Intermolecular dehydration of alcohols by the action of copper compounds activated with carbon tetrabromide. synthesis of ethers

Article abstract of DOI:10.1134/S1070428012090072

Copper compounds of the general formula C_uX_n (X = Cl, Br, I, acac, OAc, C₇H₄O₃, C₇H ₅O₂; n = 1, 2) activated by carbon tetrabromide catalyzed intermolecular dehydration of primary and secondary alcohols with formation of the corresponding ethers.

Full text of DOI:10.1134/S1070428012090072

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 9, pp. 1191–1196. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © R.I. Khusnutdinov, A.R. Bayguzina, L.I. Gimaletdinova, U.M. Dzhemilev, 2012, published in Zhurnal Organicheskoi Khimii, 2012,
Vol. 48, No. 9, pp. 1192–1197.
Intermolecular Dehydration of Alcohols by the Action
of Copper Compounds Activated with Carbon Tetrabromide.
Synthesis of Ethers
R. I. Khusnutdinov, A. R. Bayguzina, L. I. Gimaletdinova, and U. M. Dzhemilev
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
Received March 3, 2012
Abstract—Copper compounds of the general formula CuXn (X = Cl, Br, I, acac, OAc, C7H4O3, C7H5O2;
n = 1, 2) activated by carbon tetrabromide catalyzed intermolecular dehydration of primary and secondary
alcohols with formation of the corresponding ethers.
DOI: 10.1134/S1070428012090072
Ethers are used as solvents, fuel additives, cos-
metics, and detergents [1–3]. The commonest proce-
dures for the preparation of ethers are based on the
Williamson reaction, intermolecular dehydration of al-
cohols, and addition of alcohols to alkenes; the two
latter reactions require acid catalysis [2, 4–9]. Syn-
thesis of ethers via intermolecular dehydration in the
presence of mineral acids or other acid catalysts is
possible only from lower alcohols; higher alcohols
undergo intramolecular dehydration with formation of
olefins which polymerize under these conditions.
Furthermore, the use of acid catalysts requires special
corrosion-resistant equipment and considerably hinders
the isolation procedure.
bromide (III). The yield of II reached 23% when the
amount of CuBr2 was raised to 5%. These findings
prompted us to test a large number of copper(I) and
copper(II) compounds for catalytic activity in inter-
molecular dehydration of alcohols. However, none of
the following copper compounds displayed catalytic
activity: CuCl, CuBr, CuI, CuCl2·2H2O, Cu(OAc)2,
Cu(acac)2, Cu(C7H5O2)2·2H2O, Cu(C7H8O6)2.
Taking into account importance of the problem
concerning synthesis of ethers and accessibility of cop-
per compounds, we tried to enhance catalytic activity
of the above copper compounds in intermolecular
dehydration of alcohols by selecting promoting dopes.
As the latter we examined conventional activating
ligands such as alkyl- and arylphosphines and nitro-
gen-containing compounds (amines, nitriles, pyridine
and its derivatives). However, successful results were
achieved with the use of halomethanes, the best of
which was carbon tetrabromide; the most efficient
catalytic system consisted of Cu(acac)2 and CBr4 at
a molar ratio of 1:5. This catalytic system ensured
95% yield of dicyclohexyl ether (II) in 8 h at 150°C
(Scheme 1). The activating effect of CBr4 (which is
converted into bromoform) was also observed toward
Reactions of alkenes with alcohols are charac-
terized by low selectivity and are accompanied by side
processes involving oligomerization and polymeriza-
tion of alkenes. Insofar as Williamson reaction utilizes
stoichiometric amounts of metallic sodium and sodium
hydride as reagents, it is only of preparative value.
The goal of the present work was to find efficient
catalysts for intermolecular dehydration of alcohols on
the basis of copper compounds. Using copper(II)
bromide as an example we found that intermolecular
dehydration of alcohols in the presence of copper
compounds is possible in principle. By heating cyclo-
hexanol (I) in the presence of 1% of CuBr2 (150°C,
8 h) we obtained 5% of dicyclohexyl ether (II). The
reaction mixture also contained traces of cyclohexyl
Scheme 1.
Cu(acac)2–CBr4
150°C, 8 h
OH
O
95%
I
II
1191

