Catalyst-free hydrogenation of alkenes and alkynes with hydrazine in the presence of oxygen

Article abstract of DOI:10.1055/s-0033-1340554

A series of alkenes and alkynes was subjected to reduction with hydrazine hydrate in ethanol in the presence of oxygen. An efficient method was developed for the reduction of C-C double bonds and C-C triple bonds with diimide, generated in situ from hydrazine hydrate by oxidation with oxygen. The reduction process proceeded for 24-48? hours with high chemoselectivity and excellent yields. This reduction procedure offers synthetic advantages over metal-catalyzed hydrogenation as well as other systems. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340554

LETTER
▌671
lCettaertalyst-Free Hydrogenation of Alkenes and Alkynes with Hydrazine in the
Presence of Oxygen
Reduction with Hydrazine
Nurettin Menges,a,b Metin Balci*a
a
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Fax +90(312)2103200; E-mail: mbalci@metu.edu.tr
b
Faculty of Pharmacy, Yüzüncüyil University, 65080 Van, Turkey
Received: 11.11.2013; Accepted after revision: 09.12.2013
used efficiently for hydrogen generation from aqueous
Abstract: A series of alkenes and alkynes was subjected to reduc-
hydrazine, for the reduction of nitroarenes.
tion with hydrazine hydrate in ethanol in the presence of oxygen. An
efficient method was developed for the reduction of C–C double
bonds and C–C triple bonds with diimide, generated in situ from hy-
drazine hydrate by oxidation with oxygen. The reduction process
proceeded for 24–48 hours with high chemoselectivity and excel-
lent yields. This reduction procedure offers synthetic advantages
over metal-catalyzed hydrogenation as well as other systems.
A range of C–C double bonds can be hydrogenated with
neutral flavin catalysts in the presence of 1–2 equivalents
of hydrazine under atmospheric O2.10 This is attributed to
diimide generation by the aerobic oxidation of hydrazine
with flavin derivatives rather than by direct reduction with
hydrazine. This finding led to the development of a mild
and convenient method for the aerobic reduction of ole-
fins.11 More recently, Kleinke and Jamison reported H2-
free hydrogenation of C–C double bonds via diimide gen-
erated from the new reagent combination of N,O-bistrifluo-
roacetyl-hydroxylamine and hydroxylamine.12
Key words: reduction, oxidation, hydrazine, hydrogenation, di-
imide
Hydrogenation of alkenes is an important reaction for the
synthesis of organic molecules. Alkenes react with hydro-
gen in the presence of a metal catalyst to give the corre-
sponding alkanes in a process that has been known since
the 19th century,1 however, there are many other methods
of effecting reduction.2 The transfer of hydrogen to
double bonds can be accomplished under either
heterogeneous3 or homogeneous4 conditions but, general-
ly, hydrogen is used with noble-metal catalysts, either
finely divided or supported on carriers. Commonly Pd, Pt,
and Rh are used as catalysts under very mild conditions
with reaction temperatures rarely exceeding 100 °C. The
catalyst can be easily removed from the reaction medium
by simple filtration. Homogeneous catalysts have exhibit-
ed high activity and selectivity with special applications,
and most homogeneous catalytic reactions, among them
enantioselective reactions, apply tertiary phosphines as
the most conventional ligands.5 Catalytic hydrogenation
requires special care in the handling of hydrogen (a highly
flammable and explosive gas) and, in some cases, rather
expensive catalysts and high pressures are needed for the
reaction to proceed.
