1H, H2).
Found, %: C 53.57; H 7.51; Cl 32.23. C10H16Cl2O.
Calculated, %: C 53.81; H 7.17; Cl 31.83.
1-(1,2-Dibromocyclohexyl)propan-1-one (IIIb)
was obtained from 13.8 g (0.1 mol) of ketone Ib. Yield
24.9 g (84%), bp 123–126°C (2 mm Hg), d420 1.7617,
nD20 1.5533. IR spectrum, ν, cm–1: 2950 (CH), 1720, 1705
(C=O), 750, 680, 590 (C–Br). 1H NMR spectrum, δ, ppm:
1.07 t (3H, CH3), 1.38 d (2H, C4H2), 1.48 d (2H, C5H2),
1.77–2.02 d (2H, C3H2), 2.02, 2.77 d (2H, C6H2), 2.50 d
(2H, C8H2), 4.02 t (1H, H2). Found, %: C 36.87; H 4.92;
Br 54.13. C9H14Br2O. Calculated, %: C 36.24; H 4.69;
Br 53.69.
1-(1,2-Dichlorocyclohexyl)pentan-1-one (IId)
was obtained from 8.3 g (0.05 mol) of ketone Id. Yield
9.7 g (82%), bp 123–125°C (4 mm Hg), d420 1.0956, nD20
1.4732. IR spectrum, ν, cm–1: 2960, 2880 (CH), 1720
(C=O), 800, 745, 710 (C–Cl). 1H NMR spectrum, δ, ppm:
0.96 t (3H, CH3), 1.34 d (2H, C10H2), 1.56 d (2H, C9H2),
2.46 d (2H, C8H2), 3.96 t (1H, H2). Found, %: C 56.82;
H 7.89; Cl 30.42. C11H18Cl2O. Calculated, %: C 55.69;
H 7.59; Cl 29.95. Identical spectral data were obtained
for compounds IIe–IIg.
1-(1,2-Dibromocyclohexyl)butan-1-one (IIIc) was
obtained from 15.2 g (0.1 mol) of ketone Ic. Yield 25.6 g
(82%), bp 128–132°C (2 mm Hg), d420 1.7582, nD20 1.5465.
IR spectrum, ν, cm–1: 2875 (CH), 1720, 1705 (C=O),
750, 680, 590 (C–Br). 1H NMR spectrum, δ, ppm: 0.97 t
(3H, CH3), 1.62 q (2H, C9H2), 2.85 t (2H, C8H2), 4.01 t
(1H, H2). Found, %: C 39.12; H 5.46; Br 52.32.
C10H16Br2O. Calculated, %: C 38.46; H 5.13; Br 51.28.
1-(1,2-Dichlorocyclohexyl)hexan-1-one (IIe) was
obtained from 9 g (0.05 mol) of ketone Ie. Yield 9.4 g
(75%), bp 139–142°C (5 mm Hg), d420 1.0715, nD20 1.4672.
Found, %: C 57.71; H 7.92; Cl 29.10. C12H20Cl2O.
Calculated, %: C 57.37; H 7.96; Cl 28.28.
1-(1,2-Dibromocyclohexyl)pentan-1-one (IIId)
was obtained from 16.6 g (0.1 mol) of ketone Id. Yield
24.8 g (76%), bp 134–136°C (2 mm Hg), d420 1.7526,
nD20 1.5436. 1H NMR spectrum, δ, ppm: 0.97 t (3H, CH3),
1.34 q (2H, C10H2), 1.58 q (2H, C9H2), 2.46 t (2H, C8H2),
4.01 t (1H, H2). Found, %: C 40.51; H 5.96; Br 49.86.
C11H18Br2O. Calculated, %: C 40.49; H 5.52; Br 49.08.
1-(1,2-Dichlorocyclohexyl)heptan-1-one (IIf) was
obtained from 9.7 g (0.05 mol) of ketone If. Yield 9.8 g
(74%), bp 145–148°C (5 mm Hg), d420 1.0623, nD20 1.4583.
Found, %: C 59.26; H 8.32; Cl 26.83. C13H22Cl2O.
Calculated, %: C 58.87; H 8.30; Cl 26.79.
