One-pot synthesis of primary 1-aminophosphonates: Coupling reaction of carbonyl compounds, hexamethyldisilazane, and diethyl phosphite catalyzed by al(otf)3

Article abstract of DOI:10.1002/hc.20517

Al(OTf)3 has been utilized as a new and efficient catalyst for the selective synthesis of primary 1-aminophosphonates by a one-pot coupling reaction of various types of aldehydes/ketones, hexamethyldisilazane, and diethyl phosphite under solvent-free cond

Full text of DOI:10.1002/hc.20517

Heteroatom Chemistry
Volume 20, Number 2, 2009
One-Pot Synthesis of Primary
1-Aminophosphonates: Coupling Reaction of
Carbonyl Compounds, Hexamethyldisilazane,
and Diethyl Phosphite Catalyzed by Al(OTf)
3
Sara Sobhani and Zahra Tashrifi
Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
Received 14 July 2008; revised 2 December 2008, 4 February 2009
(b) Hofmann rearrangement of substituted phospho-
noacetic esters [11]; (c) alkylation of nucleophilic
precursors such as Schiff bases [12]; (d) conver-
sion of the corresponding 1-hydroxyphosphonates
to 1-aminophosphonates [13,14]; (e) reduction of
1-hydroxyiminophosphonates [15,16]; and (f) addi-
tion of the P H function to nitriles [17]. In contrast
to the widespread studies on the one-pot synthe-
sis of secondary and tertiary 1-aminophosphonates
[18–23], relatively few papers have reported on the
one-pot synthesis of primary 1-aminophosphonates.
The most typical procedure for the one-pot synthe-
sis of primary 1-aminophosphonates is a Strecker-
type reaction [24,25], which involves the treatment
of an aldehyde with ammonia and diethyl phos-
phite. This method, however, is not high yielding
and is unsuitable for large-scale production since
the reaction is performed in a sealed vessel at 100◦C.
Recently, in this reaction, ammonia has been substi-
tuted by ammonium salts or hexamethyldisilazane
(HMDS). These reactions are conducted by catalysts
such as molecular sieves [25], LiClO4 [26], tetra-
tert-butyl-substituted phthalocyanine [27], and solid
supports [28–32]. However, all the existing methods
have displayed drawbacks, such as having long reac-
tion times [25,27], being amenable only for aldehy-
des as carbonyl compounds [25,28–33], using foul-
smelling trialkyl phosphite as the phosphorus nucle-
ophile [26], requiring a promoter such as microwave
treatment [28–31], giving low yields of the prod-
ucts [25,27], producing 1-hydroxyphosphonates or
ABSTRACT: Al(OTf)3 has been utilized as a new and
efficient catalyst for the selective synthesis of primary
1-aminophosphonates by a one-pot coupling reaction
of various types of aldehydes/ketones, hexamethyldis-
ilazane, and diethyl phosphite under solvent-free con-
ditions. 2009 Wiley Periodicals, Inc. Heteroatom Chem
20:109–115, 2009; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20517
ꢀ
C
INTRODUCTION
1-Aminophosphonates (Scheme 1), which are con-
sidered as phosphorus analogues of 1-amino acids,
have received considerable attention owing to their
biological and biochemical properties. They have
been used as antibacterial agents [1], carriers of
hydrophilic organic molecules across phospholipid
membranes [2], enzyme inhibitors [3–5] (includ-
ing human immunodeficiency virus protease) [6,7],
as well as plant growth regulators [8]. The wide
application of 1-aminophosphonates has provoked
the search for simple and efficient procedures for
the synthesis of such significant scaffolds in recent
years. Several multistep approaches to the synthe-
sis of primary 1-aminophosphonates are available:
(a) addition of the P H function to imines [9,10];
Correspondence to: Sara Sobhani; e-mail: sobhanisara@yahoo.
com, ssobhani@birjand.ac.ir.
