Palladium-catalyzed deprotection of hydrazones to carbonyl compounds

Article abstract of DOI:10.1055/s-1999-3623

Hydrazones of ketones and aldehydes undergo facile cleavage to the corresponding carbonyl compounds by a catalytic amount of Pd(OAc)₂/SnCl₂ in good yields.

Full text of DOI:10.1055/s-1999-3623

2
024
SHORT PAPER
Palladium-Catalyzed Deprotection of Hydrazones to Carbonyl Compounds
a
b
b
b
Takashi Mino, Tatsuya Hirota, Noriko Fujita, Masakazu Yamashita*
aDepartment of Materials Technology, Faculty of Engineering, Chiba University, Inage, Chiba 263-8522 Japan
Fax +81(43)2903401; E-mail: tmino@planet.tc.chiba-u.ac.jp
bDepartment of Molecular Science and Technology, Faculty of Engineering, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan
Fax +81(77)4656840; E-mail: myamashi@mail.doshisha.ac.jp
Received 21 June 1999; revised 27 August 1999
This work reports the cleavage of hydrazones by Pd-cata-
Abstract: Hydrazones of ketones and aldehydes undergo facile
lyst. Representative results of the cleavage of aromatic,
cleavage to the corresponding carbonyl compounds by a catalytic
unsaturated, alicyclic and aliphatic ketone dimethylhydra-
amount of Pd(OAc) /SnCl in good yields.
2
2
8
zones are listed in Table 1. When acetophenone dimeth-
Key words: hydrazones, aldehydes, ketones, palladium acetate,
tin(II) chloride
ylhydrazone 1a was treated with a catalytic amount of
Pd(OAc) and SnCl as a co-catalyst in DMF/H O at 70 °C
2
2
2
under an air atmosphere, the hydrolyzed compound ace-
tophenone was obtained in good yield (Entry 1). Howev-
er, when this reaction was carried out under an Ar
atmosphere, acetophenone was obtained only in 48%
yield after 96 h. When water was absent in this reaction,
Hydrazones have been found to be one of the most useful
synthetic precursors of aldehydes and ketones. In this
1
method, a key point is the cleavage of the hydrazone moi-
ety to the carbonyl group. Previously, a variety of such
methods have been reported, including oxidative cleavage
1
a was not cleaved after 48 h under an air atmosphere, but
when the reaction was carried out at 130 °C under the
same conditions, the corresponding ketone was obtained
in 27% yield after 24 h. Therefore, we believe that this re-
action proceeded competitively by acidic and oxidative
mechanisms. One of the characteristics of this reaction is
that it proceeds under mild conditions without using sto-
ichiometric acidic reagents or oxidative reagents. As
shown in Entry 2, even a,b-unsaturated ketone dimethyl-
hydrazone 1b was hydrolyzed without rearrangement of
the a,b double bond using this Pd(OAc) /SnCl catalytic
2
by ozonolysis at low temperature, N-methylation of the
hydrazone using methyl iodide followed by hydrolysis in
3
a biphasic aqueous HCl–pentane system, and copper-cat-
4
alyzed hydrolysis. The ozonolysis method provides near-
ly quantitative chemical yields under neutral conditions
and short reaction times, but this method cannot be used if
there are other ozone-sensitive groups such as alkenes in
the molecule. Many other reagents have been used to
cleave hydrazones and to regenerate carbonyl compounds
5
2
2
from their N,N-dialkylhydrazones. However, these meth-
system. Functional groups such as the halogen or nitro
group were also inert with this catalyst, and no by-product
was observed by GLC (Entries 5 and 6).
ods require a stoichiometric or excess amount of cleavage
reagents. The catalytic method of cleavage has only been
6
reported using bismuth catalysis. Therefore, we were in-
The cleavage of benzylacetone hydrazones 2, which de-
rived from various N,N-bissubstituted hydrazines such as
N,N-methylphenylhydrazine, N,N-dibenzylhydrazine, 1-
aminohomopiperidine and N-aminomorpholine, proceed-
ed easily with good yields (Table 2). When the cleavage
of hydrazone 2a was carried out, N-nitroso-N-methyl-
aniline was identified using GLC by comparison of the re-
tention time with those of authentic samples.
terested in the catalytic methods of hydrazone cleavage.
