Zirconium tetrachloride catalysed synthesis of symmetric and unsymmetric ethers from secondary benzylic alcohols

Article abstract of DOI:10.3184/030823407X270392

Secondary benzylic alcohols are coupled in the presence of zirconium tetrachloride to afford the corresponding symmetrical ethers in good yields. Unsymmetric ethers are obtained with good selectivity by condensation of two different secondary benzylic alcohols under the action of the same catalyst.

Full text of DOI:10.3184/030823407X270392

JOURNAL OF CHEMICAL RESEARCH 2007
DECEMBER, 717–719
RESEARCH PAPER 717
Zirconium tetrachloride catalysed synthesis of symmetric and
unsymmetric ethers from secondary benzylic alcohols†
Biswanath Das*, Maddeboina Krishnaiah, Boyapati Veeranjaneyulu, Yallamalla Srinivas and
Yerra Koteswara Rao
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Secondary benzylic alcohols are coupled in the presence of zirconium tetrachloride to afford the corresponding
symmetrical ethers in good yields. Unsymmetric ethers are obtained with good selectivity by condensation of two
different secondary benzylic alcohols under the action of the same catalyst.
Keywords: symmetric ethers, unsymmetric ethers, ZrCl4, secondary benzylic alcohol
Etherification by direct coupling of alcohols is a useful
method in organic synthesis.1 The reaction is generally carried
out by using a small amount of an inorganic or organic acid.
The Williamson ether synthesis,2 one of the most commonly
used methods, requires the conversion of alcohols to halides
or tosylates. Various Lewis acids such as FeCl3,3 BiBr3,4
ZnCl2,6 GaCl3,6 methylrhenium trioxide7 and rare earth metal
triflates8 can also catalyse the etherification. However, many
of these methods suffer from drawbacks such as the use of
expensive reagent or stiochiometric amount of catalyst, harsh
reaction conditions, longer reaction times, high temperature
and low yields.
Recently, ZrCl4 has been used in various chemical
transformations as it possesses an interesting reactivity,
is less costly and is less toxic than some alternatives.10
The reagent has been employed in the synthesis of nitriles,11
oxidation of alcohols,12 selective tosylation of alcohols,13
tetrahydropyranylation and detetrahydropyranylation of
alcohols and phenols.14 Here we describe the catalytic activity
of ZrCl4 in the etherification of secondary benzylic alcohols.
We have developed a mild and efficient method for direct
preparation of symmetrical and unsymmetrical ethers using
catalytic amount of zirconium tetrachloride. The major
advantages of this protocol include short reaction times,
availability of the catalyst, high yields, good selectivity and
simple experimental procedure.
In continuation of our synthetic work,9 we have discovered
a suitable method for the direct preparation of symmetric
and unsymmetric ethers by using a catalytic amount of ZrCl4
under reflux. Various secondary benzylic alcohols having
electron-donating groups underwent the reaction smoothly
to furnish the ethers in good yields (Scheme 1) while the
substrates having electron withdrawing groups afforded the
products with lower yields.
Experimental
The spectra were determined with the following instruments: Melting
points were measured on a Büchi 510 instrument and are uncorrected.
IR, Perkin Elmer spectrophotometer; NMR, Varian Gemini 200 MHz
and MS: Micromass VG 7070 H (70 eV), Column chromatography
was performed over silica gel (BDH, 100–200 mesh) and TLC with
The reaction was complete within 1–3 h (Table 1).
Unsymmetrical ethers were also formed with good selectivity
by coupling of two different benzylic alcohols in the presence
of the catalyst (Table 2). However, in the case of cyclic
benzylic alcohols, olefins are produced in high yields at room
temperature (Scheme 2, Table 3). The structures of the products
were determined from their spectral (1H NMR and MS) data.
silica gel GF254
.
General procedure for the synthesis of symmetric and unsummetric
ethers
To a mixture of a secondary benzylic alcohol (1 mmol) (or two
different secondary benzylic alcohols [0.5 mmol each]) in acetonitrile
(5 ml), ZrCl4 (0.2 mmol) was added. The mixture was stirred at
reflux and the reaction was monitored by TLC. After completion,
OH
ZrCl4
O
CH3CN
reflux, 1-3 h.