c
ꢀ
2009 Wiley Periodicals, Inc.
109

110 Sobhani and Tashrifi
R2
O
TABLE 1 One-Pot Synthesis of Primary 1-Aminophenyl-
methylphosphonate (2) in the Presence of M(OTf)x at 80◦C
Under Solvent-Free Conditions
R1
P(OR5)2
NR3R4
Entry
M(OTf)x
Time (h)
Yielda,b (%)
Primary 1−aminophosphonates: R3 = H; R4 = H
Secondary 1−aminophosphonates: R3 = alkyl, aryl; R4 = H
Tertiary1−aminophosphonates: R3 = alkyl, aryl; R4 = alkyl, aryl
1
2
3
4
5
6
Al(OTf)3
Ce(OTf)4
Cu(OTf)2
LiOTf
Mg(OTf)2
Zn(OTf)2
0.5
3
2
5
2
96
72
83
80
65
52c
SCHEME 1
3
aIsolated yield based on half of aldehyde.
bConditions: benzaldehyde (2 mmol), HMDS (1.2 mmol), and diethyl
phosphite (1.2 mmol).
1-trimethylsilyloxyphosphonates as side products
[33], and using large amounts of solid supports or
catalysts that would eventually result in the genera-
tion of a large amount of toxic waste [26,28–31].
cDiethyl 1-(trimethylsilyloxy)-1-phenylmethylphosphonate was ob-
tained in 43% yield as a side product.
hibits a doublet at 8.40 ppm, which is indicative of
the coupling for the HC P (JHP = 5 Hz) moiety in
the imine (1) in 98% yield (based on 1H NMR
data) [(The structure of 1 was confirmed by
spectral data of pure imine, isolated from the
reaction mixture by plate chromatography and
RESULTS AND DISCUSSIONS
As part of our efforts to introduce new methods for
the synthesis of phosphonate derivatives [34–38], we
have recently reported on different metal triflates
[M(OTf)x; M = Al, Mg, Ce, Li, Cu] as efficient cat-
alysts for the successful one-pot synthesis of sec-
ondary diethyl 1-aminophosphonates under solvent-
free conditions [38]. Thus, we envisioned that these
types of catalysts could be effective for the one-pot
synthesis of primary 1-aminophosphonates under
solvent-free conditions.
eluted with n-hexane:ethyl acetate (1:3;
R
=
f
0.65)]. Hydrolysis of 1 with HCl and neutral-
ization of the resulting chloride salt gave 1-
aminophenylmethylphosphonate (2) (Scheme 2)
[R = 0.25 [n-hexane:ethyl acetate (1:3)]. Excellent
f
selectivity for the synthesis of 1 was observed
in the presence of Al(OTf)3, Mg(OTf)2, Ce(OTf)4,
LiOTf, and Cu(OTf)2 with no formation of diethyl 1-
(trimethylsilyloxy)-1-phenylmethylphosphonate and
diethyl 1-hydroxyphenylmethylphosphonate. In the
presence of Zn(OTf)2, lower selectivity for 2 was
observed owing to the formation of diethyl 1-
(trimethylsilyloxy)-1-phenylmethylphosphonate in
43% yield as a side product (Table 1, Entry 6).
First, we examined the feasibility of the re-
action between benzaldehyde, HMDS, and di-
ethyl phosphite as a model in the presence of
different metal triflates [M(OTf)x; M = Al, Mg,
Ce, Li, Cu, Zn] under solvent-free conditions
(Table 1, Scheme 2). Among the metal triflates
tested, Al(OTf)3 turned out to be the most ef-
fective catalyst leading to N-(phenylmethylene)-1-
aminophenylmethylphosphonate (1) (Scheme 2).
