A simple and straightforward approach toward selective C=C bond reduction by hydrazine

Article abstract of DOI:10.1139/v2012-057

A simple and straightforward method for reducing the C=C double bond with hydrazine is described. A number of representative C=C bonds in various steric and electronic environments were examined. Substituted alkenes can be selectively reduced in EtOH in the presence of hydrazine to give the corresponding products in up to 100% yields.

Full text of DOI:10.1139/v2012-057

758
A simple and straightforward approach toward
selective C=C bond reduction by hydrazine
Hao Chen, Jianmin Wang, Xuechuan Hong, Hai-Bing Zhou, and Chune Dong
Abstract: A simple and straightforward method for reducing the C=C double bond with hydrazine is described. A number
of representative C=C bonds in various steric and electronic environments were examined. Substituted alkenes can be selec-
tively reduced in EtOH in the presence of hydrazine to give the corresponding products in up to 100% yields.
Key words: hydrazine, reduction, C=C double bond.
Résumé : On décrit une méthode simple et directe de réduire une double liaison C=C à l’aide d’hydrazine. On a appliqué
la méthode à un certain nombre de doubles liaisons typiques, dans des environnements stériques et électroniques variés. Il
est possible de réduire sélectivement des alcènes substitués dans l’éthanol, en présence d’hydrazine, pour conduire aux pro-
duits correspondants avec des rendements allant jusqu’à 100 %.
Mots‐clés : hydrazine, réduction, double liaison C=C.
[Traduit par la Rédaction]
substitution of alkenes increases, the reaction becomes less
efficient and low conversion is observed. Obviously, these
methods provide improved results over traditional methods.
However, the limitation of scope and the presence of organo
or metal catalysts all preclude the straightforward approach to
selective C=C double bond reduction.8 Therefore, the devel-
opment of more efficient, commercial available, and simple
reducing agents is highly desirable.
To the best of our knowledge, there has not been a report
on the facile reduction of the C=C double bond by hydrazine
under mild conditions. Herein, we wish to report an unex-
pected reduction reaction of functionalized alkenes with com-
mercially available hydrazine under simple thermal
conditions that leads to a general and efficient method for se-
lective C=C double bond reduction of substituted alkenes.
Introduction
The reduction of functionalized alkenes is one of the most
fundamental reactions in organic chemistry.1 In recent deca-
des, various transition-metal catalysts such as Rh, Pt, and Pd
were generally applied for the selective reduction of alkenes
to the corresponding alkanes.2,3 Despite the important prog-
ress in this field, these reported processes not only had harsh
conditions and limited selectivity, but also produced signifi-
cant amounts of inorganic and organic wastes that are of en-
vironmental concern. Thus, the development of more
efficient, environmentally friendly, and economical nonmetal
reagents for selective reduction of functionalized alkenes is of
interest to the organic synthesis and medicinal chemistry
communities as well.
In contrast, diimide reduction appears to offer an attractive
solution, since NH=NH acts as a mild reducing agent for a
variety of unsaturated bonds.4,5 This reduction process has
the potential to be environmentally benign, since nitrogen
gas is the sole waste product. Imada et al.6 reported the first
green method for aerobic hydrogenation; the olefins can be
reduced by treatment with hydrazine in the presence of
FLEt·ClO4 under an O2 atmosphere to give the product in
excellent yields, with environmentally benign water and mo-
lecular nitrogen as the only waste products. o-Nitrobenzene-
sulfonylhydrazide (NBSH) is known to be another
convenient precursor of diimide, since the o-nitrobenzene sul-
finate is a good leaving group under mild conditions. In
2009, Marsh and Carbery7 demonstrated NBSH forming the
simple and efficient diimide alkene’s reductions protocol.
Meanwhile, it was also recognized that when the level of
Results and discussion
Our studies were initiated by the reaction of 2-allylphenol
1a with commercial hydrazine hydrate 2. The reaction was
carried out in air. To our delight, when 8 equiv of 2 was
used, 1a was fully converted to 2-propylphenol 3a (Table 1,
entry 7). As reasonably expected, no product was observed
when the reaction was run under an argon atmosphere (Ta-
ble 1, entry 10), which clearly indicates that diimide reduc-
tion occurred. After a brief survey of the reaction conditions,
it was found that solvents and the amount of hydrazine were
critical for the reaction efficiency (Table 1). 2-Allylphenol
was treated with 2 equiv of hydrazine in EtOH at 80 °C,
leading to trace amounts of the desired product after 14 h
(Table 1, entry 9). Further study indicated that a 34% yield
Received 27 June 2011. Accepted 6 July 2012. Published at www.nrcresearchpress.com/cjc on 30 August 2012.
H. Chen, J. Wang, X. Hong, H.-B. Zhou, and C. Dong. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan
University), Ministry of Education, State Key Laboratory of Virology, Wuhan University School of Pharmaceutical Science, Wuhan
430071, P.R. China.
Corresponding author: Chune Dong (e-mail: cdong@whu.edu.cn).
Can. J. Chem. 90: 758–761 (2012)
doi:10.1139/V2012-057
Published by NRC Research Press