Diimide is a short-lived intermediate that can be generated
by various methods. Besides the oxidation of hydrazine
with various reagents, diimide can be easily produced by
reaction of potassium azodicarboxylate and acetic acid in
methanol (Scheme 1).13 Benzenesulfonylhydrazide14 as
well
as
o-nitrobenzenesulfonyl-hydrazide
with
triethylamine15 have also recently been used as diimide
sources.
oxidation
AcOH
H N NH2
2
2
2 HN NH
diimide
KOOC N N
COOK
2
disproportionation
H2N NH2 + N2
Scheme 1 Generation of diimide
Diimide reduces alkenes and alkynes, resulting in the syn-
addition of hydrogen. This observation has led to the con-
clusion that the mechanism involves concerted hydrogen
transfer from cis-diimide to the substrate.17 Diimide re-
duction has advantages over classical reduction with hy-
drogen molecules. Studies show that diimide attacks trans
double bonds16 and strained double bonds18 more rapidly
than cis double bonds and unstrained double bonds. Fur-
thermore, diimide can reduce C–C double bonds in the
presence of weak oxygen–oxygen bonds19 as well as a di-
sulfide linkage (Scheme 2).
Hydrazine is an alternate and safe reactant for hydrogena-
tion, and the decomposition of hydrazine can result in the
formation of a range of products. Decomposition over
metals such as Pd and Pt tends to yield mostly nitrogen
and hydrogen, which can lead to hydrogenolysis of C–O
bonds6 and reduction of nitrobenzene derivatives to hy-
droxylamines in good yields.7 A highly active and selec-
tive nano-catalyst, Rh/HAP (rhodium supported on
hydroxy-apatite),8 as well as a Ni-Zr alloy9 have also been
In 1914, Falciola and Mannino reported that hydrazine re-
duces oleic acid to stearic acid.20 Later, in 1960, Cross21
communicated that gibberellic acid was smoothly
converted into tetrahydrogibberellic acid in hydrazine–
ethanol. Corey et al.22 generated diimide by either oxida-
SYNLETT 2014, 25, 0671–0676
Advanced online publication: 13.01.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340554; Art ID: ST-2013-D1049-L
© Georg Thieme Verlag Stuttgart · New York

672
N. Menges, M. Balci
LETTER
ceeded smoothly, giving the desired product 2 in 99%
yield (entry 3).
+
+
HN NH
HN NH
H2N
NH2
O
O
O
O
solvent, O2
1
2
Scheme 3 Reduction of styrene
O
HN NH
HN NH
+
+
O
O
O
We then examined a range of solvents under an oxygen at-
mosphere to improve the efficiency of the reaction (Table
1). The solvent was found to play an important role in the
system and the choice of solvent had a marked effect on
the yield. Reduction in tetrahydrofuran or dimethyl form-
amide was not complete after 24 hours (Table 1, entries 5
and 6). The reaction in ethanol (Table 1, entry 3) was com-
plete within 24 hours, but in methanol the yield was
slightly lower than that in ethanol (Table 1, entry 4).
S
S
S
S
Scheme 2 Reduction of double bonds by diimide
tion of hydrazine with air in the presence of copper ions
(trace) or with a hydrogen peroxide–copper ion (trace)
system and applied this to the reduction of various al-
kenes. More recently, Chen et al.23 described a reduction
protocol for C–C double bonds in which an eight-fold ex-
cess of hydrazine hydrate was used at the reflux tempera-
ture of various solvents. In the present communication, we
report that hydrazine hydrate reduces a range of alkenes
and alkynes smoothly at 35 °C in the presence of oxygen
without any catalyst or metal.
We further investigated the reduction potential of three
types of hydrazines; hydrazine monohydrate in ethanol,
hydrazine·HCl, and anhydrous hydrazine in THF. All re-
duction reactions were carried out in ethanol at 35 °C in
the presence of oxygen. Treatment of styrene with four
equivalents of hydrazine monohydrochloride in ethanol
for 24 hours resulted in a lower yield of 2 (9%, entry 7).
When the reaction was carried out with anhydrous hydra-
zine in THF (entry 8), GC-MS analysis of the reaction
mixture indicated the presence of 2 (69%) and 1 (31%). A
comparison of the reductions with three different hydra-
zines showed a dramatic difference in reactivity. There-
fore, we decided to continue the investigation with
hydrazine monohydrate in ethanol.
