Zr4+-catalyzed efficient synthesis of α-aminophosphonates

Article abstract of DOI:10.1055/s-2001-18444

Aldimines undergo nucleophilic addition with diethyl phosphite in the presence of a catalytic amount of zirconium tetrachloride at ambient temperature to afford the corresponding α-aminophosphonates in high yields with high selectivity.

Full text of DOI:10.1055/s-2001-18444

PAPER
2277
Zr4+-Catalyzed Efficient Synthesis of -Aminophosphonates1
Synthesis
.
of -Aminop
S
hosphonates . Yadav,* B.V. S. Reddy, K. Sarita Raj, K. Bhaskar Reddy, A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)7170512; E-mail: yadav@iict.ap.nic.in
Received 21 May 2001; revised 11 September 2001
to afford the corresponding -aminophosphonates in high
yields. In all cases, the reactions proceeded smoothly at
ambient temperature with high selectivity. Both aromatic
and aliphatic aldimines produced excellent yields of prod-
ucts. However, the reactions of aliphatic aldimines took
longer reaction time compared to aromatic imines because
of the lower reactivity of aliphatic aldehydes than aromat-
ic. The reactions are clean and complete within 3–7 hours
(Table). The reaction conditions are very mild and the -
aminophosphonates are exclusively formed without the
formation of any undesired side products. In addition to its
simplicity and milder reaction conditions, this method is
even effective with aliphatic and , -unsaturated alde-
hydes, which normally produce low yields due to their in-
trinsic lower reactivity. The present method does not
require any additives or promoters9 to proceed the reac-
tion. Another important feature of this reaction is the sur-
vival of a variety of functional groups such as olefins,
ethers, hydroxyl, methylenedioxy and halides under the
reaction conditions. Similar yields and selectivity was
also obtained with bismuth(III) chloride in acetonitrile.
Several examples illustrating this novel and efficient pro-
tocol for the synthesis of -aminophosphonates are listed
in the Table. Among various Lewis acids such as YbCl3,
YCl3, and LaCl3 used for this transformation, ZrCl4 was
found to be more effective than others in terms of yields
and reaction time.
Abstract: Aldimines undergo nucleophilic addition with diethyl
phosphite in the presence of a catalytic amount of zirconium tetra-
chloride at ambient temperature to afford the corresponding -ami-
nophosphonates in high yields with high selectivity.
Key words: -aminophosphonates, diethyl phosphite, imines, zir-
conium reagents
The synthesis of -aminophosphonates has attracted
much interest because of their biological activity and
structural analogy to -amino acids.2 They also act as pep-
tide mimics,3 enzyme inhibitors,4 haptens of catalytic an-
tibodies,5 antibiotics and pharmacological agents.6 As a
result, a variety of synthetic approaches7 have been devel-
oped for the synthesis of -aminophosphonates. Of these
methods, the nucleophilic addition of phosphites with
imines, catalyzed by an acid or a base is one of the most
convenient methods. Lewis acids8,9 are known to catalyze
these reactions under mild conditions. Recently, lan-
thanide triflates10 are also found to be effective for this
transformation. However, many of these procedures in-
volve stoichiometric amount of catalysts, expensive re-
agents, longer reaction times and low yields of products in
the cases of aliphatic aldehydes and amines. Therefore,
there is a need to develop a convenient and practically po-
tential method for the synthesis of -aminophosphonates.
In this report, we describe a novel and efficient protocol
for the synthesis of -aminophosphonates using a catalyt-
ic amount of zirconium tetrachloride under mild condi-
tions (Scheme).
In summary, we have demonstrated a novel and efficient
protocol for the synthesis of -aminophosphonates using
catalytic amount of zirconium tetrachloride. The method
is effective for aromatic, aliphatic, , -unsaturated alde-
hydes and provides excellent yields of the products, which
makes it useful and attractive process for the synthesis of
-aminophosphonates.