1-(1,2-Dibromocyclohexyl)hexan-1-one (IIIe)
was obtained from 18 g (0.1 mol) of ketone Ie. Yield
25.4 g (75%), bp 138–139°C (2 mm Hg), d420 1.7174,
nD20 1.5412. 1H NMR spectrum, δ, ppm: 0.97 t (3H, CH3),
1.34 q (2H, C11H2), 1.29 q (2H, C10H2), 1.56 q (2H,
1-(1,2-Dichlorocyclohexyl)octan-1-one (IIg) was
obtained from 10.2 g (0.05 mol) of ketone Ig. Yield 10 g
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

SADYGOV, ALIMARDANOV
170
C9H2), 2.46 t (2H, C8H2), 4.02 t (1H, H2). Found, %:
C 42.88; H 6.12; Br 48.15. C12H20Br2O. Calculated, %:
C 42.35; H 5.88; Br 47.06.
spectrum, δ, ppm: 1.38–2.05 m (8H, CH2 of ring), 2.10 s
(3H, CH3), 3.71 t (1H, H2), 4.81 ψ.C (1H, OH). Found,
%: C 54.83; H 8.15; Cl 20.41. C8H13ClO2. Calculated,
%: C 54.39; H 7.37; Cl 20.11.
1-(1,2-Dibromocyclohexyl)heptan-1-one (IIIf)
was obtained from 19.4 g (0.1 mol) of ketone If. Yield
26.1 g (74%), bp 142–145°C (2 mm Hg), d420 1.6883,
nD20 1.5485. Found, %: C 46.38; H 7.17; Br 44.52.
C14H24Br2O. Calculated, %: C 45.65; H 6.52; Br 43.43.
1-[1(2)-Hydroxy-2(1)-chlorocyclohexyl]propan-
1-one (IVb) was obtained from 6.9 g (0.05 mol) of ketone
Ib. Yield 7.4 g (78%), bp 116–118°C (11 mm Hg), d420
1.2335, nD20 1.5367. IR spectrum, ν, cm–1: 3625, 1100 (C–
OH), 2870 (CH), 1720 (C=O), 830, 745 (C–Cl). 1H NMR
spectrum, δ, ppm: 1.07 d (3H, CH3), 2.48 d (2H, C8H2),
3.71 t (1H, H2), 4.81 br.s (1H, OH). Found, %: C 57.26;
H 7.36; Cl 19.25. C9H15ClO2. Calculated, %: C 56.69; H
7.87; Cl 18.64.
1-(1,2-Dibromocyclohexyl)octan-1-one (IIIg) was
obtained from 20.8 g (0.1 mol) of ketone Ig. Yield 26.6 g
(73%), bp 146–149°C (2 mm Hg), d420 1.6748, nD20 1.5436.
Found, %: C 46.38; H 6.97; Br 43.82. C14H24Br2O.
Calculated, %: C 45.65; H 6.52; Br 43.43.
1-[1(2)-Hydroxy-2(1)-chlorocyclohexyl]butan-1-
one (IVc) was obtained from 7.2 g (0.05 mol) of ketone
Ic. Yield 7.8 g (76%), bp 120–122°C (10 mm Hg), d420
1.2286, nD20 1.5346. Found, %: C 57.49; H 8.62; Cl 17.82.
C10H17ClO2. Calculated, %: C 58.68; H 8.31; Cl 17.40.
A mixture of isomers 1-[1(2)-hydroxy-2(1)-
chlorocyclohexyl]- and [1(2)-bromo-2(1)-hydroxy-
cyclohexyl]alkan-1-ones. Into a flask at desired
temperature was charged 0.15–0.2 mol of 6–8% water
solution of HBr or 6–10% solution of HCl and 0.1 mol of
ketone Ia–Ig.At vigorous stirring of the reaction mixture
was added 0.15–0.22 mol of 26–30% water solution of
hydrogen peroxide at a rate 10 g per hour or 124.2 g
(0.2 mol) of 18.5% solution of sodium hypochlorite (active
chlorine content 110 g-ion l−1). The mixture was stirred
for 5–7 h. The completion of reaction was monitored by
permanganatometric or iodometric titration [21]. After
total consumption of the oxidant the obtained chloro- and
bromohydrins were further used in preparation of the
corresponding epoxycyclohexylalkanones by adding into
the reaction mixture potassium hydroxide. In order to
establish the structure and physicochemical constants of
the halohydrins the organic layer was separated from
the water layer. The reaction products were extracted
from the water layer into ethyl ether (2 × 50 ml). The
combined organic solutions were neutralized with 10%
solution of Na2CO3, dried with magnesium sulfate, and
after distilling off the ether we isolated a mixture of
halohydrins IVa–IVg and Va–Vg. According to the data
of GLC, TLC, and IR spectroscopy the obtained
1-[chloro(bromo)hydroxy-cyclohexyl]alkan-1-ones are
composed of two cis-isomers: 85–92% of 1-(2-hydroxy-
1-chlorocyclohexyl)- and 6–12% of 1-(1-hydroxy-2-
chlorocyclohexyl)alkan-1-ones, or 73–82% of 1-bromo-
2-hydroxycyclohexyl)- and 17–23% of 1-(2-bromo-1-
hydroxycyclohexyl)alkan-1-ones.