In the course of our study using palladium catalyst in or-
ganic synthesis, we found that palladium acetate is effec-
7
tive for the catalytic cleavage of hydrazones 1–3
(
Scheme).
R3
The results of the cleavage of various aldehyde dimethyl-
hydrazones 3 are listed in Table 3. When octanal dimeth-
ylhydrazone 3a was reacted using this catalyst system for
6 h, octanal was obtained as the main product (Table 3,
Entry 1). However, when this reaction was carried out for
N
N
R4
O
Pd(OAc) –SnCl
2
2
DMF–H O
R1
R2
2
R1
R2
1
- 3
2
4 h, octanoic acid was obtained as the main product in-
1
2
3
: R = alkyl, aryl; R = alkyl, aryl; R = R = Me
1
2
3
4
stead of the corresponding aldehyde (Entry 2). Conse-
quently, it was necessary to optimize the reaction time. As
shown in Entry 4, the a,b-unsaturated aldehyde dimethyl-
hydrazone 3c was cleaved slowly without the formation of
the corresponding acid. Dimethylhydrazone 3d, which
was prepared from an air-sensitive aldehyde, gave a mix-
ture of the corresponding aldehyde and acid (Entries 5 and
: R = PhCH CH ; R = Me; R = alkyl, aryl; R =alkyl
1
2
2
2
3
4
: R = alkyl; R = H; R = R = Me
1
2
3
4
Scheme
6
).
Synthesis 1999, No. 12, 2024–2026 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Palladium-Catalyzed Deprotection of Hydrazones to Carbonyl Compounds
2025
Table 1 Pd(OAc)2 / SnCl2-Catalyzed Cleavage of
Dimethylhydrazone 1
Table 2 Pd(OAc)2 / SnCl2-Catalyzed Cleavage of 4-Phenyl-2-butanone
Hydrazone 2
Yield (%)a,b
Entry
Hydrazone 2
Time (h)
Yield (%)a
Entry
1
Hydrazone 1
NNMe2
Time (h)
24
Me
N
1a
1b
1c
1d
1e
1f
90(75)
N
Ph
Bn
1
2a
2b
24
93
NNMe2
2
3
4
5
6
72
48
24
24
24
(53)c
>98
98
Bn
N
N
NNMe2
2
24
>98
N
N
NNMe2
NNMe2
NNMe2
N
N
3
4
2c
2d
24
24
>98
>98
O
>98
>98
Cl
a
GLC yields.
O2N
NNMe2
7
1g
72
>98
Table 3 Pd(OAc)2 / SnCl2-Catalyzed Cleavage of Aldehyde
Dimethylhydrazone 3
Entry
Hydrazone 3
Time (h) Yield (%)a,b
NNMe2
8
9
1h
1i
24
48
96
94
NNMe2
1
2
6
87(6)
3a
NNMe2
24
24(75)
a
GLC yields.
NNMe2
b
c
Values in parentheses are isolated yields.
mol% of Pd(OAc)2 and 2.5 mol% of SnCl2 were used.
5
3
4
3b
3c
6
76
14
NNMe2
Cyclic thioacetals and ketals can also be used as carbonyl
protecting groups instead of hydrazone. Therefore, we
24
5
investigated the deprotection of a cyclic thioketal such as
NNMe2
5
6
6
44(13)
53(47)
S
S
3d
24
a
GLC yields.
b
Values in parentheses are GLC yields of the correspounding acids.
4
Synthesis 1999, No. 12, 2024–2026 ISSN 0039-7881 © Thieme Stuttgart · New York

2
026
T. Mino et al.
SHORT PAPER
+
1
,3-dithiolane of 4-phenyl-2-butanone 4. However, 4 was GC-MS: m/z (%) = 140 (M , 13), 125 (7), 83 (100), 69 (59), 55 (46).
not cleaved to the corresponding ketone even though the Octan-2-one
1
reaction with Pd(OAc) /SnCl catalyst was carried out for
H NMR: d = 0.88 (t, J = 6.7 Hz, 3H), 1.28 (br, 6H), 1.54-1.61 (m,
2
2
2
H), 2.14 (s, 3H), 2.42 (t, J = 7.2 Hz, 2H).