R1
O
P
R1
H
HN
N
ZrCl
4
+
HO P(OEt)2
OEt
OEt
R
R
CH CN, r.t.,
3
2
3
1
-Aminophosphonates 3: General Procedure
A mixture of aldimine 1 (generated in situ from the corresponding
aldehyde and the amine, Table ) (5 mmol), diethyl phosphite 2 (6
mmol) and ZrCl4 (10 mol%) in MeCN (15 mL) was stirred at r.t. for
an appropriate time (Table). After completion of the reaction, as in-
dicated by TLC, the mixture was quenched with H2O (10 mL) and
extracted with EtOAc (2 15 mL). The combined organic layers
were dried (Na2SO4), concentrated in vacuo, and purified by col-
umn chromatography on silica gel (Merck, 100–200 mesh, EtOAc–
hexane, 2:8) to afford pure -aminophosphonate.
Scheme
The treatment of benzaldimine with diethyl phosphite in
the presence of 10 mol% ZrCl4 in acetonitrile resulted in
the formation of -aminophosphonate 3 (R = Ph, R1 = H)
in 93% yield. Several aldimines (generated in situ from al-
dehydes and amines over anhydrous Na2SO4) reacted well
with diethyl phosphite under similar reaction conditions
3a
Oil.
Synthesis 2001, No. 15, 12 11 2001. Article Identifier:
1437-210X,E;2001,0,15,2277,2280,ftx,en;Z05301SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
1H NMR (CDCl3): = 1.17 (t, 3 H, J = 7.1 Hz), 1.30 (t, 3 H, J = 7.1
Hz), 2.18 (s, 3 H), 3.70–3.83 (m, 1 H), 3.95–418 (m, 3 H), 4.70 (dd,

2278
J. S. Yadav et al.
PAPER
Table ZrCl4-Catalyzed Synthesis of -Aminophosphonatesa
3b
Oil.
Entry Aldehyde
Amine
Reaction
Time (h)
Yieldb
(%)
1H NMR (CDCl3): = 1.18 (t, 3 H, J = 6.8 Hz), 1.28 (t, 3 H, J = 6.8
Hz), 3.90-4.18 (m, 4 H), 4.95 (d, 1 H, J = 23. 8 Hz), 6.60–6.78 (m,
3 H), 6.80–6.95 (m, 2 H), 7.10–7.25 (m, 4 H), 8.85 (br s, 1 H, OH).
13C NMR (CDCl3, proton decoupled): = 16.3, 16.5, 47.8, 50.5,
62.2, 63.5, 114.0, 115.8, 118.5, 120.0, 129.2, 130.0, 131.8, 132.1,
151.5, 158.8, 159.3.
a
3.5
5.0
87
90
b
IR (KBr): 3360, 3180, 1620, 1560, 1520, 1203, 1080, 760 cm–1.
EIMS: m/z = 335 (M+), 178, 77, 65, 53.
c
4.5
5.5
89
85
d
Anal. Calcd for C17H22NO4P (335.3): C, 60.89; H, 6.61; N, 4.18; P,
9.24. Found: C, 60.92; H, 6.70; N, 4.22; P, 9.28.
e
f
4.0
4.0
90
92
3c
Liquid.
1H NMR (CDCl3): = 1.15 (t, 3 H, J = 6.9 Hz), 1.28 (t, 3 H, J = 6.9
Hz), 2.30 (s, 3 H), 3.60–3.78 (m, 1 H), 3.95–4.19 (m, 3 H), 4.60 (br
s, 1 H, NH), 4.75 (d, 1 H, J = 23.7 Hz), 6.38 (d, 1 H, J = 7.8 Hz),
6.60 (t, 1 H, J = 7.8 Hz), 6.90 (t, 1 H, J = 7.8 Hz), 7.0 (d, 1 H, J
= 7.8 Hz), 7.25–7.38 (m, 3 H), 7.40–7.50 (m, 2 H).
13C NMR (CDCl3, proton decoupled): = 15.8, 15.9, 16.0, 16.1,
17.2, 54.3, 57.4, 62.9, 63.0, 111.0, 117.8, 122.6, 126.6, 127.3,
127.4, 127.5, 127.6, 127.8, 128.2, 128.3, 129.5, 129.9, 135.6, 135.7,
143.9, 144.2.
g
h
6.0
3.0
85
93
i
4.5
5.0
4.5
6.0
88
90
92
89
IR (KBr): 3314, 2978, 1614, 1512, 1224, 1010, 981.3, 758 cm–1.