1-[1(2)-Hydroxy-2(1)-chlorocyclohexyl]pentan-
1-one (IVd) was obtained from 8.3 g (0.05 mol) of ketone
Id. Yield 8.1 g (75%), bp 125–126°C (10 mm Hg), d420
1.2258, nD20 1.5278. Found, %: C 61.35; H 8.92; Cl 16.75.
C11H19ClO2. Calculated, %: C 60.41; H 8.69; Cl 16.25.
1-[1(2)-Hydroxy-2(1)-chlorocyclohexyl]hexan-1-
one (IVe) was obtained from 9 g (0.05 mol) of ketone
Ie. Yield 8.4 g (72%), bp 128–130°C (10 mm Hg), d420
1.2232, nD20 1.5256. Found, %: C 62.23; H 9.28; Cl 15.86.
C12H21ClO2. Calculated, %: C 61.95; H 9.03; Cl 15.27.
1-[1(2)-Hydroxy-2(1)-chlorocyclohexyl]heptan-
1-one (IVf) was obtained from 9.7 g (0.05 mol) of ketone
If. Yield 8.7 g (70%), bp 132–134°C (8 mm Hg), d420
1.2215, nD20 1.5194. Found, %: C 63.78; H 9.76; Cl 14.96.
C13H23ClO2. Calculated, %: C 63.29; H 9.33; Cl 14.40.
1-[1(2)-Hydroxy-2(1)-chlorocyclohexyl]octan-1-
one (IVg) was obtained from 10.4 g (0.05 mol) of ketone
Ig. Yield 8.9 g (69%), bp 136–138°C (5 mm Hg), d420
1.2208, nD20 1.5167. Found, %: C 65.18; H 9.84; Cl 14.18.
C14H25ClO2. Calculated, %: C 64.49; H 9.57; Cl 13.63.
1-[1(2)-Hydroxy-2(1)-bromocyclohexyl]-
ethanone (Va) was obtained from 12.4 g (0.1 mol) of
ketone Ia. Yield 17.3 g (75%), bp 86–88°C (5 mm Hg),
d420 1.4295, nD20 1.5204. IR spectrum, ν, cm–1: 3615, 1410,
1
1380 (OH), 1720 (C=O), 640, 623 (C–Br). H NMR
spectrum, δ, ppm: 2.10 s (3H, CH3), 3.28 t (1H, H2), 4.82
C (1H, OH). Found, %: C 43.81; H 6.26; Br 36.84.
C8H13BrO2. Calculated, %: C 43.44; H 5.88; Br 36.2.
1-[1(2)-Hydroxy-2(1)-chlorocyclohexyl]ethanone
(IVa) was obtained from 6.2 g (0.05 mol) of ketone Ia.
Yield 7.2 g (82%), bp 112–114°C (11 mm Hg), d420 1.2368,
nD20 1.5382. IR spectrum, ν, cm–1: 3625, 1100 (C–OH),
2870 (CH), 1720 (C=O), 830, 745, 660 (C–Cl). 1H NMR
1-[1(2)-Hydroxy-2(1)-bromocyclohexyl]propan-
1-one (Vb) was obtained from 13.8 g (0.1 mol) of ketone
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

INDUCED HALOGENATION OF ALKYL CYCLOHEXENYL KETONES
171
Ib. Yield 17.3 g (74%), bp 90–91°C (5 mm Hg), d420
1.4264, nD20 1.5296. IR spectrum, ν, cm–1: 3615, 1410,
spectrum, δ, ppm: 2.10 s (3H, CH3), 3.10 t (1H, H2).
Found, %: C 68.85; H 8.82. C8H12O2. Calculated, %:
C 68.57; H 8.57.