In the initial study, styrene (1) was used as the starting ma-
terial to examine the effect of solvent as well as the effect
of oxygen. The reaction was first carried out with four
equivalents of hydrazine hydrate in ethanol under a nitro-
gen atmosphere at 35 °C. After 24 hours only 10% of the
starting material had been reduced to ethylbenzene (2) and
90% of 1 was recovered (Scheme 3, Table 1, entry 1). We
assume that the oxygen dissolved in ethanol was respon-
sible for partial oxidation of hydrazine to diimide, which
then reduced the double bond. When the reaction was ex-
posed to air, ethylbenzene was formed in 71% yield after
24 hours (Table 1, entry 2). However, when the reaction
was carried out under oxygen, the transformation pro-
Under the optimized reaction conditions, we examined the
hydrogenation of 3a,4,7,7a-tetrahydro-1H-4,7-metha-
noindene (3; dicyclopentadiene) as a model system to test
the effect of strain on the hydrogenation reaction (Scheme
4). Hydrocarbon 3 contains two different double bonds in-
corporated into the bicyclic unit, with one being more
strained than the other. Treatment of 3 with four equiva-
Table 1 Optimization of Conditions for Reduction of Styrene (1) with Hydrazine
Entry
Reactant (4 equiv)
Solvent
Temp (°C)
Time (h)
Atmosphere
Yield (%)a
2
1
1
2
3
4
5
6
7
8
H2N–NH2·H2O
H2N–NH2·H2O
H2N–NH2·H2O
H2N–NH2·H2O
H2N–NH2·H2O
H2N–NH2·H2O
H2N–NH2·HCl
H2N–NH2 in THF
EtOH
EtOH
EtOH
MeOH
THF
35
35
35
35
35
35
35
35
24
24
24
24
48
24
24
24
N2
air
O2
O2
O2
O2
O2
O2
10
71
99
88
75
60
9
90
28
–
12
25
40
91
31
DMF
EtOH
EtOH
69
a Conversion and yields were determined by GC/MS analysis.
Synlett 2014, 25, 671–676
© Georg Thieme Verlag Stuttgart · New York

LETTER
Reduction with Hydrazine
673
lents of hydrazine monohydrate in ethanol for 24 hours re- Once the reaction conditions for this reduction had been
sulted in the formation of partly reduced hydrocarbon 4 in established, we examined the scope of the reaction by sub-
94% yield (Table 2, entry 1).
mitting a range of alkenes and alkynes to reduction with
hydrazine at 35 °C in ethanol; the results are summarized
in Table 3.
H2N NH2
+
Table 2 Reduction of 3 with Hydrazinea
EtOH, O2, 35 °C
3
4
6
5
Entry
Reactant
Time (h)
Yield 4/5 (%)
not observed
1
2
3
4
5
6
7
8
H2NNH2·H2O
H2NNH2·H2O
H2NNH2·H2O
H2NNH2·H2O
H2NNH2·H2O
H2NNH2·H2O
H2NNH2·H2O
H2NNH2·H2O
24
48
94:1
85:15
62:38
52:48
32:68
14:86
13:87
13:87
Scheme 4 Reduction of hydrocarbon 3
65
The starting material was consumed and fully reduced
product 5 was formed in only 1% yield. The reactivity dif-
ferences of the two double bonds in 3 can be attributed to
the difference in bond angle strain, with the more strained
olefin reacting more rapidly.24 When the reaction time
was increased to 48 hours, the amount of 5 increased to
15% (Table 2, entry 2). By screening for the influence of
time on product yield, we found that the amount of fully
reduced product 5 could be increased to 87% (Table 2, en-
tries 3–8). To complete the reduction, the addition of fur-
ther hydrazine hydrate was necessary. Product 6 was not
formed.
72
92
118
137
144
a All reactions were carried out under an oxygen atmosphere in EtOH
at 35 °C.