EIMS: m/z = 333 (M+), 196, 155, 122, 105, 77, 43.
j
Anal. Calcd for C18H24NO3P (333.4): C, 64.85; H, 7.26; N, 4.20; P,
9.29. Found: C, 64.81; H, 7.30; N, 4.24; P, 9.30.
k
l
3d
Liquid.
1H NMR (CDCl3): = 1.18 (t, 3 H, J = 7.0 Hz), 1.25 (t, 3 H, J = 7.0
Hz), 3.80–3.90 (m, 1 H), 4.05–4.20 (m, 3 H), 4.80 (br s, 1 H, NH),
5.05 (d, 1 H, J = 23.9 Hz), 6.58 (d, 2 H, J = 7.8 Hz), 6.80 (t, 1 H, J
= 7.8 Hz), 6.85 (d, 1 H, J = 7.8 Hz), 7.05 (d, 1 H, J = 7.8 Hz), 7.10
(t, 1 H, J = 7.8 Hz), 7.20 (d, 1 H, J = 7.8 Hz), 9.05 (br s, 1 H, OH).
13C NMR (CDCl3, proton decoupled): = 16.3, 16.5, 46.9, 50.1,
62.5, 63.5, 115.6, 118.5, 120.7 129.2, 130.8, 131.6, 132.5, 150.5,
158.7, 159.5.
m
n
7.0
5.5
4.5
81
85
82
o
p
q
8.0
5.5
78
85
IR (KBr): 3301, 3212, 3080, 1680, 1572, 1246, 1082, 986, 888, 774
cm–1.
EIMS: m/z = 369 (M+), 278, 233, 128, 112, 65, 43.
r
4.5
6.0
90
87
Anal. Calcd for C17H21ClNO4P (369.8): C, 55.22; H, 5.72; Cl, 9.59;
N, 3.79; P, 8.38. Found: C, 55.25; H, 5.70; Cl, 9.62; N, 3.81; P, 8.40.
s
3e
Solid; mp 78–80 °C.
a All products were characterized by 1H NMR, IR and mass spectra.
b Isolated and unoptimized yield.
1H NMR (CDCl3): = 1.16 (t, 3 H, J = 6.9 Hz), 1.25 (t, 3 H, J = 6.9
Hz), 2.30 (s, 3 H), 3.65–3.75 (m, 4 H), 3.80 (s, 6 H), 3.90–4.20), (m,
3 H), 4.70 (d, 1 H, J = 23.8 Hz), 6.40 (d, 1 H, J = 7.8 Hz), 6.65 (t,
1 H,J = 7.8 Hz), 6.80 (d, 1 H, J = 7.8 Hz), 6.90–7.08 (m, 4 H).
13C NMR (CDCl3, proton decoupled): = 15.9, 16.0, 16.2, 20.0,
54.3, 55.4, 55.5, 57.3, 62.7, 62.8, 110.7, 110.8, 110.9, 113.7, 119.9,
120.0, 127.1, 128.1, 129.3, 143.7, 144.0, 148.4, 148.5, 148.8.
IR (KBr): 3323, 2971, 1560, 1515, 1237, 1028, 963, 756 cm–1.
EIMS: m/z = 393 (M+), 256, 210, 151, 118, 91, 65, 41.
1 H, J = 23, 8.1, 7.0 Hz), 5.28 (dd, 1 H, J = 7.0, 2.0 Hz), 6.30 (d, 1
H, J = 7.8 Hz), 6.78 (d, 1 H, J = 7.8 Hz), 7.25–7.50 (m, 6 H).
13C NMR (CDCl3, proton decoupled): = 16.3, 16.5, 56.3, 63.5,
114.0, 118.5 128.0, 128.7, 129.2, 130.0, 136.0, 146.3.
IR (KBr): 3328, 2972, 1618, 1512, 1228, 1012, 968, 758 cm–1.
