Al(OTf)3 as an efficient catalyst for one-pot synthesis of primary diethyl 1-aminophosphonates under solvent-free conditions

Article abstract of DOI:10.1080/00397910802369695

A simple and general method has been developed for the one-pot, three-component synthesis of a variety of primary 1-aminophosphonates catalyzed by Al(OTf)3 under solvent-free conditions in good to high yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802369695

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Al(OTf)3 as an Efficient
Catalyst for One-Pot Synthesis
of Primary Diethyl 1-
Aminophosphonates Under
Solvent-Free Conditions
Sara Sobhani a & Zahra Tashrifi a
a Department of Chemistry , College of Sciences,
Birjand University , Birjand, Iran
Published online: 15 Feb 2011.
To cite this article: Sara Sobhani & Zahra Tashrifi (2008) Al(OTf)3 as an Efficient
Catalyst for One-Pot Synthesis of Primary Diethyl 1-Aminophosphonates Under
Solvent-Free Conditions, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:1, 120-131, DOI:
10.1080/00397910802369695
To link to this article: http://dx.doi.org/10.1080/00397910802369695
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Synthetic Communications1, 39: 120–131, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802369695
Al(OTf)3 as an Efficient Catalyst for
One-Pot Synthesis of Primary Diethyl
1-Aminophosphonates Under
Solvent-Free Conditions
Sara Sobhani and Zahra Tashrifi
Department of Chemistry, College of Sciences,
Birjand University, Birjand, Iran
Abstract: A simple and general method has been developed for the one-pot,
three-component synthesis of a variety of primary 1-aminophosphonates
catalyzed by Al(OTf)3 under solvent-free conditions in good to high yields.
Keywords: Aldehydes, aluminium triflate, diethyl phosphite, ketones, primary
1-aminophosphonates, solvent-free
INTRODUCTION
Aminophosphonic acids have been attracting a good deal of attention
ever since the first compounds with a phosphorus–carbon bond were
detected among natural products.[1] As mimetics of the natural amino
acids, they seem to be strong potential bioregulators. These compounds
are found to be the substrates and inhibitors of enzymes,[2–4] as well as
plant-growth regulators,[5] herbicides,[6] and carriers of hydrophilic
organic molecules across phospholipid membranes.[7] They also display
antibacterial and neuronal activities.[8,9] Therefore, the synthesis of
1-aminophosphonates (Scheme 1) as naturally occuring 1-aminoacids
Received June 12, 2008.
Address correspondence to Sara Sobhani, Department of Chemistry, College
of Sciences, Birjand University, Birjand 414, Iran. E-mail: sobhanisara@yahoo.
com, ssobhani@birjand.ac.ir
120

Primary Aminophosphonate Synthesis
121
Scheme 1. Primary 1-aminophosphonates: R3¼H, R4¼H; secondary 1-amino-
phosphonates: R3¼alkyl, aryl; R4¼H; and tertiary 1-aminophosphonates:
R3¼alkyl, aryl; R4¼alkyl, aryl.
has attracted a significant interest by organic chemists in recent years. In
this area, many elegant new methods and reagents for the one-pot synth-
esis of secondary and tertiary 1-aminophosphonates have been
reported.[10–15] However, few attempts have been made for the one-pot
synthesis of primary 1-aminophosphonates. The most typical procedure
for the one-pot synthesis of primary 1-aminophosphonates is a
Strecker-type reaction,[16,17] which involves the treatment of an aldehyde
with ammonia and diethyl phosphite. This method, however, is not high
yielding and is unsuitable for large-scaleꢀproduction because the reaction
is performed on a sealed vessel at 100 C. Recently, in these reactions,
volatile ammonia has been substituted by nonvolatile ammonium salts.
Therefore, the reaction is not necessirily carried out in a sealed vessel.
These reactions conducted by catalysts such as molecular sieve,[17] tetra-
tert-butyl-substituted phthalocyanine,[18] and solid supports.[19–22] However,
these procedures suffer from at least one of the following drawbacks: long
reaction times,[17,18] need for a promoter such as microwaves,[19–22] ammen-
able only for aldehydes as carbonyl compounds,[17,19–22] low yields of the
products,[17,18] or use of large amounts of solid supports or catayst, which
would eventually result in the generation of a large amount of toxic
waste.[19–22] Therefore, it is necessary to further develop an efficient and
convenient method for one-pot synthesis of such a significant scaffold.
RESULTS AND DISCUSSION
As part of our efforts to introduce new methods for the synthesis of phos-
phonate derivatives,[23–27] we have recently reported different metal
triflates [M(OTf)x; M ¼ Al, Mg, Ce, Li, Cu] as efficient catalysts for the
successful one-pot synthesis of secondary diethyl 1-aminophosphonates
under solvent-free conditions.[27] We envisioned that these kinds
of the catalysts could be effective for the one-pot synthesis of primary
1-aminophosphonates under solvent-free conditions.