MeO
MeO
OMe
NO2
85%
Ph
OH
OH
Ph
ZrCl4
O
+
CH3CN
reflux, 1-3 h.
O2N
72%
Scheme 1
OH
ZrCl4
MeO
MeO
CH3CN
r. t., 45 min.
90-92%
Scheme 2
* Correspondent. E-mail: biswanathdas@yahoo.com
† Part 155 in the series, “Studies on novel synthetic methodologies”.
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718 JOURNAL OF CHEMICAL RESEARCH 2007
a
Table 1 Formation of symmetric ethers from sec-benzylic alcohols catalysed by ZrCl4
Entry
Substrate
Product
Time/h
Isolated
yield/%
M. p./°C
(reported)lit
OH
O
O
1
2
1
85
80
Liquid
Liquid
MeO
OMe
MeO
OH
OH
1.5
O
3
1.5
85
Liquid
Cl
Cl
Cl
OH
O
O
4
5
2
3
86
55
Liquid (liquid)6
146–148
OH
OH
O2N
O2N
NO2
O
6
7
2
1
78
95
92–94
HO
HO
OH
OH
Ph
Ph
Ph
90–92 (89–91)6
O
aAll the products were characterised from spectral (1H NMR and MS) data.
Table 2 Formation of unsymmetric ethers by coupling of different alcohols catalysed by ZrCl4
a
Entry
Alcohol A
Alcohol B
Product
Time/h
Isolated
yield/%b
M. p./°C
(reported)lit
Ph
O
OH
Ph
OH
8
9
1.5
74b
72b
Liquid
Cl
Cl
Ph
O
OH
OH
Ph
2
117–119
NO2
O2N
OH
Ph
O
OH
OH
OH
Ph
Ph
Ph
10
11
2.5
2
70b
75b
Liquid
Liquid
OH
Ph
O
MeO
OMe
Ph
O
OH
12
13
3
3
76
64
Liquid
OH
O
OH
Liquid (liquid)6
aAll the products were characterised from spectral (1H NMR and MS) data.
bSymmetric bis (diphenyl)methyl ether was formed in small quantity (7–10%) as determined by 1H NMR spectrum of the crude product.
the mixture was diluted with EtOAc (10 ml) and washed with brine
(20 ml) and water (2 ¥ 10 ml). The organic layer was separated, dried
over Na2SO4 and concentrated under vacuum. The crude product was
purified by column chromatography (silica gel, hexane: EtOAc) to
afford the pure ether.
1H NMR (CDCl3, 200 MHz): 7.27–7.10 (m, 2H), 6.82–6.65 (m, 6H),
4.46 (q, J = 6.7 Hz, 1H), 4.18 (q, J = 6.7 Hz, 1H), 3.82 (s, 3H), 3.71
(s, 3H), 1.44 (d, J = 6.7 Hz, 3H), 1.34 (d, J = 6.7 Hz, 3H); FABMS:
m/z 309 [M + Na]+; Anal. Calc. for C18H22O3: C, 75.5; H, 7.7%.
Found: C, 75.5; H, 7.5%.
The spectral data of some of the representative ethers (Table 1–3)
are given below.
(2): Colourless liquid IR (KBr): 3021, 1486, 1350, 1086 cm-1;
1H NMR (CDCl3, 200 MHz): 7.15–699 (m, 8H), 4.41 (q, J = 6.5 Hz,
1H), 4.13 (q, J = 6.5 Hz, 1H), 2.23 (s, 3H), 2.16 (s, 3H), 1.35 (d,
(1): Colourless liquid IR (KBr): 2926, 1602, 1258, 1046 cm-1;
PAPER: 07/4958

JOURNAL OF CHEMICAL RESEARCH 2007 719
a
Table 3 Formation of alkenes from cyclic benzylic alcohols catalysed by ZrCl4
Entry
Substrate
Product
Time/min
Isolated
yield/%b
M. p. (°C)
(reported)lit
OH
14
45
92(5)
90(6)
Liquid
MeO
MeO
MeO
MeO
OH
15
45
Liquid (liquid)8
OH
MeO
MeO
16
17
70
40
73(10)
89
Liquid (liquid)8
80–82 (79–81)8
OH
aAll the products were characterised from spectral (1H NMR and MS) data.
bYield reported in parentheses is for corresponding symmetrical ether.