Anal. Calcd for C20H28NO5P (393.4): C, 61.06; H, 7.17; N, 3.56; P,
7.87. Found: C, 61.10; H, 7.12; N, 3.51; P, 7.90.
EIMS: m/z = 333 (M+), 196, 105, 91, 77, 51, 43.
Anal. Calcd for C18H24NO3P (333.4): C, 64.85; H, 7.26; N, 4.20; P,
9.29. Found: C, 64.81; H, 7.30; N, 4.24; P, 9.30.
Synthesis 2001, No. 15, 2277–2280 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of -Aminophosphonates
EIMS: m/z = 347 (M+), 210, 118, 91, 65, 51.
2279
3f
Solid; mp 102–104 °C.
Anal. Calcd for C19H26NO3P (347.4): C, 65.69; H, 7.54; N, 4.03; P,
8.92. Found: C, 65.72; H, 7.58; N, 4.14; P, 8.93.
1H NMR (CDCl3): = 1.20 (t, 3 H, J = 7.0 Hz), 1.25 (t, 3 H, J = 7.0
Hz), 2.25 (s, 3 H), 3.65–3.75 (m, 1 H), 3.85–4.18), (m, 3 H), 4.45
(br s, 1 H, NH), 4.60 (d, 1 H, J = 24.0 Hz), 5.85 (s, 2 H), 6.30 (d, 1
H, J = 8.0 Hz), 6.57 (t, 1 H, J = 8.0 Hz), 6.70 (d, 1 H, J = 8.0 Hz),
6.80–7.0 (m, 4 H).
13C NMR (CDCl3, proton decoupled): = 16.0, 16.2, 16.3, 17.3,
54.3, 57.3, 63.0, 63.1, 100.9, 107.9, 108.0, 108.1, 108.2, 111.2,
118.0, 121.0, 121.1, 122.8, 126.8, 129.8, 130.0, 144.0, 144.3, 147.2,
147.8.
3j
Oil.
1H NMR (CDCl3): = 1.18 (t, 3 H, J = 7.0 Hz), 1.30 (t, 3 H, J = 7.0
Hz), 3.68 (s, 3 H), 3.95–4.18 (m, 4 H), 4.80 (d, 1 H, J = 23.8 Hz),
6.60–6.70 (m, 5 H), 6.80–6.95 (m, 2 H), 7.10–7.20 (m, 2 H).
13C NMR (CDCl3, proton decoupled): = 16.3, 16.4, 55.4, 55.6,
63.3, 114.1, 118.2, 120.3, 125.1, 127.7, 129.0, 132.6, 146.5, 159.3.
IR (KBr): 3360, 2894, 1680, 1548, 1342, 1080, 969, 732 cm–1.
EIMS: m/z = 349 (M+), 228, 214, 91, 65, 46.
IR (KBr): 3331, 2982, 1603,1507, 1444, 1261,1023, 964, 750 cm–1.
EIMS: m/z = 377 (M+), 240, 118, 65, 51.
Anal. Calcd for C19H24NO5P (377.4): C, 60.47; H, 6.41; N, 3.71; P,
8.21. Found: C, 60.50; H, 6.38; N, 3.69; P, 8.24.
Anal. Calcd for C18H24NO4P (349.4): C, 61.88; H, 6.92; N, 4.01; P,
8.87. Found: C, 61.95; H, 7.03; N, 4.08; P, 8.85.
3g
Oil.
3k
Solid; mp 62–64 °C.
1H NMR (CDCl3): = 1.10 (t, 3 H, J = 7.0 Hz), 1.30 (t, 3 H, J = 7.0
Hz), 1.80 (br s, 1 H, NH), 3.60 (m, 1 H), 3.90 (m, 1 H), 4.15 (m, 2
H), 4.75 (d, 1 H, J = 23.5 Hz), 6.55–6.70 (m, 3 H), 7.0–7.15 (m, 2
H), 7.38–7.50 (m, 2 H) 7.60 (d, 1 H, J = 7.8 Hz), 7.75–7.90 (m, 4
H).
