Zn-AlCl3 · 6H2O-mediated reaction in aqueous media: Pinacol coupling reaction

Article abstract of DOI:10.1080/00397911003797833

(Chemical Equation Presented) Vicinal diols have been prepared in good yield by pinacol coupling reaction of aromatic aldehydes and ketones with commercially available zinc and AlCl₃ · 6H₂O in water. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911003797833

This article was downloaded by: [Duke University Medical Center]
On: 03 October 2014, At: 00:10
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Zn-AlCl3 · 6H2O-Mediated Reaction
in Aqueous Media: Pinacol Coupling
Reaction
Binod Kumar Hazarika a & Dilip Kumar Dutta a
a Natural Product Chemistry Division, Northeast Institute of Science
and Technology, Council of Scientific and Industrial Research ,
Jorhat , Assam , India
Published online: 03 Mar 2011.
To cite this article: Binod Kumar Hazarika & Dilip Kumar Dutta (2011) Zn-AlCl3 · 6H2O-Mediated
Reaction in Aqueous Media: Pinacol Coupling Reaction, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:7, 1088-1093, DOI:
10.1080/00397911003797833
To link to this article: http://dx.doi.org/10.1080/00397911003797833
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 41: 1088–1093, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003797833
Zn-AlCl3 Á 6H2O-MEDIATED REACTION IN AQUEOUS
MEDIA: PINACOL COUPLING REACTION
Binod Kumar Hazarika and Dilip Kumar Dutta
Natural Product Chemistry Division, Northeast Institute of Science and
Technology, Council of Scientific and Industrial Research, Jorhat,
Assam, India
GRAPHICAL ABSTRACT
Abstract Vicinal diols have been prepared in good yield by pinacol coupling reaction of
aromatic aldehydes and ketones with commercially available zinc and AlCl3 Á 6H2O in water.
Keywords Aldehydes; aqueous media; diols; ketones; pinacol; Zn-AlCl3 Á 6H2O
INTRODUCTION
Pinacol coupling reaction is an important tool for the synthesis of vicinal diol, which
can be used as an intermediate for the synthesis of several biologically active nat-
urally occurring compounds.[1] Numerous reagents for this reaction such as Al,-Hg[2]
SmI2,[3] SmI2TMSCl,[4] Cr complex,[5] Zn-TMSCl-Ti,[6] Al-KOH,[7] Ce,[8] and
titanium Schiff complexes[9] have been reported. However, some of the metals
require absolutely anhydrous condition under an inert atmosphere, and some
reagents and solvents used are costly, are toxic, or produce undesirable side pro-
ducts. Therefore, the development of simple, cheap, environmentally friendly
reagents and solvents has required great attention in recent years.
Lately, the development of new synthetic methods is based on reducing the
amount of toxic reagents and by-products.[10] In this context, the limited uses of eco-
logically suspected solvents are of considerable importance. In view of the current
thrust to use reactions in aqueous media[11] there is merit in developing this coupling
reaction in water. Moreover, water-mediated reactions are not only important
for economical, environmental, and safety considerations but also show unique
Received January 21, 2010.
Address correspondence to Dilip Kumar Dutta, Natural Products Chemistry Division, Northeast
Institute of Science and Technology, Council of Scientific and Industrial Research, Jorhat 785 006, Assam,
India. E-mail: dkdutta@yahoo.com
1088