J = 6.4 Hz, 3H), 1.32 (d, J = 6.4 Hz, 3H); FABMS: m/z 277 [M +
Na]+; Anal. Calc. for C18H22O: C, 85.0; H, 8.7%. Found: C, 85.1;
H, 8.6%.
(12): Colourless liquid; IR (KBr); 2974, 2866, 1453, 1493, 1096
cm-1; 1H NMR (CDCl3, 200 MHz): 7.35–7.14 (m, 10H), 5.38 (s, 1H),
3.45 (q, J = 7.2 Hz, 2H), 1,25 (t, J = 7.2 Hz, 3H); FABMS: m/z 235
[M + Na]+; Anal. Calc. for C15H15O: C, 85.30; H, 7.10%. Found: C,
85.22; H, 7.24%.
Compound (3): Colourless liquid IR (KBr): 3061, 1496, 1450,
1090 cm-1; 1H NMR (CDCl3, 200 MHz): 7.35–7.12 (m, 8H), 4.40 (q,
J = 6.5 Hz, 1H), 4.12 (q, J = 6.5 Hz, 1H), 1.40 (d, J = 6.8 Hz, 3H),
1.32 (d, J = 6.8 Hz, 3H); FABMS: m/z 317, 319, 321 [M + Na]+; Anal.
Calc. for C16H16Cl2O: C, 64.9; H, 5.4%. Found: C, 64.8; H, 5.3%.
(5): White solid; m. p. 146-148°C; IR (KBr): 2925, 2854, 1522,
(14): Colourless liquid; IR (KBr); 3032, 2996, 1480, 1453, 1245,
1
cm-1; H NMR (CDCl3, 200 MHz): 6.90 (d, J = 8.0, 1H), 6.66–6.57
(m, 2H), 6.35 (d, J = 9.0, 1H), 5.85 (m, 1H), 3.75 (s, 3H), 2.76
(t, J = 7.0, 2H), 2.31–2.20 (m, 2H); FABMS: m/z 183 [M + Na]+;
Anal. Calc. for C11H12O: C, 82.50; H, 7.50%. Found: C, 82.46; H,
7.61%.
1
1347, 1236, 1066 cm-1; H NMR (CDCl3, 200 MHz): 8.21 (m, 4H),
7.55 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 5.86 (q, J = 6.5 Hz,
1H), 4.25 (q, J = 6.5 Hz, 1H), 1.58 (d, J = 6.4 Hz, 3H), 1.42 (d,
J = 6.4 Hz, 3H); FABMS: m/z 339 [M + Na]+; Anal. Calc. for
C16H16N2O5: C, 60.7; H, 5.1; N, 8.86%. Found: C, 60.8; H, 5.1; N,
8.8%.
(6): White solid; m.p. 92–94 °C; IR (KBr); 3246, 1630, 1520, 1086
cm-1; 1H NMR (CDCl3, 200 MHz): 7.21–7.12 (m, 2H), 6.65–6.75
(m, 6H), 4.46 (q, J = 6.5 Hz, 1H), 4.12 (q, J = 6.5 Hz, 1H), 1.43 (d,
J = 6.5 Hz, 3H) 1.32 (d, J = 6.5 Hz, 3H); FABMS: m/z 281
[M + Na]+; Anal. Calc. for C16H18O3: C, 74.4; H, 7.0%. Found: C,
74.3; H, 6.8%.
The authors thank CSIR, New Delhi for financial assistance.
Received 22 November 2007; accepted 13 December 2007
Paper 07/4958
doi: 10.3184/030823407X270392
References
1
M.B. Smith and J. March, Advanced Organic Chemistry 5th edn, Wiley-
Interscience, New York, 2001, pp. 479-480.
2
D. Barton and W.D. Ollis, Comprehensive Organic Chemistry, Pergamon:
Elmsford, 1979; Vol. 1, p 819.