1
20 h. Therefore, this Pd-catalyst shows chemoselectivity
+
between 1,3-dithiolane and hydrazone moieties.
GC-MS: m/z (%) = 128 (M , 3), 113 (3), 85 (60).
In conclusion, a Pd(OAc) /SnCl catalyst has been suc- Menthone:
2
2
1
H NMR: d = 0.85 (d, J = 7.0 Hz, 3H), 0.91 (d, J = 7.0 Hz, 3H), 1.01
cessfully used for the cleavage of hydrazones to the corre-
sponding carbonyl compounds.
(
(
d, J = 6.4 Hz, 3H), 1.32-1.40 (m, 2H), 1.88-2.15 (m, 6H), 2.33-2.37
m, 1H).
+
GC-MS: m/z (%) = 154 (M , 17), 112 (70), 69 (100), 55 (98).
All carbonyl compounds, hydrazines were obtained from commer-
cial sources. The isolated carbonyl compounds or crude products
were identified by H NMR (400 MHz) and GC-MS or GLC by
Octanal
+
GC-MS: m/z (%) = 100 (M -28, 5), 84 (30), 74 (58), 59 (100).
1
comparison of the t with those of authentic samples. Hydrazones
Octanoic Acid
R
+
1
-3 were prepared from the corresponding carbonyl compounds.
GC-MS: m/z (%) = 115 (M -29, 3), 101 (11), 74 (47), 60 (100).
N,N-dimethylhydrazine, N,N-methylphenylhydrazine, N,N-diben-
zylhydrazine, 1-aminohomopiperidine and N-aminomorpholine
were prepared according to the standard method. Dithiolane 4 was
Citronellal
+
GC-MS: m/z (%) = 154 (M , 4), 139 (5), 121 (38), 111 (13), 69
9
(
100).
prepared from benzylacetone and 1,2-ethanedithiol according to the
standard method. 1
solutions.
0,11
1
H NMR spectra were obtained on CDCl3
Citral
+
GC-MS: m/z (%) = 152 (M , 2), 137 (4), 123 (4), 109 (6), 69 (100).
Cyclohexanecarboxaldehyde
+
Deprotection of 1–4;Typical Procedure
GC-MS: m/z (%) = 112 (M , 3), 83 (28), 74 (54), 59 (100).
A solution of hydrazone (1.0 mmol) in DMF (2 mL) was added to a
soln of Pd(OAc) (0.02 mmol) and SnCl (0.01 mmol) in H O (2
mL). The reaction mixture was stirred at 70 °C for 24 h and then di-
Cyclohexanecarboxylic Acid
GC-MS: m/z (%) = 128 (M , 3), 110 (2), 99 (3), 83 (25), 55 (100).
+
2
2
2
luted with EtOAc, washed with brine, and dried (MgSO ). Evapo-
4
ration of the solvents and bulb-to-bulb distillation or silica gel References and Notes
column chromatography gave the pure carbonyl compounds.
(
1) Bergeiter, D. E.; Momongan, M. In Comprehensive Organic
Synthesis, Vol. 2; Heathcock, C. H., Ed.; Pergamon: Oxford,
991; p 503 and references cited therein.
Acetophenone
1
H NMR: d = 2.61 (s, 3H), 7.45-7.97 (m, 5H).
1
+
GC-MS: m/z (%) = 120 (M , 26), 105 (100), 77 (90), 51 (39).
(2) Erickson, R. E.; Andrulis, P. J. Jr.; Collins, J. C.; Lungle,M.
L.; Mercer, G. D. J. Org. Chem. 1969, 34, 2961.