To establish the generality of this method,
various aldehydes and ketones were subjected to
1
The H NMR spectrum of the reaction mixture ex-
O
O
H
O
HCl (aq)
M(OTf)x (10 mol%)
H
C
(Me3Si)2NH
HP(OEt)2
PhCHO +
Ph
P(OEt)2
Ph
P(OEt)2
NH3Cl
Solvent free, 80°C
N
CH
Ph
NaOH (aq)
1
H
O
Ph
P(OEt)2
NH2
2
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

One-Pot Synthesis of Primary 1-Aminophosphonates 111
R2
O
R1
R2
O
Al(OTf)3 (10 mol%)
R1
P(OEt)2
(Me3Si)2NH
HP(OEt)2
O
Solvent free, 80°C
NH2
70% – 99%
R1 = aryl, alkyl, heteroaryl
R2 = H, alkyl
SCHEME 3
one-pot reaction with HMDS and diethyl phosphite
catalyzed by Al(OTf)3 under solvent-free conditions
(Scheme 3). The results are listed in Table 2.
foul-smelling triethyl phosphite, high yields, the sup-
pression of side products and tar formation, the sim-
ple extractive workup, and the nonrequirement of
additional promoters other than a catalytic amount
of Al(OTf)3 make this method an attractive and use-
ful contribution to the present methodologies.
As is indicated in Table 2, benzaldehydes
substituted with different electron-donating and
electron-withdrawing groups underwent smooth
reactions with HMDS and diethyl phosphite
(Entries 1–8) and the desired products were ob-
tained in good to high yields. The catalyst was
compatible with functional groups on the aromatic
ring, such as Cl and O Me groups. No competitive
nucleophilic methyl ether cleavage was observed for
the substrate having an aryl O Me group (Table 2,
Entry 4) in spite of the good nucleophilic property of
phosphites. Naphthalene-2-carbaldehyde, a polynu-
clear aromatic aldehyde, also reacted with diethyl
phosphite to give the desired product (10) in high
yield. This procedure worked well for the synthesis
of primary diethyl α-aminophosphonates 11–13
from acid-sensitive aldehydes such as thiophene-2-
carbaldehyde, furan-2-carbaldehyde, and indol-3-
carbaldehyde without any decomposition or poly-
merization. The present method is also suitable for
the preparation of primary 1-aminophosphonates
from aliphatic aldehydes (Table 2, Entries 13 and
14). In addition to aldehydes, some ketones were
also screened to examine the direct coupling by
Al(OTf)3 under these reaction conditions. The re-
sults showed that the reactions involving alkyl aryl
ketones, acyclic dialkyl ketones, and cyclic ketones
worked well and the expected products could be
obtained smoothly in 70% to 96% yields (Table 2,
Entries 15–23). (In the case of ketones, no imine
was formed, according to the spectral data of the
isolated product by plate chromatography before
acidic workup.) However, no product was obtained
when diaryl ketones such as benzophenone or 9H-
fluoren-9-one (Table 2, Entries 24 and 25) were used
in this one-pot reaction under the same conditions.
In conclusion, we have introduced Al(OTf)3 as a
new and efficient catalyst for the selective synthesis
of primary 1-aminophosphonates by the one-pot re-
action of various types of aldehydes/ketones, HMDS,
and diethyl phosphite. The applicability of diethyl
phosphite as a phosphorus nucleophile instead of the
EXPERIMENTAL
General
Chemicals were purchased from the Merck and
Fluka chemical companies. All of the products were
identified by their physical and spectral data. IR
spectra were measured on a Perkin Elmer 780
spectrophotometer. NMR spectra were recorded
on a Bruker Avance DPX-250 NMR spectrometer.
Mass spectra were recorded on a Shimadzu GCMS-
QP5050A gas chromatograph mass spectrometer.
The purity of the products and the progress of the re-
actions were determined by thin layer chromatogra-
phy (TLC) on silica-gel polygram SILG/UV254 plates
or by gas chromatography (GC) on a Shimadzu
model GC-14A gas chromatograph.