(8). Colourless liquid; IR (KBr); 3028, 1600, 1492, 1450, 1086 cm-1;
1H NMR (CDCl3, 200 MHz): 7.38–7.12 (m, 14H), 5.15 (s, 1H), 4.39
(q, J = 6.0 Hz, 1H), 1.45 (d, J = 6.0 Hz, 3H); FABMS: m/z 345, 347
[M + Na]+; Anal. Calc. for C21H19ClO: C, 78.0; H, 5.9%. Found: C,
77.7; H, 5.9%.
(9): Light yellow solid; m.p. 117–119°C; IR (KBr); 2923, 2852,
1514, 1343, 1091 cm-1; 1H NMR (CDCl3, 200 MHz): 8.20 (d,
J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.34–7.12 (m, 10H), 5.17
(s, 1H), 4.51 (q, J = 6.3 Hz, 1H), 1.50 (d, J = 6.3, Hz 3H); FABMS:
m/z 356 [M + Na]+; Anal. Calc. for C21H19O3N: C, 75.67; H, 5.70; N,
4.20%. Found: C, 75.54; H, 5.66; N, 4.10%.
3
4
P. Salehi, N. Iranpoor and F.K. Behbahani, Tetrahedron, 1998, 54, 943.
B. Boyer, E.M. Keramane, J.P. Roque and A.A. Pavia, Tetrahedron Lett.,
2000, 41, 2891.
5
6
7
8
S. Kim, K.N. Chung and S. Yang, J. Org. Chem., 1987, 52, 3917.
J. Choi and Y. Kang, Bull. Korean Chem. Soc., 2005, 26, 343.
Z. Zhu and J.H. Espenson, J. Org. Chem., 1996, 61, 324.
(a) A. Kawada, K. Yasuda, H. Abe and T. Harayama, Chem. Pharm. Bull.,
2002, 50, 380; (b) G.V.M. Sharma and A.K. Mahalingam, J. Org. Chem.,
1999, 64, 8943.
9
(a) B. Das, R. Ramu, B. Ravikanth and K.R. Reddy, Tetrahedron Lett.,
2006, 47, 779; (b) B. Das, P. Thirupathi, V.S. Reddy, Y.K. Rao, J. Mol.
Catal. A: Chem. 2006, 247, 233; (c) B. Das, A. Majhi, J. Banerjee,
N. Chowdhury, K.H. Kishore and U.S.N. Murthy, Chem. Pharm.
Bull., 2006, 54, 403; (d) B. Das, M. Krishnaiah and K. Venkateswarlu,
Tetrahedron Lett., 2006, 47, 4457.
(10): Colourless liquid; IR (KBr); 2932, 1532, 1436, 1085 cm-1;
1H NMR (CDCl3, 200 MHz): 7.31–7.06 (m, 14H), 5.16 (s, 1H), 4.30
(q, J = 6.5, Hz 1H), 2.35 (s, 3H), 1.45 (d, J = 6.5 Hz, 3H); FABMS:
m/z 325 [M + Na]+; Anal. Calc. for C22H22O: C, 87.41; H, 7.28%.
Found: C, 87.58; H, 7.36%.
(11): Colourless liquid; IR (KBr); 3028, 1601, 1489, 1258, 1086
cm-1; 1H NMR (CDCl3, 200 MHz): 7.40–7.15 (m, 12H), 6.80 (d,
J = 8.2 Hz, 2H), 5.2 (s, 1H), 4.40 (q, J = 6.4 Hz, 1H), 3.72 (s, 3H),
1.45 (d, J = 6.8 Hz, 3H); FABMS: m/z 341 [M + Na]+; Anal. Calc. for
C22H22O2: C, 83.01; H, 6.91%. Found: C, 83.24; H, 6.98%.
10 J.E. Huheey, Inorganic Chemistry, 3rd edn. Roger and Harper Row,
Singapore, Chap. 18, 1990.
11 C. Tsuji, E. Miyazawa, T. Sakamoto and Y. Kikugawa, Synth. Commun.,
2002, 32, 871.
12 F. Shirini, M.A. Zolfigol and A. Pourhabib J. Chem. Res (S), 2001, 476.
13 B. Das, M.R. Reddy, V.S. Reddy and R. Ramu, Chem Lett., 2004, 33,
1526.
14 N. Rezai, F. Alsadat Meybodi and P. Salehi, Synth. Commun., 2000, 30,
1799.
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