122
S. Sobhani and Z. Tashrifi
Table 1. One-pot synthesis of primary diethyl 1-aminophosphonate (2a) in the
presence of different metal triflates at 100 ꢀC under solvent-free conditions
Entry
M(OTf)x
Time (min)
Yielda (%)
1
2
3
4
5
Al(OTf)3
Ce(OTf)4
Cu(OTf)2
LiOTf
5
94
81
53
55
72
30
60
30
15
Mg(OTf)2
aIsolated yield.
First, we examined the feasibility of the reaction of benzaldehyde,
ammonium carbonate, and diethyl phosphite as a model in the presence
of different metal triflates [M(OTf)x; M ¼ Al, Mg, Ce, Li, Cu] under
solvent-free conditions (Table 1, Scheme 2). Among the metal triflates
tested, Al(OTf)3 turned out to be the most effective catalyst leading
to N-(phenylmethylene)-1-aminophenylmethylphosphonate (1a) in 97%
1
yield (Scheme 2). The H NMR spectrum of (1a) exhibited a doublet
at 8.40 ppm, which is indicative for coupling of HC-P (JHP ¼ 5 Hz)
moiety in the molecule. Hydrolysis of 1a with HCl and neutralization
of the chloride salt gave 1-aminophenylmethylphosphonate (2a)
(Scheme 2).
A screening of several ammonium salts [(NH4)nX; X ¼ OAc, NO3,
CO3, Cl, Br] performed a similar reaction catalyzed by Al(OTf)3.
Ammonium acetate and ammonium carbonate were found to be the most
effective ammonia sources that gave the desired product (1a). Formation
of 1a could not be detected in the case of ammonium nitrate, ammonium
chloride, and ammonium bromide.
To show the generality and scope of this synthetic method, the
reaction of various structurally diverse aldehydes and ketones were
Scheme 2. One-pot synthesis of diethyl 1-amino phenylmethylphosphonate (2a).