General Procedure for the Preparation of
Primary Diethyl 1-Aminophosphonates
A mixture of an aldehyde/ketone (1.5 mmol),
HMDS (1.2 mmol), diethyl phosphite (1.2 mmol),
and Al(OTf)3 (0.01 mmol) was stirred in an oil
bath at 80◦C for an appropriate amount of time
(Table 2). Progress of the reaction was moni-
tored with TLC or GC [In the case of aldehy-
des, the progress of the reaction was also mon-
itored by 1H NMR measurements (conversion =
90%–100%)]. The reaction mixture was cooled and
acidified to pH 1 by HCl (aq). The solution was
washed with EtOAc (2 × 10 mL). The aqueous phase
was then made alkaline with NaOH (aq) and the
product was extracted with EtOAc (2 × 10 mL). The
combined organic phase was dried over Na2SO4 and
concentrated under reduced pressure to give diethyl
1-aminophosphonates as pale yellow oils with high
purity [R = 0.2–0.35 [n-hexane:ethyl acetate (1:3)].
f
Heteroatom Chemistry DOI 10.1002/hc

112 Sobhani and Tashrifi
TABLE 2 One-Pot Synthesis of Primary 1-Aminophosphonates from Aldehydes/Ketones, HMDS and Diethyl Phosphite in the
Presence of Al(OTf)3 at 80◦C under Solvent-Free Conditions
Entry
1
R1
R2
H
Product
Time
Yielda,b (%)
96c
2
30 min
2
H
3
25 min
94
Me
3
4
5
H
H
H
4
5
6
2 h
86c
92
Me
30 min
15 min
MeO
99
Cl
6
H
7
30 min
91
Cl
Cl
7
8
9
H
H
H
8
9
1.5 h
20 min
45 min
93c
83c
90
Br
10
10
11
H
H
11
12
30 min
1 h
92
98
S
O
12
H
13
2 h
92
N
H
13
14
H
H
14
15
40 min
35 min
88
93
5
15
16
Me
Me
16
17
45 min
2 h
83d
70d
N
17
18
19
iso-Butyl
Et
Et
Me
MeO2C
18
19
20
30 min
35 min
15 min
96d
92d
95d
Me
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

One-Pot Synthesis of Primary 1-Aminophosphonates 113
TABLE 2 Continued
Entry
20
R1
R2
Product
Time
Yielda,b (%)
87d
21
30 min
21
22
23
22
23
24
2 h
45 min
1 h
84d
85d
83d
24
25
25
26
24 h
24 h
0
0
aIsolated yield based on half of aldehyde.
bConditions: carbonyl compound (1.5 mmol), HMDS (1.2 mmol), and diethyl phosphite (1.2 mmol).
cConditions: carbonyl compound (2 mmol), HMDS (1.2 mmol), and diethyl phosphite (1.2 mmol).
dIsolated yield based on diethyl phosphite.
2
Hz, C6H5), 159.2 (d, JCP = 3.1 Hz, C6H5); IR: 3371,
3300 (NH2) cm−1; MS (70 eV), m/z: 273 (M+), 136
[M P(O)(OEt)2].
Spectral Data for Selected Diethyl
1-Aminophosphonates
Diethyl 1-Aminophenylmethylphosphonate (2).
1H NMR (CDCl3, TMS): δ 1.16 (t, 3H, 2 JHH = 7.0 Hz,
2
Diethyl
1-Amino(p-chlorophenyl)methylphos-
OCH2CH3), 1.26 (t, 3H, JHH = 7.0 Hz, OCH2CH3),
phonate (8). 1H NMR (CDCl3, TMS): δ 1.07 (t,
2.37 (bs, NH2), 3.82–4.09 (m, 4H, OCH2CH3), 4.24
2
2
(d, 1H, 1 JPH = 17.2 Hz, CH), 7.21–7.46 (m, 5H, C6H5);
3H, JHH = 7.0 Hz, OCH2CH3), 1.13 (t, 3H, JHH
= 7.0 Hz, OCH2CH3), 1.82 (bs, NH2), 3.73–3.97
13C NMR (CDCl3, TMS): δ 16.3 (d, JCP = 5.7 Hz,
3
1
3
(m, 4H, OCH2CH3), 4.10 (d, 1H, JPH = 17.2 Hz,
OCH2CH3), 16.4 (d, JCP = 5.7 Hz, OCH2CH3), 54.0
1
2
CH), 7.15–7.19 (m, 2H, C6H4), 7.24–7.27 (m, 2H,
(d, JCP = 149.5 Hz, CH), 62.7 (d, JCP = 7.7 Hz,
OCH2CH3), 62.8 (d, 2 JCP = 7.7 Hz, OCH2CH3), 127.6,
C6H4); 13C NMR (CDCl3, TMS): δ 16.2 (d, JCP = 5.7
3
3
3
2
Hz, OCH2CH3), 16.3 (d, JCP = 5.7 Hz, OCH2CH3),
128.1 (d, JCP = 2.5 Hz, C6H5), 137.3 (d, JCP = 3.8
Hz, C6H5); IR: 3375, 3293 (NH2) cm−1; MS (70 eV),
m/z: 243 (M+), 106 [M P(O)(OEt)2].