13C NMR (CDCl3, proton decoupled): = 15.6, 15.7, 16.3, 16.4,
50.0, 53.0, 63.2, 113.5, 118.2, 122.9, 125.3, 125.4, 125.5, 126.1,
128.3, 128.4, 128.9, 129.1, 131.4, 131.7, 133.8, 145.9, 146.2.
1H NMR (CDCl3): = 1.50 (t, 3 H, J = 6.8 Hz), 2.18 (t, 3 H, J = 6.8
Hz), 2.35 (s, 3 H), 3.60–3.75 (m, 1 H), 3.85–4.18 (m, 3 H), 4.60 (br
s, 1 H, NH), 4.78 (d, 1 H, J = 24.7 Hz), 6.58 (d, 2 H, J = 8.0 Hz),
6.68 (t, 1 H, J = 8.0 Hz), 7.05–7.18 (m, 4 H), 7.27 (d, 2 H, J = 8.0
Hz).
13C NMR (CDCl3, proton decoupled): = 16.3, 16.5, 21.2, 55.8,
63.3, 113.9, 118.4, 127.7, 129.4, 132.7, 137.7, 146.3, 146.5.
IR (KBr): 3324, 2984, 1604, 1502, 1234, 1020, 971, 748 cm–1.
EIMS: m/z = 333 (M+), 197,142,105,78.
IR (KBr): 3382, 2980, 1720, 1470, 1320, 1240, 1100, 870, 820, 760
cm–1.
FAB Mass: m/z: 369 (M+), 322, 244, 182, 167, 152, 141, 136, 115.
Anal. Calcd for C18H24NO3P (333.4): C, 64.85; H, 7.26; N, 4.20; P,
9.29. Found: C, 64.81; H, 7.30; N, 4.24; P, 9.30.
Anal. Calcd for C21H24NO3P (369.4): C, 68.28; H, 6.55; N, 3.79; P,
8.38. Found: C, 68.24; H, 6.57; N, 3.80; P, 8.42.
3l
Liquid.
3h
1H NMR (CDCl3): = 1.18 (t, 3 H, J = 7.0 Hz), 1.29 (t, 3 H, J = 7.0
Hz), 2.20 (s, 3 H), 3.78 (s, 3 H), 3.80–4.18 (m, 4 H), 4.70 (dd, 1 H,
J = 24, 7.1 Hz), 5.20 (dd, 1 H, J = 7.1, 2.0 Hz), 6.28 (d, 1 H, J
= 7.8 Hz), 6.70–6.90 (m, 3 H), 7.25–7.40 (m, 3 H).
13C NMR (CDCl3, proton decoupled): = 16.3, 16.5, 20.9, 55.7,
62.3, 62.5, 63.2, 113.5, 113.8, 115.0, 118.5, 119.0, 129.2, 131.0,
131.5, 131.7, 134.8, 147.3, 147.8, 160.7.
Oil.
1H NMR (CDCl3): = 1.15 (t, 3 H, J = 6.9 Hz), 1.25 (t, 3 H, J = 6.9
Hz), 3.65 (s, 3 H), 3.60–4.18 (m, 4 H), 4.65 (d, 1 H, J = 24.0 Hz),
6.50 (d, 2 H, J = 8.0 Hz), 6.65 (d, 2 H, J = 8.0 Hz), 7.20–7.38 (m,
3 H), 7.40–7.50 (m, 2 H).
13C NMR (CDCl3, proton decoupled): = 15.6, 15.7, 15.9, 16.0,
20.4, 54.9, 58.0, 62.3, 62.8, 62.9, 113.4, 114.3, 114.8, 121.9, 127.1,
127.3, 127.4, 127.5, 127.6, 127.7, 128.0, 129.5, 132.2, 135.6, 139.8,
140.1,152.
IR (KBr): 3386, 3050, 2980, 1600, 1560, 1272, 1080, 800, 589
cm–1.
EIMS: m/z = 441 (M+), 304, 302, 224, 196, 180, 168, 141, 121, 83,
IR (KBr): 3378, 3080, 2896, 1786, 1506, 1246, 1096, 794, 732
cm–1.
77, 65, 47.
EIMS: m/z = 349 (M+), 292, 212, 168, 134, 81, 45.