Table 3 Reduction of Alkenes and Alkynes
Entry
Alkene or Alkyne
Product
Time (h)
18
Yield (%)a
95
1
7
8
2
52
94
9
10
12
14
16
3
4
5
24
47
24
>98
11
76b,25
13
O
O
>9926
15
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 671–676

674
N. Menges, M. Balci
LETTER
Table 3 Reduction of Alkenes and Alkynes (continued)
Entry
Alkene or Alkyne
Product
Time (h)
Yield (%)a
N
N
HO
HO
6
25
>9927
N
N
17
18
7
8
36
90
19
2
Ph
Ph
Ph
Ph
Ph
144
12/86b,c,28
20
21
Ph
22
O
O
9
48
95/5
24
23
OH
25
O
O
N
N
10
11
38
39
>99
26
28
27
N
N
O
N
N
N
O
O
98
29
OH
12
36
89b
OH
30
31
a Conversion and yield were determined by GC/MS analysis.
b Consumption of 13, 20 and 30 was 77, 70, and 80%, respectively.
c Yield based on consumed starting material.
First we submitted a range of alkenes (7, 9, 11, 13, 15, and corresponding reduced products (8, 10, 12, 14, 16, and 18)
17) to reduction with diimide. In all cases, after 18– were formed in excellent yields (Table 3, entries 1, 2, 4, 5,
52 hours, the starting materials were consumed and the and 6). In the case of 13, the reduction was sluggish com-
Synlett 2014, 25, 671–676
© Georg Thieme Verlag Stuttgart · New York

LETTER
Reduction with Hydrazine
675
(4) (a) Cui, X.; Burguess, K. Chem. Rev. 2005, 105, 3272.
pared to the other systems, however, the yield based on
the consumed product was also excellent. The decreased
reactivity was attributed to the steric hindrance around the
double bond in 13. The reduction of acetylene derivatives
also proceeded smoothly in the presence of oxygen, giv-
ing the corresponding products in high yields.
(b) Handbook of Homogeneous Hydrogenation; de Vries, J.
G.; Elsevier, C. J., Eds.; Wiley-VCH: Weinheim, 2007.
(5) (a) Kollar, L.; Keglevich, G. Chem. Rev. 2010, 110, 4257.
(b) Alonso, F.; Riente, P.; Yus, M. Tetrahedron 2009, 65,
10637.
(6) Furst, A.; Berlo, R. C.; Hooton, S. Chem. Rev. 1965, 65, 51.
(7) Zhang, Y.; Chakraborty, M.; Cerda-Smith, C. G.; Bratton, R.
N.; Maurer, N. E.; Senser, E. M.; Novak, M. J. Org. Chem.
2013, 78, 6992.
(8) Huang, L.; Luo, P.; Pei, W.; Liu, X.; Wang, Y.; Wang, J.;
Xing, W.; Huang, J. Adv. Synth. Catal. 2012, 354, 2689.
(9) Nozaki, A.; Kamegawa, T.; Ohmichi, T.; Yamashita, H.
ChemPhysChem 2013, 14, 2534.
(10) Imada, Y.; Kitagawa, T.; Ohno, T.; Iida, H.; Naota, T. Org.
Lett. 2010, 12, 32.
(11) (a) Imada, I.; Iida, H.; Kitagawa, T.; Naota, T. Chem. Eur. J.
2011, 17, 5908. (b) Lamani, M.; Guralamata, R. S.; Prabhu,
K. R. Chem. Commun. 2012, 48, 6583.
(12) Kleinke, A. S.; Jamison, T. F. Org. Lett. 2013, 15, 710.
(13) (a) Hünig, S.; Müller, H. R.; Thier, W. Angew. Chem. Int.
Ed. 1965, 4, 271. (b) Miller, E. C. J. Chem. Educ. 1965, 42,
254.
(14) Cusack, N. J.; Reese, C. B.; Risius, A. C.; Roozpeikar, B.
Tetrahedron 1976, 32, 2157.
(15) Haukaas, M. H.; O’Doherty, G. A. Org. Lett. 2002, 4, 1771.
(16) Hünig, S.; Müller, H. R. Angew. Chem. 1962, 74, 215.
(17) Van Tamelen, E. E.; Dewey, R. S.; Lease, M. F.; Pirkle, W.
H. J. Am. Chem. Soc. 1961, 83, 4302.
(18) Sutbeyaz, Y.; Secen, H.; Balci, M. J. Org. Chem. 1988, 53,
2312.
