Oxidative deamination of α-aminophosphonates and amines by zinc dichromate trihydrate (ZnCr2O73H2O) under solvent-free conditions at room temperature

Article abstract of DOI:10.1055/s-0029-1219174

A novel method for the rapid and efficient conversion of a variety of -aminophosphonates to α-ketophosphonates using ZnCr₂O ₇3H₂O via oxidative deamination under solvent-free conditions at room temperature is described. This method is also applicable to the rapid and highly selective oxidation of various types of ordinary amines (primary and secondary) to aldehydes and ketones in good to high yields. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1219174

LETTER
383
Oxidative Deamination of a-Aminophosphonates and Amines by Zinc
Dichromate Trihydrate (ZnCr2O7·3H2O) under Solvent-Free Conditions
at Room Temperature
O
xidative De
a
a
mination of
r
a
-Amin
a
ophosphonates an
S
d Amines obhani,* Mahdi Faal Maleki
Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
Fax +98(561)2502009; E-mail: ssobhani@birjand.ac.ir; E-mail: sobhanisara@yahoo.com
Received 25 August 2009
have recently been receiving much interest in organic syn-
thesis.10h,13 Solvent-free reactions are carried out by stir-
ring or simple grinding of the reaction mixture in a mortar
with a pestle.10i,14
Abstract: A novel method for the rapid and efficient conversion of
a variety of a-aminophosphonates to a-ketophosphonates using
ZnCr2O7·3H2O via oxidative deamination under solvent-free condi-
tions at room temperature is described. This method is also applica-
ble to the rapid and highly selective oxidation of various types of
ordinary amines (primary and secondary) to aldehydes and ketones
in good to high yields.
In recent years, we have focused our attention on the de-
velopment of methods for the synthesis of phosphonate
derivatives.10f–i,11b,c,15 In this context we have observed
that zinc dichromate trihydrate (ZnCr2O7·3H2O) may be
used as an efficient oxidizing reagent for the synthesis of
a-ketophosphonates from a-hydroxyphosphonates under
solvent-free conditions.10i These observations prompted
us to examine the efficiency of ZnCr2O7·3H2O for the ox-
idation of primary a-aminophosphonates to a-ketophos-
phonates.
Key words: oxidative deamination, a-ketophosphonates, a-hy-
droxyphosphonates, amines, aldehydes
a-Ketophosphonates are an important subdivision of or-
ganophosphorus compounds. The adjacent carbonyl and
phosphoryl functional groups make a-ketophosphonates
interesting compounds as potential precursors in organic
synthesis.1 For instance, it is possible to derive hydra-
zones,2 imines,3 a,a-difluorophosphonates4 and oximes5
from the carbonyl function; to reduce a-ketophosphonates
to the corresponding a-hydroxyphosphonates,6 or use
them in Wittig, Baeyer–Villiger, or Schmidt reactions.1a,7
The C(O)–P bonds in these compounds are known to be
sensitive towards hydrolysis and acidic conditions.8
Therefore, handling of a-ketophosphonates is not trivial
and requires special precautions.8 The Michael–Arbuzov
reaction is a general method for the preparation of a-keto-
phosphonates from acyl chlorides and trialkylphosphites.9
This is a useful method; however, it is restricted insofar as
only commercially or synthetically available acid chlo-
rides can be used. Oxidation methods are alternative pro-
cedures for the preparation of a-ketophosphonates. These
methods are limited to the oxidation of a-hydroxyphos-
phonates.4,10 a-Aminophosphonates, which are easily pre-
pared from commercially available materials,11 are also
useful precursors for the preparation of a-ketophospho-
nates. A literature survey indicates that, in contrast to the
existing methods for the oxidation of a-hydroxyphospho-
nates, few methods are known for the efficient oxidation
of a-aminophosphonates. Potassium permanganate has
been reported for the oxidation of a-aminophosphonates,
but in this case, a-nitrophosphonates were produced as the
sole products.12
At first we examined the feasibility of the oxidation reac-
tion of a-amino(phenyl)methylphosphonate (1a) as a
model in the presence of ZnCr2O7·3H2O under solvent-
free conditions at room temperature. The results showed
that 1a underwent a fast oxidative deamination and pro-
duced a-benzoylphosphonate (2a) as the sole product in
95% yield. We next investigated the applicability of this
method for the oxidation of various types of a-amino-
phosphonates to a-ketophosphonates (Scheme 1). The
results of these studies are summarized in Table 1.
As depicted in Table 1, this method worked well for the
oxidative deamination of a-amino-(phenyl)methylphos-
phonates bearing both electron-releasing and electron-
withdrawing groups on the phenyl group (1b–f) and pro-
duced the corresponding a-ketophosphonates (2b–f) in
85–98% yields. The oxidation of a-amino-2-naphthyl-
and 2-thienylphosphonate (1g and 1h) as examples of
polyaromatic and heteroaryl phosphonate derivatives pro-
ceeded well to afford the desired products 2g and 2h in
98% and 85% yields, respectively. a-Aminoalkylphos-
phonates 1i and 1j were also oxidized selectively to the
corresponding a-ketophosphonates under these reaction
conditions.
O
P
O
P
ZnCr2O7⋅3H2O
R
R
OEt
OEt
OEt
OEt
In view of environmental and economical demands, sim-
plicity in processes and low costs, solvent-free reactions
solvent-free, r.t., 5–15 min
NH2
1a–j
O
2a–j
85–98%
R = aryl, heteroaryl, alkyl
SYNLETT 2010, No. 3, pp 0383–0386
Advanced online publication: 08.01.2010
1
2.
0
1.
2
0
1
0
Scheme 1
DOI: 10.1055/s-0029-1219174; Art ID: D23209ST
© Georg Thieme Verlag Stuttgart · New York