KHUSNUTDINOV et al.
1192
Table 1. Intermolecular dehydration of cyclohexanol (I) in the presence of different copper compounds and halomethanesa
Yield, %
Molar ratio catalyst–halo-
methane–alcohol
Conversion
of I, %
Copper compound Halomethane
II
III
IV
CuBr
–
5:0:100
1:5:100
1:0:100
5:0:100
1:5:100
1:0:100
1:1:100
1:5:100
1:20:100
1:30:100
1:5:100
1:5:100
1:10:100
1:5:100
1:10:100
1:5:100
1:5:100
1:5:100
1:5:100
1:5:100
1:5:100
00
65
00
44
05
23
44
00
12
95
38
20
31
10
13
28
11
44
39
39
37
46
42
00
21
01
05
14
00
01
03
22
30
20
88
66
48
77
20
26
15
14
05
11
0
0
CuBr
CBr4
–
CuBr2
06
0
CuBr2
–
28
0
CuBr2
CBr4
–
58
0
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
CuCl
00
0
CBr4
CBr4
CBr4
CBr4
CHBr3
CBrCl3
CBrCl3
CCl4
CCl4
CBr4
CBr4
CBr4
CBr4
CBr4
CBr4
15
2
1000
67
2
7
1000
55
500
4
1000
81
2
2
79
3
89
1
64
0
CuCl2·2H2O
CuI
65
0
64
0
Cu(OAc)2
Cu(C7H8O6)2
Cu(C7H5O2)2·2H2O
56
5
51
0
53
0
a
Temperature 150°C, reaction time 8 h.
other copper compounds (Table 1). Replacement of
CBr4 by other halomethanes, such as CHBr3, CBrCl3,
and CCl4 resulted in lower selectivity and reduced
yield of II (Table 1).
Using dehydration of cyclohexanol (I) as model
reaction we determined the optimal concentrations of
Cu(acac)2, CBr4, and substrate and optimal conditions.
Higher concentration of CBr4 [Cu(acac)2–CBr4–I
1:(10–100):100] favored side processes, in particular
substitutive bromination and oxidation of cyclohexanol
to cyclohexanone (IV) (Scheme 2). At an equimolar
ratio of Cu(acac)2 and CBr4 the conversion of I was as
low as 15%.
by-products, we presumed that the reaction follows
Scheme 3. The process begins with catalytic reaction
of CBr4 with alcohol I, which leads to the formation of
bromoform and cyclohexyl hypobromite (V) at a con-
centration of 1.5 mg/ml (according to the iodometric
titration data). Unstable hypobromite V decomposes
via elimination of HBr (20.34 mg/ml, mercurimetric
titration) to give cyclohexanone IV. The liberated
hydrogen bromide catalyzes [either alone or as the
complex Cu(acac)2·HBr] intermolecular dehydration
of I with formation of ether II.
The proposed mechanism was checked by carrying
out experiments with specially added HBr to a concen-
tration of 2%. This concentration is comparable with
that of HBr generated in situ by reaction of I with CBr4
Taking into account the formation of bromoform,
cyclohexyl bromide (III), and cyclohexanone (IV) as
Scheme 2.
Cu(acac)2–CBr4
150°C, 8 h
OH
O
Br
O
+
+
I
II
III
IV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