(19) (a) Balci, M. Chem. Rev. 1981, 81, 91. (b) Coughlin, D. J.;
Brown, R. S.; Salomon, R. G. J. Am. Chem. Soc. 1979, 101,
1533. (c) Adam, W.; Eggelte, H. J. J. Org. Chem. 1977, 42,
3987.
(20) Falciola, P.; Mannino, A. Ann. Chim. Appl. 1914, 2, 351.
(21) Cross, B. E. J. Chem. Soc. 1960, 3022.
(22) Corey, E. J.; Mock, W. L.; Pasto, D. J. Tetrahedron Lett.
1961, 347.
(23) Chen, H.; Wang, J.; Hong, X.; Zhou, H.-B.; Dong, C. Can.
J. Chem. 2012, 90, 758.
(24) Garbish, E. W. Jr.; Schildtcrout, S. M.; Patterson, D. P.;
Sprecher, C. M. J. Am. Chem. Soc. 1965, 87, 2932.
(25) Simakova, I. L.; Solkina, Y.; Deliy, I.; Warna, J.; Murzin, D.
Y. Appl. Catal., A 2009, 356, 216.
Reduction of phenylacetylene (19; Table 3, entry 7) was
completed in 36 hours in 90% of yield. However, diphen-
ylacetylene (20) was much less reactive than phenylacet-
ylene, and its reaction with hydrazine was not complete
after 144 hours (Table 3, entry 8), with only 70% of the
starting material consumed. 1,2-cis-Diphenylethene (21)
and 1,2-diphenylethane (22) were formed in a ratio of
12:86. The cis-configuration of diphenylethene was deter-
mined with the help of 13C NMR satellite peaks;29 the vic-
inal coupling in the ethylene unit was found to be 12.2 Hz.
3
In styrene, cis-coupling has a value of J = 10.9 Hz,
whereas trans-coupling 3J = 17.6 Hz.30 This finding sup-
ports further the proposed cis-reduction and formation of
diimide as the reducing agent. Prop-2-yn-1-yloxy-ben-
zene (23) showed similar reactivity to that of phenylacet-
ylene, giving propoxybenzene (24) in 95% yield (Table 3,
entry 9); in this case, phenol was also formed as a by-
product (5%) arising from reduction of the C–O bond. 1-
[(1-(Prop-2-yn-1-yl)-1H-pyrrol-2-yl)]ethanone (26) was
also smoothly reduced to N-propyl derivative (27; Table
3, entry 10). However, the corresponding aldehyde 28 re-
acted first with hydrazine to give the diazine derivative
(Table 3, entry 11), followed by reduction of the propar-
gyl groups to give the final product 29. Finally, p-benzo-
quinone (30) underwent smooth reduction to form
hydroquinone (31) in 89% yield.
In conclusion, the scope of hydrazine reduction in the
presence of oxygen has been studied in detail.31 We as-
sume that the diimide formed initially is responsible for
reduction of the C–C double bonds. This method provides
a simple and selective reduction protocol of double bonds
as well as alkynes and offers advantages over metal-cata-
lyzed hydrogenation and other reducing systems.
(26) Mirsadeghi, S.; Rickborn, B. J. Org. Chem. 1985, 50, 4340.
(27) Wu, H.; Hintermann, L. Synthesis 2013, 45, 888.
(28) Broggi, J.; Jurcik, V.; Songis, O.; Poater, A.; Cavallo, L.;
Slawin, A. M. Z.; Cazin, C. S. J. J. Am. Chem. Soc. 2013,
135, 4588.
Acknowledgment
We are indebted to the Scientific and Technological Research
Council of Turkey (TUBITAK, Grant No. TBAG-112 T360), the
Middle East Technical University, and the Turkish Academy of
Sciences (TUBA) for financial support of this work. N.M. is grate-
ful for a scholarship provided by BIDEB-TUBITAK.
(29) Balci, M. Basic 1H and 13C NMR Spectroscopy; Elsevier:
Amsterdam, 2005, 330.