1
2
53.3 (d, JCP = 150.3 Hz, CH), 62.6 (d, JCP = 5.1
2
Hz, OCH2CH3), 62.8 (d, JCP = 5.1 Hz, OCH2CH3),
2
128.4, 129 (C6H5), 133.4 (d, JCP = 4.4 Hz, C6H5),
136.3 (d, 3 JCP = 3.7 Hz, C6H5); IR: 3350, 3280 (NH2)
cm−1; MS (70 eV), m/z: 279 (M + 2), 277 (M+), 140
[M P(O)(OEt)2].
Diethyl 1-Amino(p-methoxyphenyl)methylphos-
phonate (5). 1H NMR (CDCl3, TMS): δ 1.16 (t, 3H,
2 JHH = 7.0 Hz, OCH2CH3), 1.26 (t, 3H, JHH = 7.0
2
Hz, OCH2CH3), 1.88 (bs, NH2), 3.78 (s, 3H, OCH3),
3.82–4.08 (m, 4H, OCH2CH3), 4.18 (d, 1H, 1 JPH = 16.2
Hz, CH), 6.85–6.88 (m, 2H, C6H4), 7.33–7.45 (m, 2H,
Diethyl 1-Amino(2-naphthyl)methylphosphonate
(10). 1H NMR (CDCl3, TMS): δ 1.15 (t, 3H, JHH
=
2
3
2
C6H4); 13C NMR (CDCl3, TMS): δ 16.3 (d, JCP = 6.3
7.0 Hz, OCH2CH3), 1.25 (t, 3H, JHH = 7.0 Hz,
3
Hz, OCH2CH3), 16.4 (d, JCP = 6.3 Hz, OCH2CH3),
OCH2CH3), 2.19 (bs, NH2), 3.78–4.10 (m, 4H,
1
1
53.4 (d, JCP = 150.9 Hz, CH), 55.2 (s, OCH3), 62.6
OCH2CH3), 4.43 (d, 1H, JPH = 17.5 Hz, CH), 7.44–
2
2
(d, JCP = 6.9 Hz, OCH2CH3), 62.7 (d, JCP = 6.9 Hz,
7.48 (m, 2H, C10H7), 7.56–7.60 (m, 1H, C10H7),
7.80–7.90 (m, 4H, C10H7); 13C NMR (CDCl3, TMS):
3
OCH2CH3), 128.7, 128.8 (C6H5), 113.8 (d, JCP = 2.5
Heteroatom Chemistry DOI 10.1002/hc

114 Sobhani and Tashrifi
3
3
δ 16.3 (d, JCP = 5.7 Hz, OCH2CH3), 16.4 (d, JCP
=
3377, 3299 (NH2) cm−1; MS (70 eV), m/z: 258 (M+),
121 [M P(O)(OEt)2].