384
S. Sobhani, M. F. Maleki
LETTER
Table 1 Oxidation of a-Aminophosphonates to a-Ketophospho-
nates by ZnCr2O7·3H2O under Solvent-Free Conditions at Room
Temperature
Table 2 Oxidative Deamination of Amines in the Presence of
ZnCr2O7·3H2O under Solvent-Free Conditions at Room Temperature
Entry Amine
Product
Yield
(%)a
Product 2
R
Time (min)
Yield (%)a
CHO
CHO
CHO
2a
2b
2c
2d
2e
2f
Ph
5
95
90
98
95
95
85
98
85
85
85
NH2
NH2
NH2
1
98b
3-ClC6H4
4-BrC6H4
4-ClC6H4
4-MeOC6H4
4-MeC6H4
2-naphthyl
2-thienyl
n-hexyl
i-Pr
5
Cl
Cl
5
2
90
5
10
10
15
10
5
OMe
OMe
3
92
2g
2h
2i
NH2
O
4
5
6
97
97
90
NH2
O
2j
10
a Yields refer to those of pure isolated products characterized by com-
parison of their spectroscopic data with those of authentic sam-
ples.10,16 Conditions: ZnCr2O7·3H2O (1 equiv).
Ph
O
Ph
NH2
NH2
O
7
98
Workup of the reaction mixture was easy and, by a simple
vacuum distillation, pure products were isolated. Further-
more, cleavage of the C(O)–P bond was not observed in
any of these reactions and a-ketophosphonates were the
only products obtained from these reactions.
H2N
8
9
91c
92
OHC
CHO
NH2
The oxidation of amines as a significant class of available
building blocks and fundamental synthetic intermediates
has received much attention from organic chemists. Oxi-
dation of amines can lead to functional groups including
imines, amides, nitro, oximes, nitriles, aldehydes, and ke-
tones.17 Within these transformations, selective conver-
sion of amines to carbonyl compounds is a relatively
common biological process and has received much atten-
tion from organic chemists in recent years.17e–17j
NH
CHO
10
11
90
94
OHC
OHC
CHO
N
H
CHO
In order to obtain a fuller understanding of the reactivity
profile of this reagent, we investigated the oxidation of a
variety of ordinary amines utilizing ZnCr2O7·3H2O under
the same reaction conditions. The results of these studies
are listed in Table 2.
N
H
PhCHO
90
92
H
N
12
13
Ph
Ph
Ph
CHO
CHO
OMe
90d
95c
As shown in Table 2, substituted benzylamines with
electron-donating and electron-withdrawing groups were
selectively oxidized to their corresponding aldehydes in
high yields (entries 1–3). Aliphatic amines were also
cleanly converted to the corresponding aldehydes and ke-
tones in excellent yields (entries 4–7). The procedure was
also suitable for the oxidation of 1,4-bis(aminometh-
yl)benzene as an example of a difunctional amine and pro-
duced terephthaldehyde in high yield (entry 8). In addition
to primary amines, some secondary amines were also
screened to examine their oxidation by ZnCr2O7·3H2O un-
der the above reaction conditions. The results showed that
the oxidation reaction of dialkylamines and benzyl alkyl-
amines worked well, and the expected products were ob-
tained in 90–94% yields (entries 9–12). Oxidation of
Ph
N
H
O
OMe
O
O
(EtO)2P
Ph
(EtO)2P
Ph
14
N
H
a Yields refer to those of pure isolated products characterized by com-
parison of their spectroscopic data with those of authentic samples.
Reaction occurred instantaneously. Conditions: ZnCr2O7·3H2O (1
equiv, except for entries 1, 8, 13, and 14).
b Conditions: ZnCr2O7·3H2O (0.5 equiv).
c Conditions: ZnCr2O7·3H2O (4 equiv).
d Conditions: ZnCr2O7·3H2O (2 equiv).
Synlett 2010, No. 3, 383–386 © Thieme Stuttgart · New York

