this technique to the synthesis of a wide range of materials,
it is necessary to develop new molecular compounds
that have weak intramolecular bonds while maintaining
reactivity.
Table 1. Reaction of Hydrazines with 2-Methoxycinnamalde-
hyde (2a)a
Scheme 1. Formation of Azines by the Solid State Reactions of 1
with Carbonyl Compounds
hydrazine
(mmol)
temp time
yield
entry
1
solvent (°C) (h) product (%) remark
1
no
no
25 <20 3a only >97b yellow
(5.0 mmol)
1
crystal
2
3
4
60
<3 3a only >97b yellow
(50.0 mmol)
crystal
Very recently, we isolated the hydrazinium carboxylate
(H3NþNHCO2ꢀ, 1) under supercritical CO2 conditions as
a crystallinesolid, which can be regardedasa newsynthetic
alternative to liquid hydrazine (NH2NH2).5 Reported
herein is the solid-state reactivity of solid hydrazine (1)
toward various carbonyl compounds such as aldehydes
and ketones. An important feature is that the azine deri-
vatives were readily prepared in the absence of solvent
using simple grinding. Moreover, the solid-state reaction
shows high selectivity, which yields over 97% of the
product and does not generate any waste other than water
and CO2 (Scheme1).
H2NNH2-xH2O ether 25
5
2
3a þ
∼75c,d
(5.0 mmol) (10 mL)
unknown
3a þ
H2NNH2-xH2O
no
25
<40c,e
(10.0 mmof)
unknown
a 2-Methoxycinnamaldehyde(2a)/hydrazine = 2/1. b Isolated yield
based on 1 (hydrazinium carboxylate, H3NþNHCO2ꢀ) was determined
using 1H NMR. c Not isolated, the yield is based on 1H NMR. d Product-
(s) resulting from the reaction(s) at the olefin group in 2a with possible
hydrazine formation. The starting aldehyde, 2a, is detected, which is ca.
13%. e Highly exothermic. Product(s) resulting from the reaction(s) at
the olefin group in 2a with possible hydrazine formation. The starting
aldehyde, 2a, is detected, which is ca. 48%.
Azines exhibit interesting optical,6 biological,7 and
conductive8 properties and are extensively used as syn-
thetic intermediates.9 Typically, azines are prepared by
reacting 2 equiv of a carbonyl compound with 1 equiv of
the product.3d Unlike the hydrazinium salt,3b,c our solid
hydrazine (1) dissociates into hydrazine and CO2.
Therefore, the solid-state reactions of aldehydes or
ketones with 1 using the simple grinding method did not
require further separation. The reaction is a single-step
process, and the evolution of CO2 gas stimulates the
forward reaction to produce the desired azine complexes.
This is the first report on the waste-free synthesis of azine
derivatives using solid-state grinding under ambient con-
ditions, which also provides a novel green approach for
preparing various azines on a large scale and in the absence
of solvents. Notably, the solid-state reaction provides new
opportunities for large-scale production in a small vessel:
for example, the current system was scaled to prepare more
than 16 g of the azine product within a 50 mL vial (see
Table 1, entry 2).
A 1:2 mixture of 1 and an aromatic aldehyde (Table 1,
entry 1) was ground at room temperature using a
mortar and pestle.10 The physical grinding resulted in
a distinctive color change from white to yellow within 5
min. The ground powder was placed in a vial without
any agitation. Near-complete conversion to an azine
compound (3a) with the formula C20H20N2O2 was
achieved within 20 h; the process was carefully mon-
itored using both powder X-ray diffraction (XRD) and
1H NMR spectroscopy. The solid-state reaction was
complete within 2 h at a reaction temperature of 60 °C.
hydrazine hydrate (NH2NH2 H2O) in solution under re-
3
fluxing conditions or with promoters such as acid or iodine.
The solution reaction proceeds rapidly but often yields
byproducts, which require product separation.3,6a,7a,8a,9a
As an alternative, Kaupp and Schmeyers employed
hydrazine-hydroquinone powder as a source of hydra-
zine; the powder was ball-milled with a solid carbonyl
compound to yield an azine product. Although the
mechanochemical reaction was carried out in the solid
state, it called for the elimination of hydroquinone from
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(10) Precaution. The solid hydrazine, hydrazinium carboxylate (1),
could be harmful for health due to its sublimation character. The
equipment of effective ventilation is highly recommended for handling
the solid hydrazine to avoid vapor inhalation.
Org. Lett., Vol. 13, No. 24, 2011
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