Anal. Calcd for C19H25BrNO4P (442.3): C, 51.60; H, 5.70; Br,
18.07; N, 3.17; P, 7.0. Found: C, 51.64; H, 5.72; Br, 18.12; N, 3.20;
P, 6.97.
Anal. Calcd for C18H24NO4P (349.364): C, 61.88; H, 6.92; N, 4.01;
P, 8.87. Found: C, 61.90; H, 6.95; N, 4.08; P, 8.90.
3m
Oil.
3i
Liquid.
1H NMR (CDCl3): = 0.90 (t, 3 H, J = 6.8 Hz), 1.15 (t, 3 H, J = 7.0
Hz), 1.20–1.55 (m, 11 H), 2.40–2.55 (m, 2 H), 3.50 (br s, 1 H, NH),
3.75–4.15 (m, 5 H), 7.30–7.45 (m, 5 H).
13C NMR (CDCl3, proton decoupled): = 11.4, 16.2, 16.7, 29.7,
32.37, 48.4, 48.7, 60.9, 61.2, 62.0, 63.1,128.5, 129.0, 129.5, 129.5,
132.7, 135.7.
1H NMR (CDCl3): = 1.19 (t, 3 H, J = 7.0 Hz), 1.28 (t, 3 H, J = 7.0
Hz), 2.25 (s, 3 H), 2.30 (s, 3 H), 3.60–3.80 (m, 1 H), 4.05–4.18 (m,
2 H), 4.60 (br s, 1 H, NH), 4.70 (d, 1 H, J = 23.8 Hz), 6.38 (d, 1 H,
J = 8.0 Hz), 6.60 (t, 1 H, J = 8.0 Hz), (t, 1 H, J = 8.0 Hz), 7.0 (t, 1
H, J = 8.0 Hz), 7.10 (d, 2 H, J = 8.0 Hz), 7.38 (d, 2 H, J = 8.0 Hz).
13C NMR (CDCl3, proton decoupled): = 15.9, 16.0, 16.1, 16.2,
17.2, 20.8, 54.1, 57.1, 62.9, 63.0, 111.1, 117.7, 122.6, 126.6,127.3,
127.4, 129.0, 129.1, 129.8, 132.5, 132.6, 137.2, 137.3, 144.0, 144.3.
IR (KBr): 3368, 3270, 2848, 1768, 1460, 1338, 1242, 1050, 732.4
cm–1.
EIMS: m/z = 327 (M+), 190, 105, 77, 65, 51.
IR (KBr): 3397, 3008, 1680, 1540, 1260, 1080, 971.2, 762, 560
cm–1.
Synthesis 2001, No. 15, 2277–2280 ISSN 0039-7881 © Thieme Stuttgart · New York

2280
J. S. Yadav et al.
PAPER
Anal. Calcd for C17H30NO3P (327.4): C, 62.37; H, 9.24; N, 4.28; P,
9.46. Found: C, 62.40; H, 9.20; N, 4.31; P, 9. 47.
3r
Solid; mp 64–66 °C.
1H NMR (CDCl3): = 1.18 (t, 3 H, J = 6.9 Hz), 1.28 (t, 3 H, J = 6.9
Hz), 2.28 (s, 3 H), 3.60–3.75 (m, 1 H), 3.78 (s, 3 H), 3.85–4.18 (m,
3 H), 4.55 (br s, 1 H, NH), 4.70 (d, 1 H, J = 23.7 Hz), 6.38 (d, 1 H,
J = 7.8 Hz), 6.60 (t, 1 H, J = 7.8 Hz), 6.80–7.05 (m, 4 H), 7.38 (d,
2 H, J = 7.8 Hz).
13C NMR (CDCl3, proton decoupled): = 15.7, 15.9, 16.0, 16.1,
17.0, 53.5, 54.6, 56.6, 62.6, 62.7, 111.0, 113.6, 113.7, 117.6, 122.4,
126.5, 127.3, 128.3, 128.4, 129.7, 143.8, 144.1, 158.9.
3n
Liquid.