INTERMOLECULAR DEHYDRATION OF ALCOHOLS
1193
Scheme 3.
OBr
Br
O
Cu(acac)2–CBr4 (1:1)
–CHBr3
OH
–HBr
O
HBr or Cu(acac)2–HBr
–H2O
V
IV
HBr
II
I
–H2O
III
Scheme 4.
2% Cu(acac)2–HBr
150°C, 8 h
O
Br
O
+
+
+
OH
II
III
III
IV
O
Br
2% HBr, 150°C, 8 h
I
II
in the presence of Cu(acac)2. In the reaction catalyzed
by Cu(acac)2–HBr the major product was dicyclohexyl
ether (II). When only HBr was used as catalyst, the
conversion of I decreased to 18%, and the yield of
cyclohexyl bromide (III) appreciably increased
(Scheme 4). Raising the concentration of hydrogen
bromide (aqueous solution) to 8–20% resulted in the
formation of cyclohexyl bromide (III) as the major
product (Table 2).
C10H17O4Br3Cu. Calculated, %: C 23.79; H 3.37; O
13.00; Br 47.52 (Table 3). We also tried to determine
the composition of the catalyst isolated after the reac-
tion was performed under standard conditions [150°C,
8 h, Cu(acac)2–CBr4–I 1:5:100]. Its elemental com-
position turned out to approach that of Cu(acac)2·
2.5HBr: Found, %: C 22.53; H 2.51; O 9.89; Br 43.61.
C10H16.5O4Br2.5Cu. Calculated, %: C 25.08; H 3.06;
O 13.08; Br 43.00. When gaseous hydrogen bromide
was passed through a mixture containing cyclohexanol
and Cu(acac)2, the major product was cyclohexyl
bromide (III) despite high conversion of cyclohexanol
(75%). These findings led us to presume that the true
catalyst in the system Cu(acac)2–CBr4–alcohol is the
complex Cu(acac)2·2.5HBr which is generated in situ;
this complex is more active than Cu(acac)2·3HBr pre-
pared preliminarily from Cu(acac)2 and HBr.
Participation of Cu(acac)2 ·HBr in the catalytic
series was verified by experiments with that complex
synthesized preliminarily. Heating of cyclohexanol (I)
in the presence of Cu(acac)2 ·HBr prepared by treat-
ment of crystalline Cu(acac)2 with gaseous HBr afford-
ed 18% of II. The composition of the preliminarily
synthesized Cu(acac)2–HBr complex was estimated at
1:3. Found, %: C 17.66; H 2.82; O 10.20; Br 45.71.
Table 2. Effect of HBr concentration (aqueous solution) on the yield of dicyclohexyl ether (II)a
Yield, %
Concentration
of HBr, %
Conversion of
cyclohexanol (I), %
Catalyst
II
III
05
04
52
40
69
73
IV
0
–
02
02
08
08
20
20
18
33
68
66
77
83
13
25
16
22
08
09
Cu(acac)2
4
–
0
Cu(acac)2
–
4
0
Cu(acac)2
1
a
Temperature 150°C, reaction time 8 h.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

KHUSNUTDINOV et al.
1194
Table 3. Effect of Cu(acac)2·nHBr complexes on the yield of dicyclohexyl ether (II)a
Yield, %
Conversion of
cyclohexanol (I), %
Catalytic system
Catalyst compositionb
II
III
IV
Cu(acac)2·nHBrc + cyclohexanol
Cu(acac)2·3HBrc
Cu(acac)2·2.5HBrd
022
100
18
95
2
3
2
2
Cu(acac)2–CBr4 + cyclohexanol
a
b
c
d
150°C, 8 h.
According to elemental analysis data.
Preliminarily prepared complex.
Complex generated in situ and isolated after reaction completion.
Another cyclic alcohol, cyclopentanol (VI) at
150°C in 8 h was converted into dicyclopentyl ether
(VII) in 95% yield (Scheme 5).
dration followed by addition of alcohol to the resulting
olefin to the formation of ether. For this purpose,
cyclohexanol (I) was brought into reaction with cyclo-
pentene in the presence of Cu(acac)2–CBr4 [150°C,
4 h, Cu(acac)2–CBr4–cyclohexanol–cyclopentene
1:5:50: 50]. The reaction gave a mixture of 7% of
dicyclohexyl ether (II), 8%, of cyclohexyl cyclopentyl
ether (IX), 8% of cyclohexyl bromide (III), and 15%
of cyclohexene (X) (Scheme 7).
Scheme 5.
Cu(acac)2–CBr4
150°C, 8 h
OH
O
VI
VII
Primary aliphatic alcohols underwent catalytic
dehydration in the presence of Cu(acac)2–CBr4 under
more severe conditions (175–200°C, 8–16 h;
Scheme 6). The conversion of the alcohol and the yield
of the corresponding ether strongly depended on the
length of the hydrocarbon chain: the yield decreased
from 92 to 33% as the length of the alkyl radical
increased in going from butan-1-ol to undecan-1-ol.
Favorable conditions for the synthesis of ethers from
primary alcohols were temperature 200°C and reaction
time 10 h. Reduction of the temperature to 175°C
required twice as long reaction time to attain a high
yield of ether. Such long-chain alcohols as tridecan-1-
ol and hexadecan-1-ol were not converted into ethers
under the above conditions (200°C, 10 h), whereas
raising the temperature to 250°C resulted in their
intramolecular dehydration to give the corresponding
alkenes.
Scheme 7.
OH
+
I
1 : 1
Cu(acac)2–CBr4
150°C, 4 h
O
Br
+
Conversion of I 38%
II
III
O
+
+
IX
X
The product structure (specifically, the formation of
ethers II and IX) indicated that both reaction paths are
operative. Cyclohexene is formed during the process
via dehydration of cyclohexanol. Despite the presence
of unreacted cyclohexanol in the reaction mixture, the
addition of I to cyclopentene was not complete.
Additional information on the reaction mechanism
was obtained by studying the reaction of cyclohexanol
(I) with methanol-d4 (CD3OD) [150°C, 10 h,
Cu(acac)2–CBr4–cyclohexanol–CD3OD 1:5:100:100;
Scheme 8]. According to the GC–MS data, the reaction
mixture contained cyclohexyl methyl ether molecules
with different concentrations of deuterium, D3-XI
(m/z 117 [M]+, yield 29%) and D4-XII (m/z 118 [M]+,
yield 3% on the reacted cyclohexanol). The conversion
of cyclohexanol was not complete (82%). In addition,
45% of cyclohexene was detected in the reaction mix-
Scheme 6.
Cu(acac)2–CBr4
200°C, 10 h
ROH
ROR
VIIIa–VIIIf
R = C4H9 (a), C5H11 (b), C6H13 (c), C7H15 (d),
C8H17 (e), C11H23 (f).
Insofar as the reaction under study occurs at ele-
vated temperature (150–200°C) which favors dehydra-
tion of alcohols to olefins, our further experiments
were aimed at estimating the relative contributions of
intermolecular dehydration and intramolecular dehy-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