1
1380 (OH), 1720 (C=O), 648, 620 (C–Br). H NMR
spectrum, δ, ppm: 1.08 t (3H, CH3), 2.51 q (2H, C8H2),
3.81 t (1H, H2), 4.81 br.s (1H, OH). Found, %: C 46.43;
H 6.91; Br 34.72. C9H15BrO2. Calculated, %: C 45.96;
H 6.38; Br 34.0.
1-(7-Oxabicyclo[4.1.0]hept-1-yl)propan-1-one
(VIb) was obtained from 9.5 g (0.05 mol) of enone IVb
or 13.3 g (0.05 mol) of compound Vb. Yield 6.1 g (80%)
from IVb, 13.3 g (86%) from Vb, bp 90–91°C (10 mm
Hg), d420 1.0946, nD20 1.4682. IR spectrum, ν, cm–1: 1730,
1722, 1704 (C=O), 1260, 1250, 920, 863 (epoxyd).
1H NMR spectrum, δ, ppm: 1.07 t (3H, CH3), 2.48 q
(2H, CH2CO), 3.10 t (1H, H2). Found, %: C 70.84;
H 9.32. C9H14O2. Calculated, %: C 70.13; H 9.09.
1-[1(2)-Bromo-2(1)-hydroxycyclohexyl]-butan-1-
one (Vc) was obtained from 15.2 g (0.1 mol) of ketone
Ic. Yield 17.6 g (71%), bp 95–96°C (5 mm Hg), d420
1.4186, nD20 1.5237. Found, %: C 48.73; H 7.26; Br 33.16.
C10H17BrO2. Calculated, %: C 48.19; H 6.83; Br 32.13.
1-(7-Oxabicyclo[4.1.0]hept-1-yl)butan-1-one
(VIc) was obtained from 10.5 g (0.05 mol) of enone IVc
or 12.5 g (0.05 mol) of enone Vc. Yield 6.4 g (80%) from
IVc, 14.3 g (85%) from Vc, bp 97–98°C (10 mm Hg),
d240 1.0946, nD20 1.4686. IR spectrum, ν, cm–1: 1730, 1722,
1704 (C=O), 1260, 1250, 920, 863 (epoxyd). 1H NMR
spectrum, δ, ppm: 3.10 t (1H, H2), 2.46 t (2H, C8H2),
1.62 q (2H, C9H2), 0.97 q (3H, CH3). Found, %: C 71.86;
H 9.86. C10H16O2. Calculated, %: C 71.43; H 9.52.
1-[1(2)-Bromo-2(1)-hydroxycyclohexyl]pentan-
1-one (Vd) was obtained from 8.3 g (0.05 mol) of ketone
Id. Yield 9.2 g (70%), bp 101–107°C (5 mm Hg), d420
1.3962, nD20 1.5218. Found, %: C 50.61; H 7.56; Br 30.71.
C11H19BrO2. Calculated, %: C 50.19; H 7.22; Br 30.42.
1-[1(2)-Bromo-2(1)-hydroxycyclohexyl]hexan-1-
one (Ve) was obtained from 9 g (0.05 mol) of ketone Ie.
Yield 9.6 g (69%), bp 105–108°C (5 mm Hg), d420 1.3884,
nD20 1.5206. Found, %: C 52.63; H 7.82; Br 29.25.
C12H21BrO2. Calculated, %: C 51.98; H 7.58; Br 28.88.
1-(7-Oxabicyclo[4.1.0]hept-1-yl)pentan-1-one
(VId) was obtained from 10.9 g (0.05 mol) of enone IVd
or 13.2 g (0.05 mol) of enone Vd. Yield 6.7 g (73%) from
IVd, 15 g (83%) from Vd, bp 105–106°C (10 mm Hg),
d420 0.9865, nD20 1.4663. IR spectrum, ν, cm–1: 1730, 1722,
1704 (C=O), 1260, 1250, 920 (epoxyd). 1H NMR spec-
trum, δ, ppm: 3.09 t (H2), 2.48 t (2H, C8H2), 1.62 q (2H,
C9H2), 1.57 t (2H, C10H2), 1.34 q (2H, C11H2), 0.97 t
(3H, CH3). Found, %: C 72.85; H 9.23. C11H18O2.