3) (a) Sisler, H. H.; Omietanski, G. M.; Rudner, B. Chem. Rev.
bp: 65-67°C / 5 Torr.12
(
Isophorone
1957, 57, 1021.
1
H NMR: d = 1.04 (s, 6H), 1.94 (s, 3H), 2.17 (s, 2H), 2.20 (s, 2H),
(b) Avaro, M.; Levisalles, J.; Rudler, H. J. Chem. Soc., Chem.
Commun. 1969, 445.
7
.28 (s, 1H).
+
(4) (a) Corey, E. J.; Knapp, S. Tetrahedron Lett. 1976, 3667.
b) Mino, T.; Fukui, S.; Yamashita, M. J. Org. Chem. 1997,
2, 734.
GC-MS: m/z (%) = 138 (M , 14), 82 (100).
(
6
4
-Phenylbutan-2-one
1
H NMR: d = 2.14 (s, 3H), 2.75-2.78 (m, 2H), 2.88-2.91 (m, 2H),
7
(
5) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3ed.; Wiley: New York, 1999.
(b) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart,
1994.
.14-7.30 (m, 5H).
+
GC-MS: m/z (%) = 148 (M , 68), 105 (100), 91 (78), 77 (32) and 51
28).
(
(
6) Boruah, A.; Baruah, B.; Prajapti, D.; Sandhu, J. Synlett 1997,
1251.
7) (a) Ohishi, T.; Yamada, J.; Inui, Y.; Sakaguchi, T.; Yamashita,
M. J. Org. Chem. 1994, 59, 7522.
Propiophenone
1
H NMR: d = 1.23 (t, J = 7.3 Hz, 3H), 3.01 (q, J = 7.3 Hz, 2H), 7.44-
(
7
.48 (m, 2H), 7.53-7.57 (m, 1H), 7.96-7.98 (m, 2H).
+
GC-MS: m/z (%) = 134 (M , 12), 105 (100), 77 (59) and 51 (28).
(
b) Ohishi, T.; Tanaka, Y.; Yamada, J.; Tago, H.; Tanaka, M.;
Yamashita, M. Appl. Organomet. Chem. 1997, 11, 941.
(8) Mino, T.; Hirota, T.; Yamashita, M. Synlett 1996, 999.
4
’-Chloroacetophenone
1
H NMR: d = 2.59 (s, 3H), 7.42-7.46 (m, 2H), 7.90 (dt, J = 2.1, 8.9
Hz, 2H).
(
9) Mino, T.; Masuda, S.; Nishio, M.; Yamashita, M. J. Org.
Chem. 1997, 62, 2633.
+
GC-MS: m/z (%) = 154 (M , 25), 139 (100), 111 (59), 75 (40).
(
10) Fieser, L. F. J. Am. Chem. Soc. 1954, 76, 1945.
(11) H NMR: d = 1.84 (s, 3H), 2.18-2.28 (m, 2H), 2.81-2.91 (m,
1
4
’-Nitroacetophenone
1
H NMR: d = 2.69 (s, 3H), 8.10-8.14 (m, 2H), 8.32 (dt, J = 2.1, 8.9
Hz, 2H).
2H), 3.30-3.43 (m, 4H), 7.15-7.32 (m, 5H); GC-MS: m/z (%)
+
= 224 (M , 10), 119 (100), 91 (57).
+
(12) Dictionary of Organic Compounds, 6th ed.; Chapman and
GC-MS: m/z (%) = 165 (M , 17), 150 (100), 104 (36), 92 (22).
Hall: London, 1996.
3
,3,5-Trimethylcyclohexanone
H NMR: d = 0.88 (s, 3H), 1.01-1.06 (m, 6H), 1.27-1.33 (m, 1H),
.57-1.61 (m, 1H), 1.86-1.93 (m, 1H), 1.98-2.08 (m, 2H), 2.15-2.34
1
1
Article Identifier:
(
m, 2H).
1
437-210X,E;1999,0,12,2024,2026,ftx,en;F04099SS.pdf
Synthesis 1999, No. 12, 2024–2026 ISSN 0039-7881 © Thieme Stuttgart · New York