INTERMOLECULAR DEHYDRATION OF ALCOHOLS
1195
Scheme 8.
Cu(acac)2–CBr4
150°C, 10 h
OH
OCD3
OCD3
D
O
+
CD3OD
+
+
+
Conversion of I 38%
I
1 : 1
XI
XII
II
X
10 : 1 : 2 : 15
ture. Scheme 9 illustrates the mechanism of formation
of isotopic congeners XI and XII. Neither CD3OH nor
C6H11OD H–D exchange product was detected by GC–
MS in a 1:1 mixture of cyclohexanol with methanol-d4
kept over a period 4 days at room temperature or at
60°C. These findings indicated that ethers XI and XII,
as well as II and IX, are formed according to both
reaction paths, but the contribution of the second path
is smaller.
Commercially available methanol, ethanol, propan-
1-ol, propan-2-ol, butan-1-ol, pentan-1-ol, cyclopen-
tanol, hexan-1-ol, cyclohexanol, heptan-1-ol, octan-1-
ol, phenylmethanol, undecan-1-ol, tridecan-1-ol, hexa-
decan-1-ol, cyclopentene, carbon tetrachloride, bromo-
form, chloroform, and carbon tetrabromide were dis-
tilled or recrystallized prior to use. Copper(I) chloride,
copper(I) bromide, copper(I) iodide, copper(II) bro-
mide, copper(II) acetylacetonate Cu(acac)2, copper(II)
acetate Cu(OAc)2, copper(II) salicylate Cu(C7H8O6)2,
copper(II) chloride dihydrate CuCl2 ·2H2O, and cop-
per(II) benzoate dihydrate Cu(C7H5O2)2·2H2O (Acros
Organics) were preliminarily dried in a vacuum desic-
cator. Gaseous hydrogen bromide was prepared ac-
cording to the procedure described in [11]. Hydro-
bromic acid (39.3%) was distilled prior to use.
Scheme 9.
OCD3
CD3OD
–HDO
OH
XI, 29%
OCD3
CD3OD
I
–H2O
All reactions were carried out in a 10-ml glass am-
pule placed into a 17-ml stainless steel high-pressure
microreactor under controlled heating and steering.
D
XII, 3%
X
We can conclude that catalytic systems based on
copper compounds are more advantageous than min-
eral acids due to their universal character and high
selectivity for ethers which is achieved as a result of
almost complete suppression of intramolecular dehy-
dration of alcohols with formation of olefins.
General procedure for the synthesis of ethers
from alcohols II–VIIIa. An ampule was charged
under argon with 0.0052 g (1 mmol) of Cu(acac)2,
0.03 g (5 mmol) of CBr4, and 0.2 ml (100 mmol) of the
corresponding alcohol. The ampule was sealed and
placed into a high-pressure reactor which was hermeti-
cally closed and heated at 150–250°C for 4–20 h under
continuous stirring. When the reaction was complete,
the reactor was cooled to 20°C, the ampule was
opened, the mixture was neutralized with 10% aqueous
sodium carbonate under stirring for 0.5–1 h on
a magnetic stirrer, the organic phase was separated, the
aqueous phase was extracted with chloroform, and the
extract was passed through a layer of silica gel (2 g)
using hexane as eluent. The solvent was distilled off,
and the residue was distilled under reduced pressure or
recrystallized from benzene–hexane.
EXPERIMENTAL
1
The H and 13C NMR spectra were measured on
a Bruker Avance-400 spectrometer at 400.13 and
100.62 MHz, respectively, from solutions in CDCl3
using tetramethylsilane as reference. The mass spectra
were run on a Shimadzu GCMS-QP2010Plus instru-
ment (SPB-5 capillary column, 30 m×0.25 mm; carrier
gas helium; oven temperature programming from 40 to
300°C at a rate of 8 deg/min; injector temperature
280°C, ion source temperature 200°C; electron impact,
70 eV). GLC analyses were run on Shimadzu GC-9A
and GC-2014 instruments (2 m×3-mm column packed
with 5% of SE-30 on Chromaton N-AW-HMDS; oven
temperature programming from 50 to 270°C at a rate
of 8 deg/min; carrier gas helium, flow rate 47 ml/min).
The elemental compositions were determined on
a Carlo Erba 1106 analyzer.
The structure of the isolated compounds was
proved by spectral data and by comparing with authen-
tic samples and reference data: dicyclohexyl ether (II,
yield 95%), dicyclopentyl ether (VII, 95%) [9, 11],
dibutyl ether (VIIIa, 92%), dipentyl ether (VIIIb,
90%) [12], dihexyl ether (VIIIc, 84%), diheptyl ether
(VIIId, 82%), dioctyl ether (VIIIe, 80%) [2].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