Calculated, %: C 72.53; H 8.89. Identical spectral
characteristics were obtained for compounds VIe–VIg
1-[1(2)-Bromo-2(1)-hydroxycyclohexyl]heptan-
1-one (Vf) was obtained from 9.7 g (0.05 mol) of ketone
If. Yield 10 g (68%), bp 110–112°C (5 mm Hg). Found,
%: C 54.13; H 8.15; Br 28.26. C13H23BrO2. Calculated,
%: C 53.61; H 7.9; Br 27.49.
1-[1(2)-Bromo-2(1)-hydroxycyclohexyl]octan-1-
one (Vg) was obtained from 10.4 g (0.05 mol) of ketone
Ig. Yield 10.1 g (67%), bp 115–116°C (3 mm Hg). Found,
%: C 56.13; H 8.74; Br 26.98. C14H25BrO2. Calculated,
%: C 55.08; H 8.2; Br 26.23.
1-(7-Oxabicyclo[4.1.0]hept-1-yl)hexan-1-one
(VIe) was obtained from 11.6 g (0.05 mol) of enone IVe
or 13.8 g (0.05 mol) of enone Ve. Yield 6.7 g (74%) from
IVe, 15.8 g (81%) from Ve, bp 112–113°C (10 mm Hg),
d420 0.9736, nD20 1.4642. Found, %: C 73.85; H 10.6.
C12H20O2. Calculated, %: C 73.47; H 10.2.
1,2-Epoxycyclohexenylalkanones VIa–VIg. To
0.05 mol of a solution of compounds IVa–IVg and Va–
Vg in 60 ml of ether cooled to 5–10°C was added at
vigorous stirring 8.4 g (0.15 mol) of powdered potassium
hydroxide. The reaction mixture was stirred for 3 h at
18–25°C. After the common workup and removal of
solvents products Va–Vg were isolated by a vacuum
distillation. At the use of 28–30 g of 22% cooled solution
of sodium hydroxide and after stirring the reaction mixture
for 4–5 h we also obtained the corresponding epoxides.
1-(7-Oxabicyclo[4.1.0]hept-1-yl)heptan-1-one
(VIf) was obtained from 12.3 g (0.05 mol) of enone IVf
or 14.6 g (0.05 mol) of enone Vf. Yield 7.2 g (68%) from
IVf, 16.7 g (80%) from Vf, bp 120–121°C (10 mm Hg),
d420 0.9684, nD20 1.4625. Found, %: C 74.72; H 10.87.
C13H22O2. Calculated, %: C 74.29; H 10.48.
1-(7-Oxabicyclo[4.1.0]hept-1-yl)ethanone (VIa)
was obtained from 8.8 g (0.05 mol) of compound IVa or
11 g (0.05 mol) of compound Va. Yield 5.8 g (83%) from
IVa, 12.5 g (90%) from Va, bp 83–84°C (10 mm Hg),
d420 1.1083, nD20 1.4812. IR spectrum, ν, cm–1: 1730, 1722,
1704 (C=O), 1260, 1250, 920, 863 (epoxyd). 1H NMR
1-(7-Oxabicyclo[4.1.0]hept-1-yl)octan-1-one
(VIg) was obtained from 13 g (0.05 mol) of enone IVg
or 15.2 g (0.05 mol) of enone Vg. Yield 7.1 g (77%) from
IVg, 17.5 g (78%) from Vg, bp 128–129°C (10 mm Hg),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

SADYGOV, ALIMARDANOV
172
d420 0.9616, nD20 1.4584. Found, %: C 75.62; H 11.42.
Chem. Abstr., 1967, vol. 76, 21817.
6. Plavsic, V., Kveder, S., and Iskric, S., Groat. Chim. Acta,
1972, vol. 44, p. 303.
7. Boguslavskaya, L.S., Usp. Khim., 1972, vol. 51, p. 1591.
8. Sergeev, G.B. and Leenson, I.A., Usp. Khim., 1972, vol. 51,
p. 1566.
9. Sergeev, G.B., Serguchev, Yu.A., and Smirnov, V.V., Usp.
Khim., 1973, vol. 52, p. 1545.
10. Mironov, V.A., Fedorovich, A.D., andAkhrem,A.A., Usp.
Khim., 1983, vol. 51, p. 101.
C14H24O2. Calculated, %: C 75.0; H 10.71.
Diols VIIa and VIIb. To 7 g (0.05 mol) of compound
VIa or VIb was added 9 g (0.05 mol) of water and 3.5 g
of KU-2×8. The mixture obtained was stirred for 4 h at
50–60°C, further by extraction with ethyl acetate from
a saturated solution of K2CO3, by recrystallization from
a mixture hexane–EtOAc, 7:3, or from CCl4 along
procedure [22] the corresponding diols were isolated.