1
5.7 Hz, OCH2CH3), 54.2 (d, JCP = 149.7 Hz, CH),
62.8 (d, 2 JCP = 6.3 Hz, OCH2CH3), 62.9 (d, 2 JCP = 6.3
Hz, OCH2CH3), 125.7–126.6 (m, C10H7), 127.6–128.1
Diethyl
1-Amino-1-ethyl-3-methylbutylphos-
(m, C10H7), 132.9–133.2 (m, C10H7), 135.1 (d, JCP
=
phonate (18). 1H NMR (CDCl3, TMS): δ 0.95 (t,
2
2
3.8 Hz, C10H7); IR: 3371, 3292 (NH2) cm−1; MS (70
6H, JHH = 6.7 Hz, OCH2CH3), 1.23–1.33 (m, 9H,
eV), m/z: 293 (M+), 156 [M P(O)(OEt)2].
CH3), 1.46–1.63 (m, 6H, CH2, NH2), 1.89–1.99 (m,
1H, CH), 4.05–4.17 (m, 4H, OCH2CH3); 13C NMR
3
(CDCl3, TMS): δ 16.6 (d, JCP = 5 Hz, OCH2CH3),
Diethyl
1-Amino(2-thienyl)methylphosphonate
22.1 (d, 3 JCP = 1.9 Hz, CH3), 23.2 (d, 2 JCP = 10.1 Hz,
CH2), 25.2 (s, CH3), 45.5 (d, 3 JCP = 3.1, CH), 52.5 (d,
1 JCP = 145.3 Hz,), 62.2 (d, 2 JCP = 7.5 Hz, OCH2CH3);
IR: 3390, 3302 (NH2) cm−1; MS (70 eV), m/z: 251
(M+), 114 [M P(O)(OEt)2].
(11). 1H NMR (CDCl3, TMS): δ 1.11–1.20 (m,
6H, OCH2CH3), 2.27 (bs, NH2), 3.82–4.03 (m, 4H,
1
OCH2CH3), 4.42 (d, 1H, JPH = 16.7 Hz, CH), 6.87
2
(t, JHH = 4.0 Hz, 1 H, C4H3S), 7.03 (s, 1H, C4H3S),
7.14 (d, 1H, 2 JHH = 5.0 Hz, C4H3S); 13C NMR (CDCl3,
3
TMS): δ 16.3 (d, JCP = 3.8 Hz, OCH2CH3), 16.4 (d,
3 JCP = 3.8 Hz, OCH2CH3), 49.9 (d, JCP = 156.2 Hz,
1
Diethyl
1-Amino-1-methylpropylphosphonate
2
(19). 1H NMR (CDCl3, TMS): δ 0.98 (t, 3H, JHH
=
CH), 62.9 (d, 2 JCP = 7.6 Hz, OCH2CH3), 124.9, 125.5,
2
2
7.5 Hz, CH3), 1.24 (d, 3H, JPH = 16 Hz, CH3), 1.32
126.8 (C4H3S), 141 (d, JCP = 3.8 Hz, C4H3S); IR:
2
3374, 3302 (NH2) cm−1; MS (70 eV), m/z: 249 (M+),
(t, 6H, JHH = 7 Hz, OCH2CH3), 1.59–1.73 (m, 4H,
CH2, NH2); 4.07–4.19 (m, 4H, OCH2CH3); 13C NMR
112 [M P(O)(OEt)2].
3
(CDCl3, TMS): δ 7.3 (d, JCP = 7.6 Hz, CH3), 16.6 (d,
3 JCP = 5.7 Hz, OCH2CH3), 21.7 (d, JCP = 21.7 Hz,
2
Diethyl
1-Amino(2-furyl)methylphosphonate
2
1
CH3), 30.0 (d, JCP = 3.8 Hz, CH2), 52.0 (d, JCP
=
(12). 1H NMR (CDCl3, TMS): δ 1.19 (t, 3H, JHH
2
2
147.4 Hz, C), 62.2 (d, JCP = 7.6 Hz, OCH2CH3); IR:
3378, 3307 (NH2) cm−1; MS (70 eV), m/z: 209 (M+),
72 [M P(O)(OEt)2].