Chen et al.
759
Table 1. Reduction of 2-allylphenol under various conditions.
Entry
1
2
3
4
5
6
7
2 (equiv)
Solvent
MeOH
H2O
CH3CN
THF
DCM
Toluene
EtOH
EtOH
EtOH
EtOH
Conversion (%)a
22
35
59
9
2
17
100
8
8
8
8
8
8
8
4
2
8
8
34
1
9
10b
No reaction
Note: Reaction conditions: 2-allylphenol (1a, 2 mmol), appropriate amount of hydrazine
hydrate (2), solvent, reflux 14 h.
1
aDetermined by H NMR analysis of the crude reaction mixture.
bThe reaction was run under an argon atmosphere.
of product was obtained when 4 equiv of 2 was employed
(Table 1, entry 8). Additionally, among the tested solvents,
ethanol was identified as the solvent of choice. Acetonitrile
gave an inferior result, but dichloromethane, THF, and tol-
uene were observed to be ineffective (Table 1, entries 1–6).
Having identified the optimal reaction conditions, we next
explored the scope and limitations of this reduction reaction
with hydrazine using various alkenes derivatives (1b–1r).
The results are summarized in Table 2. Clearly, our reduction
system proved rather effective for the selective reduction of a
wide variety of substituted alkenes, providing the correspond-
ing product in excellent yields. In addition to 2-allylphenol
1a, terminal alkenes 1b and 1c also reacted smoothly with
hydrazine giving the corresponding products in excellent
yields (Table 2, entries 2 and 3). Additionally, a polarized al-
kene, such as 1d, was efficiently reduced by hydrazine in
5.5 h, forming product 3d in excellent yield (Table 2, entry
4). Aromatic alkenes with the phenyl ring substituted with
an electron-donating or an electron-withdrawing group also
performed well in this reduction (Table 2, entries 5–13). For
example, p-methoxyl methyl cinnamate (1i) and p-trifluoro-
methyl cinnamic acid (1l) underwent smooth reduction (Ta-
ble 2, entries 9 and 12). It can be clearly seen that when the
level of th ealkene substitution increases, the reduction be-
comes less efficient. Tetra-substituted alkene 1r remained in-
ert under the same reaction conditions (Table 2, entry 18).
Interestingly, in the case of styrene, a 16% yield of enthyl-
benzene was obtained (Table 2, entry 17), which indicates
that, for mono-substituted alkenes, conjugation might play an
important role in hydrazine-promoted reduction.
fully applied to various substituted alkene reductions to form
the desired products in excellent yields. We believe this re-
duction method, from a synthetic point of view, is a valuable
alternative not only for the laboratory but also for industry.
Experimental section
General information
All reagents and solvents were obtained from commercial
sources and were used without further purification. The hy-
drazine hydrate used in this study was 80% solution. Column
chromatography was performed with silica gel (300–
400 mesh). NMR spectroscopy was performed on a Bruker
(400 MHz) spectrometer using TMS as the internal standard.
1
Products were characterized by comparison of their H NMR
spectroscopic data with those reported in the literatures.
General procedure for reduction reactions with hydrazine
hydrate
To 1 mmol of substrate 1 dissolved in 1.0 mL of solvent
was added 8 mmol of hydrazine 2 and the mixture was
heated to reflux for 5.5–24 h in air. After the reaction fin-
ished, the solvent was removed and the residue was extracted
three times with ethyl acetate (3 × 5 mL) and dried over
MgSO4. The product was characterized by NMR.
Acknowledgments
We are grateful to the Natural Science Foundation of
China (Grant Nos. 20972121, 81172935, and 91017005), the
Program for New Century Excellent Talents in University
(NCET-10-0625), and the Research Fund for the Doctoral
Program of Higher Education of China (20100141110021)
and the Science Foundation of Ministry of Education for the
New Teacher at the University of China (20090141120058)
for support of this research.
Clearly, this reduction system offers synthetic advantages
with respect to metal-catalyzed hydrogenation and other re-
ducing systems as well.
Conclusions
In conclusion, a simple, efficient, and highly selective
C=C double bond reduction protocol has been developed.
The hydrazine-mediated reducing system has been success-
References
(1) (a) March, J. Advanced Organic Chemistry: Reactions,
Published by NRC Research Press