Primary Aminophosphonate Synthesis
123
Scheme 3. One-pot synthesis of different types of primary diethyl
1-aminophosphonates.
examined in the presence of Al(OTf)3 (Scheme 3).The results are
summarized in Table 2.
As shown in Table 2, different substituted benzaldehydes were success-
fully converted to the corresponding primary 1-aminophosphontes (2a–j)
in high yields under solvent-free conditions by reaction with ammonium
carbonate or ammonium acetate. Moreover, heteroaromatic, polynuclear,
and aliphatic aldehydes were all effective substrates to successfully execute
the solvent-free reactions by Al(OTf)3 (entries 12–16). Bis-functional
1-aminophosphonates (2k) were also prepared successfully by the pre-
sented method in high yields from terephthaldehyde (Table 2, entry 11).
In addition to aldehydes, some ketones were also screened to carry out
the coupling reaction by Al(OTf)3 under solvent-free conditions. For cyclic
ketones, the expected compounds could be achieved in 65–85% yields.
However, no product was gained when aromatic ketones such as
acetophenone and 1-indanone were involved in such coupling reactions.
It should be noted that no competitive side reactions such as the formation
of 1-hydroxyphosphonates were observed in these transformations.
In conclusion, in this study we have successfully extended the use
of Al(OTf)3 as an efficient catalyst for the one-pot, three-component
synthesis of primary 1-aminophosphontes from aldehydes=ketones,
ammonium acetate=carbonate, and diethyl phosphite in good to high
yields under solvent-free conditions. Short reaction time, applicability
for various types of aldehydes and also cyclic ketones, use of diethyl
phosphite instead of smelly triethyl phosphite, and use of a catalytic
amount of Al(OTf)3 are the highlights of this protocol. All these make
the present protocol a suitable procedure for the synthesis of different
types of 1-aminophosphontes.
EXPERIMENTAL
Chemicals were purchased from Merck and Fluka chemical companies.
All of the products were identified by their physical and spectral data.

124

125

126

127

128

Primary Aminophosphonate Synthesis
129
IR spectra were run on a Perkin-Elmer 780 instrument. NMR spectra
were recorded on a Bruker Avance DPX-250. Mass spectra were
recorded on a Shimadzu GCMS-QP5050A. The purity of the products
and the progress of the reactions were accomplished by thin-layer chro-
matography (TLC) on silica-gel polygram SILG=UV254 plates.
General Procedure for the Preparation of Primary Diethyl
1-Aminophosphonates (2a–t)
Al(OTf)3 (0.01 mmol) was added to a stirring mixture of aldehyde=
ketone (2 mmol), (NH4)2CO3(1 mmol)=NH4OAc (2 mmol), and diethyl
phosphite (2 mmol). The resulting mixture was heated in an oil bath
ꢀ
at 100 C and stirred for an appropriate time (Table 2). The reaction
mixture was cooled and acidified to pH 1 by HCl (aq). The solution
was washed with Et2O (2 ꢁ 10 mL). The aqueous phase was then made
alkaline with NaOH (aq), and the product was extracted with Et2O
(2 ꢁ 10 mL). The combined organic phase was dried over Na2SO4 and
concentrated under reduced pressure. In most cases, evaporation of
the filtrate yielded the pure product. If more purification was required,
the crude product was purified by chromatography on silca gel eluted
with n-hexane–EtOAc (1:3).
Spectral Data for Diethyl 1-Aminophenylmethylphosphonate (2a)
1
Pale yellow oil. IR: 3385, 3298 (NH2) cmꢂ1; H NMR (CDCl3, TMS): d
2
2
1.16 (t, 3 H, JH,H ¼ 7.0 Hz, OCH2CH3), 1.26 (t, 3 H, JH,H ¼ 7.0 Hz,
OCH2CH3), 2.37 (bs, NH2), 3.82–4.09 (m, 4 H, OCH2CH3), 4.24 (d, 1
H, JP,H ¼ 17.2 Hz, CH), 7.21–7.46 (m, 5 H, C6H5) ppm. 13C NMR
2
3
(CDCl3, TMS):
d
16.3 (d, JC,P ¼ 5.7 Hz, OCH2CH3), 16.4 (d,
3JC,P ¼ 5.7 Hz, OCH2CH3), 54.0 (d, JC,P ¼ 149.5 Hz, CH), 62.7 (d,
1
2JC,P ¼ 7.7 Hz, OCH2CH3), 62.8 (d, JC,P ¼ 7.7 Hz, OCH2CH3), 127.5,
2
127.8, 128.2, 128.5 (C6H5) ppm. MS (70 eV), m=z (%): 243 (Mþ, 1), 106
[M-P(O)(OEt)2, 100].
ACKNOWLEDGMENTS
We are thankful to Birjand University Research Council for the support
of this work.

130
S. Sobhani and Z. Tashrifi
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