Pinacol Coupling Reaction of Aromatic Aldehydes Mediated by Zn in Acid Aqueous Media under Ultrasound Irradiation

Article abstract of DOI:10.1081/SCC-120028629

Pinacol coupling of aromatic aldehydes by Zn powder in aqueous H ₂NSO₃H or H₃PO₄ under ultrasound irradiation can lead to the corresponding pinacols in 14-88% yields.

Full text of DOI:10.1081/SCC-120028629

w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 6, pp. 993–1000, 2004
Pinacol Coupling Reaction of Aromatic
Aldehydes Mediated by Zn in Acid
Aqueous Media Under Ultrasound
Irradiation
*
Jin-Hui Yang, Ji-Tai Li, Jun-Ling Zhao, and Tong-Shuang Li
College of Chemistry and Environmental Science, Hebei University,
Hebei Province, Baoding, P.R. China
ABSTRACT
Pinacol coupling of aromatic aldehydes by Zn powder in aqueous
2 3 3 4
H NSO H or H PO under ultrasound irradiation can lead to the corres-
ponding pinacols in 14–88% yields.
Key Words: Pinacol coupling; Acid aqueous media; Ultrasound
irradiation.
[1]
1,2-Diols are very useful synthons for a variety of organic syntheses,
and which have been used as intermediates for the construction of biologically
*
Correspondence: Ji-Tai Li, College of Chemistry and Environmental Science, Hebei
University, Hezuo Road No. 88, Hebei Province, Baoding 071002, P.R. China;
Fax: þ86-312-5079628; E-mail: orgsyn@mail.hbu.edu.cn.
9
93
DOI: 10.1081/SCC-120028629
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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9
94
Yang et al.
[2]
important natural product skeletons. The formation of 1,2-diol has been
[
3]
[4]
attempted using a number of reagents such as Mg, Mn, Al, In,
[5]
[6]
[
7,8]
[9]
and rare earth metal. However, some of the reductants
transition metal
used are expensive or the reduction conditions are critical and these reactions
are often associated with the toxic reagents and heavy metals, which would
lead to economic and environmental concerns.
Organic reactions in water or aqueous media have attracted increasing
interest currently because of the environmental issue and understanding
biochemical processes. Water offers many practical and economic advantages
as a reaction solvent, including low cost, safe handling and environmental
compatibility. Recently, pinacol coupling reaction in aqueous media has been
[
3,5]
described in the literature;
however, these methods so far suffer from harsh
reaction and workup conditions, using an excess amount of metal or have a
long reaction time.
Ultrasound has increasingly been used in organic synthesis in the last three
decades. Compared with traditional methods, this technique is more conveni-
ent and easily controlled. A large number of organic reactions can be carried
out in higher yields, shorter reaction time and milder conditions under ultra-
[
10]
[6]
sound irradiation.
with indium in neutral aqueous media using sonication affording the corre-
Lim et al. reported the reaction of aromatic aldehydes
[7]
sponding diols in moderate to good yield; Basu et al. reported the reduction
of several aromatic ketones to diols by samarium in the presence of ammonium
chloride under sonication at room temperature, and the reaction could be
[11]
completed within 5 min; Mecarova and Toma reported the pinacol coupling
reaction in aqueous media under ultrasound irradiation and found that ultra-
sound considerably accelerates the benzaldehydes conversion. Our laboratory
has also reported the pinacol coupling of aromatic aldehydes and ketones in
[12–15]
aqueous media under ultrasound irradiation.
Herein, we wish to report
the results of the pinacol coupling reaction of aromatic aldehydes by Zn in
aqueous H NSO H (1N) or H PO (3N) under ultrasound irradiation (Sch. 1).
When the substrate is 3-ClC H CHO, we did the experiment using
2
3
3
4
6
4
reaction system A: Zn (0.195 g, 3 mmol)/H NSO H (1N) and system B: Zn
2
3
2 3
Scheme 1. A: Zn (0.195 g, 3 mmol)/H NSO H (1N); B: Zn (0.195 g, 3 mmol)/
H PO (3N).
3
4