760
Can. J. Chem. Vol. 90, 2012
Table 2. Scope of the reduction reactions promoted by hydrazine.
Entry
1
Substrate
Product
Yield (%)
100
2a
100
100
3a
4b
5b
6b
94
96
98
7b
8b
9b
96
95
98
10b
11a
92
100
Mechanism, and Structure; 4th ed.; John Wiley: Hoboken, NJ,
1992; (b) Larock, R. C. Comprehensive Organic Transforma-
tion: A Guide to Functional Group Preparations; Wiley-VCH:
Hoboken, NJ, 1999.
Bussolo, V.; Romano, M. R.; Favero, L.; Pineschi, M.; Crotti, P.
J. Org. Chem. 2006, 71 (4), 1696. doi:10.1021/jo051877p.
(3) (a) Mita, T.; Fukuda, N.; Roca, F. X.; Kanai, M.; Shibasaki, M.
Org. Lett. 2007, 9 (2), 259. doi:10.1021/ol062663c; (b) Åman,
J.; Jarevång, T.; Somfai, P. J. Org. Chem. 1996, 61 (23), 8148.
doi:10.1021/jo9612638; (c) Raspolli Galletti, A. M.; Bonac-
corsi, F.; Calvani, F.; Di Bugno, C. Catal. Commun. 2006, 7
(2) (a) Cui, X.; Burgess, K. Chem. Rev. 2005, 105 (9), 3272. doi:10.
1021/cr0500131; (b) Margathe, J. F.; Shipman, M.; Smith, S. C.
Org. Lett. 2005, 7 (22), 4987. doi:10.1021/ol051953a; (c) Di
Published by NRC Research Press

Chen et al.
Table 2..(concluded).
761
Entry Substrate
12b
Product
Yield (%)
>99
13b
>99
14b
15a
91
42
16a
17a
42
16
c
18
—
Note: Reaction conditions: 1 (5 mmol), hydrazine hydrate (2, 8 equiv), reflux in EtOH (5 mL), 14 h.
aReaction time was 24 h.
bReaction time was 5.5 h and the same result was observed in H2O.
cNo reaction.
(11), 896. doi:10.1016/j.catcom.2006.03.022; (d) Smit, C.;
Fraaije, M. W.; Minnaard, A. J. J. Org. Chem. 2008, 73 (23),
9482. doi:10.1021/jo801588d.
Desenko, S. M. J. Heterocycl. Chem. 2009, 46 (6), 1413. doi:10.
1002/jhet.218; (e) Haukaas, M. H.; O’Doherty, G. A. Org. Lett.
2002, 4 (10), 1771. doi:10.1021/ol025844x.
(4) (a) Hünig, S.; Müller, H. R.; Thier, W. Angew. Chem. Int. Ed.
Engl. 1965, 4 (4), 271. doi:10.1002/anie.196502711; (b) Pasto,
D. J.; Taylor, R. T. Organic Reactions; Vol. 40; John Wiley &
Sons: Hoboken, NJ, 1991, p 91; (c) Skouta, R.; Varma, R. S.;
Li, C. J. Green Chem. 2005, 7 (8), 571. doi:10.1039/b506881a.
(5) (a) Lee, B. K.; Sung, B. J.; Lee, W. K.; Yoon, D.-H.; Ha, H.-J.
Bull. Korean Chem. Soc. 2009, 30 (12), 3123. doi:10.5012/bkcs.
2009.30.12.3123; (b) Zibinsky, M.; Stewart, T.; Prakash, G. K.
S.; Kuznetsov, M. A. Eur. J. Org. Chem. 2009, 2009 (21), 3635.
doi:10.1002/ejoc.200900326; (c) Buszek, K. R.; Brown, N. J.
Org. Chem. 2007, 72 (8), 3125. doi:10.1021/jo0622173; (d)
Komykhov, S. A.; Ostras, K. S.; Kobzar, K. M.; Musatov, V. I.;
(6) Imada, Y.; Iida, H.; Naota, T. J. Am. Chem. Soc. 2005, 127 (42),
14544. doi:10.1021/ja053976q.
(7) Marsh, B. J.; Carbery, D. R. J. Org. Chem. 2009, 74 (8), 3186.
doi:10.1021/jo900237y.
(8) (a) Dhakshinamoorthy, A.; Alvaro, M.; Garcia, H. Adv. Synth.
Catal. 2009, 351 (14–15), 2271. doi:10.1002/adsc.200900362;
(b) Lacombe, P.; Castagner, B.; Gareau, Y.; Ruel, R.
Tetrahedron Lett. 1998, 39 (38), 6785. doi:10.1016/S0040-
4039(98)01490-7; (c) Myers, A. G.; Zheng, B. J. Am. Chem.
Soc. 1996, 118 (18), 4492. doi:10.1021/ja960443w; (d) Myers,
A. G.; Zheng, B. Tetrahedron Lett. 1996, 37 (28), 4841. doi:10.
1016/0040-4039(96)00965-3.
Published by NRC Research Press