2
= 7.0 Hz, OCH2CH3), 1.26 (t, 3H, JHH = 7.0 Hz,
OCH2CH3), 3.28 (bs, NH2), 3.84–4.13 (m, 4H,
1
OCH2CH3), 4.23 (d, 1H, JPH = 18.3 Hz, CH), 6.10–
6.12 (m, 1H, C4H3O), 6.45–6.47 (m, 1H, C4H3O),
7.33–7.34 (m, 1H, C4H3O); 13C NMR (CDCl3, TMS): δ
16.3 (d, 3 JCP = 5.1 Hz, OCH2CH3), 16.4 (d, 3 JCP = 5.1
Methyl
2-Amino-2-(diethoxyphosphoryl)-
propanoate (20). 1H NMR (CDCl3, TMS): δ 1.33 (t,
2
3
6H, JHH = 7.0 Hz, OCH2CH3), 1.58 (d, 3H, JPH
=
1
Hz, OCH2CH3), 48.2 (d, JCP = 155.0 Hz, CH), 62.8
16.2 Hz, CH3), 2.11 (bs, NH2), 3.78 (s, 3H, CO2CH3),
4.06–4.23 (m, 4H, OCH2CH3); 13C NMR (CDCl3,
2
(d, JCP = 6.9 Hz, OCH2CH3), 110.1, 110.6, 141.8,
151.0 (C4H3O); IR: 3378, 3268 (NH2) cm−1; MS (70
3
TMS): δ 16.5 (d, JCP = 5.0 Hz, OCH2CH3), 21.9 (s,
eV), m/z: 233 (M+), 96 [M P(O)(OEt)2].
CH3), 52.9 (s, CH3), 58.4 (d, 1 JCP = 145.5 Hz, C), 63.4
2
2
(d, JCP = 3.2 Hz, OCH2CH3), 63.5 (d, JCP = 3.2 Hz,
2
Diethyl
1-Amino(1H-3-indolyl)methylphos-
OCH2CH3), 172.2 [d, JCP = 3.8 Hz, C(O)]; IR: 3394,
phonate (13). 1H NMR (CDCl3, TMS): δ 1.24–1.29
3316 (NH2) cm−1; MS (70 eV), m/z: 239 (M+), 102
(m, 6H, OCH2CH3), 3.03 (bs, NH2), 4.09–4.15
[M P(O)(OEt)2].
1
(m, 4H, OCH2CH3), 4.63 (d, 1H, JPH = 15.0 Hz,
CH), 7.04–7.17 (m, 2H, C8H6N), 7.33–7.41 (m, 2H,
C8H6N), 7.63–7.66 (m, 1H, C8H6N), 9.33 (bs, NH);
Diethyl 1-Aminocyclopentylphosphonate (21).
2
1H NMR (CDCl3, TMS): δ 1.29 (t, 6H, JHH = 7.2
13C NMR (CDCl3, TMS): δ 16.3 (d, JCP = 5.7 Hz,
3
Hz, OCH2CH3), 1.54–1.69 (m, 4H, C5H8), 1.87–2.04
(m, 6H, C5H8, NH2), 4.08–4.20 (m, 4H, OCH2CH3);
3
OCH2CH3), 16.2 (d, JCP = 5.7 Hz, OCH2CH3), 45.9
1
2
3
13C NMR (CDCl3, TMS): δ 16.6 (d, JCP = 5.7 Hz,
(d, JCP = 158.7 Hz, CH), 62.9 (d, JCP = 6.3 Hz,
OCH2CH3), 63.4 (d, 2 JCP = 6.3 Hz, OCH2CH3), 110.7,
118.8, 119.5, 119.3, 122.0, 124.3 (C8H6N), 126.1 (1H,
2 JCP = 5.7 Hz, C8H6N), 136.1 (C8H6N); IR: 3396,
3252 (NH2, NH) cm−1; MS (70 eV), m/z: 282 (M+),
145 [M P(O)(OEt)2].
2
OCH2CH3), 24.6 (d, JCP = 11.3 Hz, C5H8), 36.3
3
1
(d, JCP = 6.9 Hz, C5H8), 58.7 (d, JCP = 154.7 Hz,
2
C5H8), 62.2 (d, JCP = 6.9 Hz, OCH2CH3); IR: 3368,
3294 (NH2) cm−1; MS (70 eV), m/z: 221 (M+), 84
[M P(O)(OEt)2].