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Pinacol Coupling Reaction of Aromatic Aldehydes
995
Table 1. Optimization of pinacol coupling of 3-ClC
under ultrasound irradiation.
6
H
4
CHO in acidic aqueous media
Reaction
a
system
Ultrasound irradiation
frequency (kHz)
Reaction
time (h)
Isolated
yield (%)
Entry
1
A
B
A
B
A
B
B
25
25
40
40
59
59
25
25
25
2.5
2.5
2.5
2.5
2.5
2.5
2.0
2.5
2.5
74
88
72
79
71
64
73
67
81
2
3
4
5
6
b
B
c
B
a
A: Zn (0.195 g, 3 mmol)/H
The amount of Zn is 0.13 g.
2
NSO
3
H (1N); B: Zn (0.195 g, 3 mmol)/H
3
PO
4
(3N).
b
c
3 4
The concentrate of H PO is 2N.
(0.195 g, 3 mmol)/H PO (3N). From the result in Table 1, we found that
3 4
ultrasound irradiation frequency has little effect on the reaction yield (74%,
7
7
2% and 71%, respectively) for system A, but for B, the yield of pinacol (88%,
9% and 64%, respectively) significantly decreases following the enhance-
ment of ultrasound irradiation frequency. From Table 1, we also found that for
system B, prolonging the reaction time from 2.0 to 2.5 hr, the yield of pinacol
increases from 73% (entry 4) to 88% (entry 1) under 25 kHz ultrasound
irradiation. When lowering the amount of Zn (0.13 g) or the concentration of
H PO (2N) is lowered, the yield of pinacol decreased to 67% (entry 5) and
3
4
81% (entry 6) respectively, compared with that 88% (entry 1).
An alternative and often competing reaction to pinacolization is reduction
to the corresponding alcohol. In the present process, pinacol reaction was
found mainly. Coupling is propagated by single-electron reduction of the
carbonyl group to form a ketyl radical anion (I), which either undergoes
radical–radical coupling (route a), or is further reduced to the corresponding
dianion (II) and then nucleophilically attacks a second carbonyl group (route
þ
b), so leading to pinacol formation, while dianion (2) can be protonated by H
[2,7]
to generate minority of alcohol (Sch. 2).
From the result in Table 1, the reaction conditions we choose are A: Zn
(
(
0.195 g, 3 mmol)/H NSO H (1N, 5 mL) and B: Zn (0.195 g, 3 mmol)/H PO
4
3N, 5 mL). Using these two reaction systems, we did a series of experiments
2
3
3
for pinacol coupling of aromatic aldehydes under ultrasound irradiation.
As shown in Table 2, some aromatic aldehydes via pinacol coupling can
give pinacols in good yields in acidic aqueous media under ultrasound

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9
96
Yang et al.
Scheme 2.
irradiation. For system A, when the substrates are 1a, 1b and 1h, the
corresponding pinacol product was obtained in 74%, 70% and 63% yield
respectively for 2.5 hr ultrasound irradiation; for system B, the yield of pinacol
was 88%, 85% and 79% respectively, which also indicated that higher yield of
Table 2. Pinacol coupling of aromatic aldehydes in acidic aqueous media under
ultrasound irradiation.
Reaction
a
system
Isolated
yield (%)
b
c
R
f
Entry
Substrates
dl/meso
a
3-ClC
2-ClC
6
6
H
4
4
CHO
CHO
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
74
88
70
85
21
45
42
34
54
43
23
49
14
28
63
79
38/62
46/54
18/82
24/76
—
0.444
0.456
0.284
0.221
0.448
0.294
0.222
0.500
b
c
d
e
f
H
PhCHO
4-ClC CHO
2,4-Cl CHO
—
6
H
4
—
—
2
C
6
H
3
—
—
—
4-CH C H CHO
3 6 4
—
—
g
h
3,4-(OCH
2
O)C
6
H
3
CHO
—
33/67
31/69
3-BrC H CHO
6
4
a
2 3 3 4
A: Zn (0.195 g, 3 mmol)/H NSO H (1N); B: Zn (0.195 g, 3 mmol)/H PO (3N).
Ratio of dl/meso was calculated by HNMR.
b
1
c
Eluant: petroleum ether/diethyl ether (V : V) ¼ 1 : 1.

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Pinacol Coupling Reaction of Aromatic Aldehydes
997
pinacols can be obtained under system B compared to system A. In contrast,
electron-withdrawing groups in the aromatic ring of liquid aromatic aldehydes
(
entry a, b, h) increase the reactivity. Electron-withdrawing groups in the
aromatic ring of solid aromatic aldehydes (entry d, e) and the aromatic
aldehydes with electron donating group (entry f) show less reactivity. The
steric hinderance around the carbonyl group (entry e, g) inhibits the coupling
reaction.
The pinacol coupling reaction can form dl and meso stereoisomers; we
easily found that in system A and system B, higher meso-stereoisomer was
obtained except that the rate of dl/meso was nearly 1 : 1 (entry a).
In summary, ultrasound irradiation can efficiently prompt pinacol
coupling of some aromatic aldehydes in acidic aqueous media. The main
advantage of the present procedure is the milder reaction conditions, in-
expensive reagent and operational simplicity.
EXPERIMENTAL
Liquid aldehydes were distilled before use. IR spectra were recorded on
Bio-Rad FTS-40 spectrometer (KBr). MS were determined on a VG-7070E
1
spectrometer (El, 70 eV). H NMR spectra was measured on Bruker AVANCE
400 (400 MHz) spectrometer using TMS as internal standard and CDCl as
3
solvent. Sonication was performed in Shanghai Branson-CQX ultrasonic
cleaner (with a frequency of 25 kHz and a nominal power 250 W) and SK 250
LH ultrasonic cleaner (with a frequency of 40 kHz, 59 kHz and a nominal
power 250 W; Shanghai Kudos Ultrasonic Instrument Co., Ltd.). The reaction
flasks were located in the maximum energy area in the cleaner, where the
surface of reactants is slightly lower than the level of the water. The reaction
temperature was controlled by addition or removal of water from the
ultrasonic bath.
General Procedure for the Pinacol Coupling of Aromatic
Aldehydes in Acidic Media Under Ultrasound Irradiation
A 10 mL Pyrex flask was charged with the desired aldehyde (1 mmol), Zn
powder (0.195 g, 3 mmol) and Zn/H NSO H (1N, 5 mL) or Zn/H PO (3N,
2
3
3
4
5
mL). The mixture was irradiated in the water bath of an ultrasonic cleaner
under an air conditions at 25–308C for 2.5 hr. After the completion of the
reaction, the resulting suspension was filtered to remove the Zn powder. The
filtrate was extracted with ethyl acetate (3 Â 15 mL). The combined organic