KHUSNUTDINOV et al.
1196
2. Olah, G.A., Shamma, T., and Prakash, G.K.S., Catal.
Lett., 1997, vol. 46, p. 1.
3. Olah, G.A., US Patent no. 5520710, 1996; Chem.
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5. Habenicht, C., Kam, L.C., Wilschut, M.J., and
Antal, M.J., Jr., Ind. Eng. Chem. Res., 1995, vol. 34,
p. 3784.
Cyclohexyl cyclopentyl ether (IX). Yield 8%,
bp 100–101°C (9 mm). H NMR spectrum, δ, ppm:
1
1.05–2.05 m (18H, CH2), 3.20–3.35 m (1H, CH in
cyclohexyl), 3.80–4.10 m (1H, CH in cyclopentyl).
13C NMR spectrum, δC, ppm: 80.27 (C1′), 76.69 (C1),
33.36 (C2, C6), 32.67 (C2′, C5′), 25.84 (C4), 24.58 (C3,
C5), 23.34 (C3′, C4′). Mass spectrum, m/z (Irel, %):
168.27 (14) [M]+, 18 (14), 28 (100), 32 (43), 41 (25),
55 (43), 57 (27), 62 (25), 82 (55), 83 (27), 100 (48).
Found, %: C 78.56; H 12.00; O 9.44. C11H20O. Cal-
culated, %: C 78.51; H 11.98; O 9.51. M 168.27.
6. Dueno, E.E., Chu, F., Kim, S., and Jung, K.W., Tetra-
hedron Lett., 1999, vol. 40, p. 1843.
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J. Mol. Catal., 1984, vol. 26, p. 37.
Diundecyl ether (VIIIf). Yield 33%, bp 135–
137°C (0.2 mm). H NMR spectrum, δ, ppm: 0.88 t
1
(6H, CH3), 1.05–1.75 m (36H, CH2), 3.38 t (4H, CH2).
13C NMR spectrum, δC, ppm: 13.87 (C11, C11′), 22.90
(C10, 10′), 27.55 (C9, C9′), 27.65 (C8, C8′), 27.99 (C7,
C7′), 28.08 (C6, C6′), 28.32 (C5, C5′), 28.92 (C4, C4′),
29.23 (C3, C3′), 31.53 (C2, C2′), 70.83 (C1, C1′). Mass
spectrum: m/z 326.60 [M]+. Found, %: C 80.95;
H 14.10; O 4.95. C22H46O. Calculated, %: C 80.90;
H 14.20; O 4.90. M 326.60.
8. Kim, S., Chung, K.N., and Yang, S., J. Org. Chem.,
1987, vol. 52, p. 3917.
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ganicheskoi khimii (Laboratory Works on Inorganic
Chemistry), Spitsin, V., Ed., Moscow: Mosk. Gos.
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