LETTER
Oxidative Deamination of a-Aminophosphonates and Amines
385
4-BrC6H4CH2NHPMP
PhCHO + 4-BrC6H4CHO
97%
0%
PhCH2CH2OH
PhCHO + PhCH2CHO
80% 15%
PhCH(OH)Me
PhCHO + PhC(O)Me
82% 12%
PhCH2CH2OTMS
PhCH(OTMS)Me
PhCH2CH2OTHP
PhCH(OTHP)Me
PhCHO + PhCH2CHO
85% 10%
PhCHO + PhC(O)Me
94% trace
ZnCr2O7⋅3 H2O
PhCH2NH2
PhCHO + PhCH2CHO
91% 5%
solvent-free, r.t., 10 min
PhCHO + PhC(O)Me
92% 5%
O
Ph
O
PhCHO + PhC(O)Me
85% 9%
S
Ph
S
PhCHO + PhC(O)Me
84% 10%
NOH
Ph
Ph
PhCHO + PhC(O)Me
81%
16%
O
S
S
PhCHO +
90%
7%
O
S
PhCHO + PhS
91% 8%
Scheme 2
amines protected with a p-methoxyphenyl group pro- formation, simple workup, and excellent selectivity for
duced the corresponding carbonyl compounds in high the formation of carbonyl compounds make this method
yields (entries 13 and 14). The protecting group was re- an attractive and useful contribution to the present meth-
leased as benzoquinone in these reactions. No byproduct odologies.
was formed in any of these transformations, and the
amines were cleanly and selectively oxidized to aldehydes
and ketones.
General Procedure for the Preparation of a-Ketophosphonates
2a–j by the Oxidation of a-Aminophosphonates 1a–j
To determine the selectivity of this method further, the ox-
idation of benzylamine in the presence of different func-
tional groups was studied (Scheme 2). As indicated in
Scheme 2, the reactions proceeded with high chemoselec-
tivity in favor of amine oxidation, and benzylamine was
transformed to benzaldehyde in good to high yields.
A mixture of a-aminophosphonate (1, 5 mmol) and ZnCr2O7·3H2O
(5 mmol) was ground together in a mortar with pestle for 5–15 min.
Then the reaction mixture was washed with Et2O (4 × 15 mL), dried
over anhyd Na2SO4, and filtered. The solvent was evaporated under
reduced pressure to give the crude product. The pure product 2 was
obtained by vacuum distillation in 85–98% yields (Table 1).
It is noteworthy that ZnCr2O7⋅3H2O has been used as an
efficient reagent for the fast oxidation of alcohols, sul-
fides, ethers, acetals, dithioacetals, oximes, silyl, and
pyranyl ethers in recent years.18
General Procedure for the Oxidation of Amines to Aldehydes
and Ketones
A mixture of amine (1 mmol) and ZnCr2O7·3H2O (0.5–4 mmol,
Table 2) was ground together in a mortar with a pestle. The reaction
occurred immediately, and the mixture was washed with Et2O
(2 × 15 mL), dried over anhyd Na2SO4, and filtered. In most cases
evaporation of the filtrate yielded the desired pure product. If fur-
ther purification was required, the crude product was purified by
column chromatography on silica gel.
In conclusion, we have found that ZnCr2O7·3H2O can be
used as a new and efficient reagent for the facile prepara-
tion of a variety of a-ketophosphonates from a-amino-
phosphonates as viable substrates. This method is also
applicable to the oxidative deamination of various types
of primary and secondary amines under solvent-free con-
ditions at room temperature. Short reaction times, high
chemoselectivity, good to high yields, lack of byproduct
Aknowledgment
We are thankful to Birjand University Research Council for their
support of this work.
Synlett 2010, No. 3, 383–386 © Thieme Stuttgart · New York

386
S. Sobhani, M. F. Maleki
LETTER
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