1H NMR (CDCl3): = 1.12 (t, 3 H, J = 7.0 Hz), 1.28 (t, 3 H, J = 7.0
Hz), 1.30–1.85 (m, 1 H), 8.63 (dd, 1 H, J = 19.0, 2.0 Hz), 3.95–4.15
(m, 4 H), 6.65–7.15 (m, 5 H). 13C NMR (CDCl3, proton decoupled):
= 16.4, 22.0, 27.0, 28.3, 29.7, 31.0, 39.9, 56.1, 62.6, 113.2, 117.8,
129.3, 129.7, 147.8.
IR (KBr): 3324, 2980, 2750, 1760, 1618, 1490, 1228, 960, 830, 780,
550 cm–1.
EIMS: m/z = 325 (M+), 188, 97, 77, 65, 43.
IR(KBr): 3386, 3012, 2860, 1680, 1560, 1280, 1068, 973, 783, 572
cm–1.
EIMS: m/z = 363 (M+), 226, 182, 91, 65, 43.
Anal. Calcd for C17H28NO3P (325.4): C, 62.75; H, 8.67; N, 4.30; P,
9.52.Found: C, 62.71; H, 8.71; N, 4.29; P, 9.55.
Anal. Calcd for C19H26NO4P (363.4): C, 62.80; H, 7.21; N, 3.85; P,
8.52. Found: C, 62.83; H, 7.19; N, 3.87; P, 8.50.
3o
Oil.
3s
Solid; mp 78–80 °C.
1H NMR (CDCl3): = 1.23–1.38 (m, 6 H), 2.25 (s, 3 H), 3.18 (br s,
1 H, NH), 4.15–4.22 (m, 4 H), 4.45 (dd, 1 H, J = 2.15, 2.1 Hz),
6.18–6.35 (m, 1 H), 6.58–6.65 (m, 3 H), 6.85–6.95 (m, 2 H), 7.20–
7.38 (m, 4 H).
13C NMR (CDCl3, proton decoupled): = 16.3, 20.1, 52.7, 55.7,
62.7, 62.8, 63.2, 113.8, 123.5, 126.3, 127.5, 128.3, 129.5, 132.6,
132.9, 136.1, 143.9.
1H NMR (CDCl3): = 1.80 (t, 3 H, 7.0 Hz), 1.29 (t, 3 H, J = 7.0
Hz), 2.18 (s, 3 H), 2.37 (s, 3 H), 3.70–3.85 (m, 1 H), 3.90–4.18 (m,
3 H), 4.70 (dd, 1 H, J = 24, 7.1 Hz), 5.20 (dd, 1 H, 7.1, 2.0 Hz), 6.30
(d, 1 H, J = 7.8 Hz), 6.80 (d, 1 H, J = 7.8 Hz), 7.10 (d, 2 H, J = 7.8
Hz), 7.20–7.38 (m, 3 H).
13C NMR (CDCl3, proton decoupled): = 16.3, 16.5, 20.8, 21.3,
59.3, 62.5, 62.8, 63.0, 114.0, 118.5 129.4, 129.7, 130.0, 130.4,
135.0, 136.4, 146.3, 147.9.
IR (KBr): 3306, 2984, 2922, 1615, 1591, 1238, 1026, 967, 808, 702
cm–1.
EIMS: m/z = 360 (M+), 222, 196, 97, 91, 83, 69, 55, 43.
IR (KBr): 3397, 1515, 1254, 1022, 973 cm–1.
EIMS: m/z = 425 (M+), 289, 273, 193, 154, 140, 91, 43.
Anal. Calcd for C20H26NO3P (359.4): C, 66.84; H, 7.29; N, 3.90; P,
8.62. Found: C, 66.81; H, 7.33; N, 3.93; P, 8.60.
Anal. Calcd for C19H25NO3P (426.3): C, 53.53; H, 5.91; Br, 18.74;
N, 3.29; P, 7.27. Found: C, 53.50; H, 5.93; N, 3.27; P, 7.30.
3p
Oil.
References
1H NMR (CDCl3): = 0.95 (t, 3 H, J = 6.8 Hz), 1.15 (t, 3 H, J = 7.0
Hz), 1.17–1.60 (m, 20 H), 3.85–4.40 (m, 7 H), 7.35–7.48 (m, 5 H).