PINACOL COUPLING REACTION IN AQUEOUS MEDIA
1089
Scheme 1. Synthesis of vicinal diol.
reactivities and selectivities as compared to organic solvents. Zhang and Li[12] reported
an aqueous reaction to produce diol by magnesium and 0.1 M ammonium chloride in
good yield. Vanadium-catalyzed aqueous reaction[13] is also another effective method
to produce diol. Recently, Wang et al.[14] have reported the coupling of aldehydes and
ketones by metallic aluminium and indium chloride at high temperature. In continu-
ation of our work on metal-assisted reactions,[15] we disclose a new, simple, and green
procedure for the production of vicinal diols using commercially available aluminium
chloride hexahydrate and metallic zinc in water at room temperature.
The results of the reaction (Scheme 1) are summarised in Table 1. A wide range
of aldehydes and ketones were taken as substrates for this study. In our reaction con-
ditions, when benzaldehyde was added to a vigorously stirred mixture of metallic Zn
and aluminium chloride hexahydrate in water and stirred for 16 h at room tempera-
ture, 80% of the corresponding vicinal diol was produced with good distereoselectiv-
ity. The reaction does not proceed with metallic Zn in water. It was also observed
that excess of aluminium chloride hexahydrate neither improves the yield nor
reduces the reaction time. The greatest yields were achieved when the molar ratio
of substrate to metal is 1:1.5, which is very impressive from the atom economy point
of view. Although several reagents are reported for this conversion, some of the
methods are effective for aldehydes only.[13,16] It was observed that an
electron-withdrawing group (entries 2, 5) reacts faster than an electron-donating
group (entries 4, 6, 10, and 11). Aromatic aldehydes and ketones having ortho sub-
stituents (entries 3 and 12) gave less yield than para and meta substituents. When the
coupling reaction was conducted with aromatic ketones (entries 7 and 9), only meso
compounds were formed. Aliphatic aldehydes or ketones are inert in our reaction
conditions. The absence of probable side products such as alcohol or olefin is the
additional advantage of the present synthetic approach as compared to other
reported methods.[14] Functional groups such as Cl, Br, and OMe were not affected.
Although the exact mechanism of the reaction cannot be proposed at this
stage, we believed that initially aluminium chloride hexahydrate forms a complex
with carbonyl compound, and metallic zinc transfer electrons to generate a ketyl
radical,[17] which dimerizes to form pinacol in water.
In conclusion, the present water-mediated and ecofriendly pinacol coupling
reaction has been achieved in good yield with improved distereoselectivity. However,
the beauty of this method is its milder reaction condition, use of commercially avail-
able cheapest reagent, and absence of side products. Newer synthetic transforma-
tions with this system are under study.
EXPERIMENTAL
Melting points were taken in open capillary tubes on a Buchi melting-point
1
apparatus and are uncorrected. H NMR (300 MHz, CDCl3) spectra were recorded

1090
B. K. HAZARIKA AND D. K. DUTTA
Table 1. Pinacol coupling reaction with carbonyl compound
SL no.
Substrate
Yield (%)
dl and meso (%)a
Time (h)
1
2
80
69:31
16
85
74
78
81
52:48
41:59
44:56
73:27
12
16
15
12
3
4
5
6
7
8
9
60
99
70
81
65:35
Meso
68:32
Meso
20
12
20
14
(Continued )

PINACOL COUPLING REACTION IN AQUEOUS MEDIA
1091
Time (h)
16
Table 1. Continued
SL no.
Substrate
Yield (%)
dl and meso (%)a
10
78
53:46
11
12
13
70
55
72
60:40
55:45
46:54
24
24
24
14
15
75
0
47:53
—
24
24
aThe ratio of dl=meso is determined by 1H NMR.
on an Bruker DPX (300-MHz) spectrometer, infared (IR) spectra were recorded on a
Perkin-Elmer (model 2000 series) instrument, and mass spectra were determined on a
Brucker Esquizer 3000 LC-MS instrument.
In a typical procedure, distilled benzaldehyde (1 mml) was added to a vigor-
ously stirred mixture of commercially available Zn (1.5 mmol) and AlCl3 Á 6H2O
(1 mmol) in 10 ml of water, and the mixture was stirred for 16 h at room temperature.
The reaction mixture was treated with HCl (3 M, 10 ml) and extracted with ethyl
acetate (2 Â 10 ml).The combined organic layer was washed with saturated solution
of NaHCO3 (10 ml) followed by brine (10 ml) solution and dried over anhydrous
Na2SO4. The filtrate was concentrated to obtain crude residues, which were purified
by column chromatography on silica gel with a mixture of ethyl acetate and hexane
(10%) to afford the desired diol in 80% yield. Similarly, all the compounds (entries
2–14) were prepared, and their reaction parameters are given in Table 1. All the
compounds show spectral data identical to those reported in the literatures.[14,16]