1-(1,2-Dihydroxycyclohexyl)ethanone (VIIa).
Yield 6.7 g (84%), mp 105–108°C, Rf 0.68 (hexane–
EtOAc, 7:3). IR spectrum, ν, cm–1: 3625, 3615, 1100,
974, 918 (OH), 1723 (C=O). 1H NMR spectrum, δ, ppm:
3.48 t (1H, H2), 2.1 br.s (C1OH), 4.81 br.s (C2OH), 2.1 s
(3H, CH3). Found, %: C 61.34; H 9.23. C8H14O3.
Calculated, %: C 60.76; H 8.86.
11. De la Mare, P. B. D., and Bolton, R., Electrophilic Additions
to Unsaturated Systems,Amsterdam: Elsevier, 1966 New
York: Elsevier, 1982, 2 ed.
12. Sadygov, O.A.,Alimardanov, Kh.M., Chalabiev, Ch.A., Zh.
Org. Khim., 2005, 41, 1665; Neftekhimiya., 2006, vol. 46, p.
144; Zh. Prikl. Khim., 2006, vol. 79, p. 959.
13. Sadygov, O.A. and Alimardanov, Kh.M., Zh. Org. Khim.,
2007, vol. 43, p. 1664.
1-(1,2-Dihydroxycyclohexyl)propan-1-one
(VIIb). Yield 6.9 g (80%), mp 110–112°C, Rf 0.68
(hexane–EtOAc, 7:3). IR spectrum, ν, cm–1: 3625, 3615,
1100, 974, 918 (OH), 1723 (C=O). 1H NMR spectrum,
δ, ppm: 3.48 t (1H, H2), 2.0 br.s (1H, C1OH), 4.81 br.s
(1H, C2OH), 2.49 d (2H, C8H2), 1.07 d (3H, CH3). Found,
%: C 63.25; H 9.64. C9H16O3. Calculated, %: C 62.79;
H 9.30.
14. Veliev, M.G., Sadygov, O.A., Alimardanov, Kh.M., and
Shatirova, M.I., Zh. Org. Khim., 2007, vol. 43, p. 1609.
15. Becker, H., Organicum, New York: Pergamon press, 1973.
16. Pishnamaz-zade, B.F. and Guseinov, I.A., Az. Neftyanoe
Khozyaistvo, 1969, no. 1, p. 30.
17. Bellamy, L.J., The Infra-red Spectra of Complex Molecules,
London: Methuen, 1958.
18. Ionin, B.I. and Ershov, B.A., YaMR spektry v organi-
cheskoi khimii (NMR Speactra in Organic Chemistry),
Leningrad: Khimiya, 1967, p. 222.
REFERENCES
19. Gordon, A.J. and Ford, R.A., The Chemist’s Companion,
NewYork:Wiley, 1972.
20. Golodnikov, T.V. and Mandel’shtam, T.V., Praktikum po
organicheskomu sintezu (Practicum on Organic
Synthesis), Leningrad, 1976.
21. Babko, A.K. and Pyatnitskii, I.V., Kolichestvennyi analiz
(Qualitative Analysis), Moscow: Vysshaya Shkola, 1962,
p. 508.
22. Malinovskii, M.S., Okisi olefinov i ikh proizvodnye
(Oxides of Olefines and Their Derivatives), Moscow:
Goskhimizdat, 1961, p. 521.
1. Pilgram, K., Kendall, and Hass, D., J. Med. Chem., 1975,
vol. 18, p. 1204.
2. Mirsakova, A.N., Levkovskaya, G.G., Lidina, P.V., and
Voronkov, M.G., Khim.-Farm. Zh., 1977, no. 3, 74.
3. Kalyagina, G.F., Glazunova, N.I., Meshcheryakov, V.M.,
Gavrilov, L.D., and Vereshchagin, L.I., Khim.-Farm. Zh.,
1981, no. 2, p. 46.
4. Pishnamazzade, B.F., Guseinov, I.A., Nagieva, Sh.R., and
Khalilov, Kh.D., USSR Inventor’s Certificate 690003, 1978;
SSSR Byull. Izobr., 1979, no. 37.
5. Aron-Samuel, J.M.D., French Patent 1453808(A), 1966;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009