13C NMR (CDCl3, proton decoupled): = 14.1, 16.7, 22.7, 29.0,
29.3, 29.7, 30.5, 31.8, 32.3, 38.2, 53.7, 61.8, 127.1, 127.7, 128.7,
129.8, 144.4.
(1) IICT Communication No. 10806.
(2) (a) Fields, S. C. Tetrahedron 1999, 55, 12237. (b) Fields, E.
K. J. Am. Chem. Soc. 1952, 74, 1528. (c) Redmore, D. J.
Org. Chem. 1978, 43, 992.
(3) Kafarski, P.; Lejczak, B. Phosphorous Sulfur Silicon Relat.
Elem. 1991, 63, 1993.
(4) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M.
J. Med. Chem. 1989, 32, 1652.
(5) Hirschmann, R.; Smith, A. B. III.; Taylor, C. M.; Benkovic,
P. A.; Taylor, S. D.; Yager, K. M.; Spengler, P. A.;
Venkovic, S. J. Science 1994, 265, 234.
IR (KBr): 3352, 3280, 2850, 1786, 1460, 1320, 1224, 1050, 720
cm–1.
EIMS: m/z = 383 (M+), 246, 139, 107, 91, 77, 51, 43.
Anal. Calcd for C21H38NO3P (383.5): C, 65.77; H, 9.99; N, 3.65; P,
8.05. Found: C, 65.81; H, 9.97; N, 3.68; P, 8.07.
(6) (a) Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. J. Chem.
Soc., Perkin Trans 1 1984, 2845. (b) Atherton, F. R.;
Hassall, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29.
(7) (a) Kukhar, V. P.; Solodenko, V. A. Rus. Chem. Rev (Engl.
Trans) 1987, 56, 859. (b) Yokomatsu, T.; Yoshida, Y.;
Shibuya, S. J. Org. Chem. 1994, 59, 7930. (c) Redmore, D.
Topics in Phosphorus Chemistry, Vol. 8; Griffith, E. J.;
Grayson, M., Eds.; Wiley: New York, 1976, 515.
(8) Laschat, S.; Kunz, H. Synthesis 1992, 90.
(9) (a) Zon, J. Pol. J. Chem. 1981, 55, 643. (b) Chem. Abstr.
1982, 96, 199793. (c) Ranu, B. C.; Hajra, A.; Jana, J. Org.
Lett. 1999, 1, 1141.
(10) (a) Qian, C.; Huang, J. J. Org. Chem. 1998, 63, 4125.
(b) Manabe, K.; Kobayashi, S. Chem. Commun. 2000, 669.
3q
Solid; mp 76–78 °C.
1H NMR (CDCl3): = 1.15 (m, 3 H J = 7.0 Hz), 1.28 (m, 3 H, J
= 6.8 Hz), 2.25 (br s, 1 H, NH), 3.50 (d, 1 H, J = 11.8 Hz), 370–
4.15 (m, 6 H), 7.20–7.45 (m, 6 H), 7.20–7.45 (m, 10 H).
13C NMR (CDCl3, proton decoupled): = 16.1, 16.2, 16,3, 16.4,
19.8, 55.5, 57.0, 63.1, 63.3, 63.4, 110.3, 112.5, 127.5, 127.6, 127.8,
127.9, 128.4, 128.5, 128.7, 132.7, 135.3, 135.4, 140.8, 141.0.
IR (KBr): 3376, 3112, 2904, 1640, 1536, 1296, 1082, 962, 796, 562
cm–1.
EIMS: m/z = 411 (M+), 276, 274, 196, 155, 137, 109, 91, 77, 51, 43.
Anal. Calcd for C18H23NO3P (412.3): C, 52.44; H, 5.62; Br, 19.38;
N, 3.40; P, 7.51. Found: C, 52.43; H, 5.65; Br, 19.37; N, 3.43; P,
7.54.
Synthesis 2001, No. 15, 2277–2280 ISSN 0039-7881 © Thieme Stuttgart · New York