(30) Reynolds, W. F.; Peat, I. R.; Hamer, G. K. Can. J. Chem.
1974, 52, 3415.
(31) Procedure for hydrogenation: A round-bottom flask was
charged with alkene or alkyne (1 mmol) and EtOH (1 mL)
[except for cinchonine (3 mL) because of its lower
solubility]. To this mixture was added hydrazine
monohydrate (4 mmol), then the reaction was placed under
an atmosphere of oxygen (balloon). The resulting mixture
was stirred at 35 °C for the appropriate time. After
consumption of the starting material, the solvent was
removed under vacuum and the residue was extracted with
EtOAc. The organic phase was dried over MgSO4 (for
isolated products). Volatile products were not isolated and
they were analyzed directly by using GC-MS.
References and Notes
(1) Mattson, B.; Foster, W.; Greimann, J.; Hoette, T.; Le, N.;
Mirich, A.; Wankum, S.; Cabri, A.; Reichenbacher, C.;
Schwanke, E. J. Chem. Educ. 2013, 613; and references
therein.
(2) Bond, G. Metal Catalysed Reactions of Hydrocarbons;
Springer: New York, 2005.
(3) Nishimura, S. Handbook of Heterogeneous Catalytic
Hydrogenation for Organic Synthesis; John Wiley & Sons:
New York, 2001.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 671–676

676
N. Menges, M. Balci
LETTER
1,2,3,4-Tetrahydro-1,4-epoxynaphthalene (16):26 1
H
150.4, 126.5, 125.9, 116.1, 107.4, 49.2, 23.3, 9.7; IR: 2957,
2921, 2856, 1619, 1522, 1460, 1416, 1402, 1368, 1295,
1213, 1065. HRMS: m/z [M + H]+ calcd for C16H23N4:
271.1923; found: 271.1905.
NMR (400 MHz, CDCl3): δ = 7.16–7.13 (m, AA′ of AA′BB′,
2 H), 7.09–7.06 (m, BB′ of AA′BB′, 2 H), 5.32 (dd, J = 3.0,
1.8 Hz, 2 H), 2.01–1.95 (m, AA′ of AA′BB′, 2 H), 1.32–1.27
(m, BB′ of AA′BB′, 2 H). 13C NMR (100 MHz, CDCl3): δ =
145.6, 126.5, 118.7, 78.9, 26.6.
1-(1-Propyl-1H-pyrrol-2-yl)ethanone (27):32 Isolated
yield: 91%; dark-brown viscous liquid. 1H NMR (400 MHz,
CDCl3): δ = 6.96 (dd, J = 4.0, 1.6 Hz, 1 H), 6.85 (app t, J =
2.5 Hz, 1 H), 6.12 (dd, J = 4.0, 2.5 Hz, 1 H), 4.27 (t, J =
7.2 Hz, 2 H), 2.43 (s, 3 H), 1.75 (hext, J = 7.2 Hz, 2 H), 0.89
(t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 188.2,
130.2, 130.1, 120.2, 107.8, 51.4, 27.3, 24.6, 11.0.
(32) Goldberg, Y.; Abele, E.; Shymanskaya, M. Synth. Commun.
1991, 21, 557.
(1E,2E)-1,2-Bis[(1-propyl-1H-Pyrrol-2-
yl)methylene]hydrazine (29): Obtained as a pale-orange
viscous liquid that was recrystallized from MeOH to give a
yellow powder (mp 59–60.5 °C). Isolated yield: 89%. 1H
NMR (400 MHz, CDCl3): δ = 8.40 (br, 2 H), 6.75 (app. t,
J = 2.1 Hz, 2 H), 6.56 (br s, 2 H), 6.11 (dd, J = 3.7, 2.6 Hz,
1 H), 4.24 (t, J = 7.2 Hz, 4 H), 1.75 (hext, J = 7.2 Hz, 4 H),
0.85 (t, J = 7.2 Hz, 6 H). 13C NMR (100 MHz, CDCl3): δ =
Synlett 2014, 25, 671–676
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.