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9
98
Yang et al.
layers were washed with saturated aqueous NaHCO solution and brine, dried
3
over anhydrous magnesium sulfate for 12 hr and filtered. Ethyl acetate was
evaporated under reduced pressure to give the crude product, which was
separated by column chromatography on silica (200–300 mesh), eluted with
petroleum ether or a mixture of petroleum ether and diethyl ether. All the
products were confirmed by comparing their R value with that of the authentic
f
1
samples, and IR, MS, H NMR, spectral data.
1
a. H NMR: d 3.29 (4H, b, OH), 4.56 (2H, s, CH, dl), 4.74 (2H, s, CH,
2
meso), 6.87–7.36 (16H, m, Ph-H). m/z (%): 263 (1.2), 251 (1.6), 178 (4.6),
65 (4.6), 141 (100), 113 (23.8), 77 (71.0). IR (KBr) v: 3260–3318.
1
1
b. H NMR: d 2.66 (2H, s, OH, meso), 2.76 (2H, s, OH, dl), 5.39 (2H, s,
2
CH, dl), 5.63 (2H, s, CH, meso), 7.17–7.70 (16H, m, Ph-H). m/z (%): 282 (1),
165 (47), 141 (89), 113 (13), 107 (14), 77 (100), 51 (38). IR (KBr) v: 3100–
3
500.
1
c. H NMR: d 2.20 (2H, s, OH, meso), 2.83 (2H, s, OH, dl), 4.72 (2H, s,
2
CH, dl), 4.84 (2H, s, CH, meso), 7.14–7.32 (20H, m, Ph-H). m/z (%): 214 (1),
1
3
80 (7.6), 167 (12.5), 149 (6.0), 107 (93.8), 79 (100), 77 (73.8). IR (KBr) v:
200–3480.
1
d. H NMR: d 1.47 (6H, s, CH , dl), 1.54 (6H, s, CH , meso), 2.28 (2H, s,
2
3
3
OH, meso), 2.57 (2H, s, OH, dl), 7.08–7.30 (16H, m, Ph-H). m/z (%): 276
14), 249 (32), 155 (100), 111 (8). IR (KBr) v: 3380–3420.
(
1
e. H NMR: d 3.46 (4H, s, OH), 5.15 (2H, s, CH, dl), 5.47 (2H, s, CH,
2
meso), 7.10–7.26 (12H, m, Ph-H). m/z (%): 352 (1), 305 (1.4), 233 (10), 175
(
100), 145 (10), 111 (25), 77 (15). IR (KBr) v: 3320–3400.
2
1
f. H NMR: d 2.06 (2H, s, OH, meso), 2.75 (2H, s, OH, dl), 4.68
(
2H, s, CH, dl), 4.75 (2H, s, CH, meso) 7.04–7.26 (16H, m, Ph-H). m/z
%): 242 (1.2), 195 (6), 121 (100), 107 (12), 77 (13). IR (KBr) v: 3280–
(
3450.
2
1
g. H NMR (DMSO as solvent): d 4.44 (4H, s, OH), 5.14 (2H, s, CH, dl),
5
.27 (2H, s, CH, meso), 5.96 (8H, s, CH ), 6.52–6.82 (12H, m, Ph-H). m/z
2
(
%): 302 (1), 284 (2.5), 268 (5.0), 255 (11.8), 151 (100), 123 (32), 93 (77.1),
5 (39.0). IR (KBr) v: 3100–3600.
6
1
h. H NMR: d 2.36 (2H, s, OH, meso), 2.93 (2H, s, OH, dl), 4.65 (2H, s,
2
CH, dl), 4.81 (2H, s, CH, meso), 6.97–7.46 (16H, m, Ph-H). m/z (%): 325 (6),
186 (16), 157 (8), 107 (7), 77 (100), 51 (13). IR (KBr) v: 3200–3500.
ACKNOWLEDGMENTS
This project was supported by Educational Ministry of China, Educa-
tional Department of Hebei Province (2001104) and Natural Science
Foundation of Hebei Province, China (203107).

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Received in Japan July 25, 2003

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