Diethyl 1-Amino-1-pyridin-4-ylethylphosphonate
Diethyl 1-Aminocyclohexylphosphonate (22). 1H
2
2
(16). 1H NMR (CDCl3, TMS): δ 0.91 (t, 6H, JHH
=
NMR (CDCl3, TMS): δ 1.29 (t, 6H, JHH = 7.2
7.5 Hz, OCH2CH3), 1.28 (d, 3H, 2 JPH = 17.1 Hz, CH3),
1.64 (bs, NH2), 4.19–4.23 (m, 4H, OCH2CH3), 7.50–
7.54 (m, 2H, C5H4N), 7.68–7.72 (m, 2H, C5H4N); IR:
Hz, OCH2CH3), 1.52–1.72 (m, 12H, C6H10, NH2),
4.04–4.15 (m, 4H, OCH2CH3); 13C NMR (CDCl3,
3
TMS): δ 16.5 (d, JCP = 5.7 Hz, OCH2CH3), 19.8 (d,
Heteroatom Chemistry DOI 10.1002/hc

One-Pot Synthesis of Primary 1-Aminophosphonates 115
3 JCP = 11.3 Hz, C6H10), 25.5, 31.3 (C6H10), 51.6 (d, 1 JCP
= 151 Hz, C6H10), 62.1 (d, 2 JCP = 8.2 Hz, OCH2CH3);
IR: 3385, 3290 (NH2) cm−1; MS (70 eV), m/z: 235
(M+), 98 [M P(O)(OEt)2].
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Diethyl 1-Aminocycloheptylphosphonate (23).
2
1H NMR (CDCl3, TMS): δ 1.21 (t, 6H, JHH = 7
Hz, OCH2CH3), 1.42–1.52 (m, 12H, C7H12), 1.90
(bs, NH2), 3.96–4.08 (m, 4H, OCH2CH3); 13C NMR
3
(CDCl3, TMS): δ 16.5 (d, JCP = 5.7 Hz, OCH2CH3),
2
21.9 (d, JCP = 9.4 Hz, C7H12), 30.3 (s, C7H12), 35.5
3
1
(d, JCP = 3.1 Hz, C7H12), 54.5 (d, JCP = 144 Hz,
2
C7H12), 62.1 (d, JCP = 7.5 Hz, OCH2CH3); IR: 3369,
3300 (NH2) cm−1; MS (70 eV), m/z: 249 (M+), 112
[M P(O)(OEt)2].
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2004, 45, 9233–9236.
Diethyl 1-Aminocyclooctylphosphonate (24). 1H
2
NMR (CDCl3, TMS): δ 1.24 (t, 6H, JHH = 7 Hz,
OCH2CH3), 1.34–1.80 (m, 16H, C8H14, NH2), 3.99–
4.11 (m, 4H, OCH2CH3); 13C NMR (CDCl3, TMS): δ
16.5 (d, 3 JCP = 5.7 Hz, OCH2CH3), 21.6 (d, 2 JCP = 8.2
Hz, C8H14), 24.9, 28.1 (C8H14), 30.9 (d, 3 JCP = 3.1 Hz,
C8H14), 54.9 (d, 1 JCP = 144.0 Hz, C8H14), 62.0 (d, 2 JCP
= 7.5 Hz, OCH2CH3); IR: 3368, 3295 (NH2) cm−1; MS
(70 eV), m/z: 263 (M+), 126 [M P(O)(OEt)2].
ACKNOWLEDGMENT
[27] Matveeva, E. D.; Podrugina, T. A.; Tishkovskaya,
E. V.; Tomilova, L. G.; Zefirov, N. S. Synlett 2003,
2321–2324.
The authors are thankful to the Birjand University
Research Council for the support of this work.
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Heteroatom Chemistry DOI 10.1002/hc