1092
B. K. HAZARIKA AND D. K. DUTTA
ACKNOWLEDGMENT
The authors thank Dr. P. G. Rao, director, Northeast Institute of Science and
Technology, for providing the necessary facilities for this work.
REFERENCES
1. (a) Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Ueno, H.; Nantermet, P. G.; Guy, R. K.;
Claiborne, C. F.; Renaud, J.; Couladouros, E. A.; Paulvannan, K.; Sorensen, E. J. Total
synthesis of taxol. Nature 1994, 367, 630–634; (b) Kim, Y. H. Dual enantioselective con-
trol in asymmetric synthesis. Acc. Chem. Res. 2001, 12, 955–962; (c) Kammermeier, B.;
Beck, G.; Jendralla, H.; Jacobi, D. Vanadium (II)- and niobium(III)-induced, diastereo-
selective pinacol coupling of peptide aldehydes to C2-symmetrical HIV-protease inhibi-
tors. Ang. Chem., Int. Ed. Eng. 1994, 33, 685–687.
2. Schreibmann, A. A. P. Amalgamated aluminium in methylene chloride as reducing agent:
A new convenient method for pinacolic reduction of aliphatic and cycloaliphatic ketones.
Tetrahedron Lett. 1970, 11, 4271–4272.
3. Namy, J. L.; Souppe, J.; Kagan, H. B. Efficient formation of pinacols from aldehydes or
ketones mediated by samarium diiodide. Tetrahedron Lett. 1983, 24, 765–766.
4. Honda, T.; Katoh, M. Trimethylsilyl chloride–accelerated reduction and pinacol coupling
of carbonyl compounds by means of samarium diiodide. Chem. Commun. 1997, 369–370.
ꢀ
5. Svatos, A.; Boland, W. Reductive pinacol coupling of aromatic carbonyl compounds
catalytic in chromium(II). Synlett 1998, 549–551.
6. Lipski, T. A.; Hilfiker, M. A.; Nelson, S. G. Ligand-modified catalysts for the McMurry
pinacol reaction. J. Org. Chem. 1997, 62(14), 4566–4567.
7. Khurana, J. M.; Sehgal, A.; Gogia, A.; Manian, A.; Maikap, G. C. Pinacolization and
reduction of aromatic carbonyls with aluminium–KOH. J. Chem. Soc., Perkin Trans. 1
1996, 2213.
8. (a) Groth, U.; Jeske, M. Diastereoselective Ce(III)-catalyzed pinacol couplings of alde-
hydes. Synlett 2001, 129–131; (b) Groth, U.; Jeske, M. Diastereoselective Ce(OiPr)3-
catalyzed pinacol couplings of aldehydes. Chem., Angew. Int. Ed. Eng. 2000, 39, 574–576.
9. (a) Bandini, M.; Cozzi, P.; Morganti, S.; Umani-Ronchi, A. Highly diastereoselective
pinacol coupling of aldehydes catalyzed by titanium–Schiff base complexes. Tetrahedron
Lett. 1999, 40, 1997–2000; (b) Li, Y.-G.; Tian, Q.-S.; Zhao, J.; Feng, Y.; Li, M.-J.;
You, T.-P. Asymmetric pinacol coupling of aromatic aldehydes catalyzed by a new
titanium–Schiff base complex. Tetrahedron: Asymmetry 2004, 15, 1707–1710.
10. Amato, I. The slow birth of green chemistry. Science 1993, 259, 1538–1541.
11. (a) Li, C.-J.; Chen, L. Organic chemistry in water. Chem. Soc. Rev. 2006, 35, 68–82; (b) Li,
C.-J. Organic reactions in aqueous media with a focus on carbonÀcarbon bond forma-
tions: A decade update. Chem. Rev. 2005, 105, 3095–3166; (c) Lindstrom, U. M. (Ed.).
Organic Reactions in Water: Principles, Strategies, and Applications; Wiley-Blackwell,
Oxford, UK, 2007; (d) Grieco, A. Organic Synthesis in Water; Thomson Sciences: London,
1998; pp. 129–133; (e) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.;
Sharples, K. B. ‘‘On water: Unique reactivity of organic compounds in aqueous suspen-
sion. Angew. Chem., Int. Ed. Eng. 2005, 44, 3275–3279; (f) Breslow, R. Hydrophobic effects
on simple organic reactions in water. Acc. Chem. Res. 1991, 24(6), 159–164.
12. Zhang, W.-C.; Li, C.-J. Magnesium-mediated carbonÀcarbon bond formation in aqueous
media: BarbierÀGrignard allylation and pinacol coupling of aldehydes. J. Org. Chem.
1999, 64, 3230–3236.
13. Xu, X.; Hirao, T. Vanadium-catalyzed pinacol coupling reaction in water. J. Org. Chem.
2005, 70, 8594–8596.

PINACOL COUPLING REACTION IN AQUEOUS MEDIA
1093
14. Wang, C.; Pan, Y.; Wu, A. InCl3=Al-mediated pinacol coupling reactions of aldehydes
and ketones in aqueous media. Tetrahedron 2007, 63, 429–434.
15. (a) Dutta, D. K.; Konwar, D. A new method for reductive coupling of carbonyl com-
pounds to olefins. Tetrahedron Lett. 2000, 41, 6227–6229; (b) Dutta, D. K. Aqueous
manganese-mediated reductive coupling of nitroarenes to azoxybenzenes. Synth. Com-
mun. 2006, 36, 1903–1906.
16. Li, C. J.; Meng, Y.; Ma, X. H. Y.; Chan, T. H. Manganese-mediated reactions in aqueous
media: Chemoselective allylation and pinacol coupling of aryl aldehydes. J .Org. Chem.
1997, 62, 8632–8633.
17. Trost, B. M. Ed. Comprehensive Organic Synthesis; Pergamen: New York, NY, 1991,
vol. III, 563–611.