Addition of secondary amines to alkynephosphonates

Article abstract of DOI:10.1023/B:RUGC.0000018649.77735.cf

Addition of secondary amines to diethyl alkynephosphonates, catalyzed by Cu(I) salts, proceeds regio- and stereospecifically and yields diethyl (E)-2-diethylaminooalkenephosphonates. The E configuration was established by analysis of the vicinal coupling constants between the phosphorus and carbon nuclei in the ¹³C NMR spectra of the reaction products and model compounds: ³J_PC is 6-10 Hz at the cis arrangement of the coupled nuclei and 16 Hz or higher at the trans arrangement. In all the diethyl diethylaminoalkenephosphonates obtained, ³J_PC is about 5 Hz, suggesting cis addition.

Full text of DOI:10.1023/B:RUGC.0000018649.77735.cf

Russian Journal of General Chemistry, Vol. 73, No. 11, 2003, pp. 1729 1737. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 11, 2003,
pp. 1826 1834.
Original Russian Text Copyright
2003 by Panarina, Dogadina, Ionin.
Addition of Secondary Amines to Alkynephosphonates
A. E. Panarina, A. V. Dogadina, and B. I. Ionin
St. Petersburg State Institute of Technology, St. Petersburg, Russia
Received February 5, 2003
Abstract Addition of secondary amines to diethyl alkynephosphonates, catalyzed by Cu(I) salts, proceeds
regio- and stereospecifically and yields diethyl (E)-2-diethylaminooalkenephosphonates. The E configuration
was established by analysis of the vicinal coupling constants between the phosphorus and carbon nuclei in the
3
13C NMR spectra of the reaction products and model compounds: JPC is 6 10 Hz at the cis arrangement of
the coupled nuclei and 16 Hz or higher at the trans arrangement. In all the diethyl diethylaminoalkenephos-
3
phonates obtained, JPC is about 5 Hz, suggesting cis addition.
2-Dialkylaminoalkenephosphonates are interesting
as precursors of difficultly available Horner Emmons
reagents, -keto and -aldo phosphonates [1 3], as
intermediates in the synthesis of various acyclic [4 7]
and heterocyclic compounds [8 14], and as model
compounds in studies of certain biochemical processes
[15].
geometric isomers, while addition of a secondary
amine, diethylamine, to alkynephosphonate yields a
single stereochemical form, E isomer [20].
Addition of primary and secondary amines to
ethynyldiphenylphosphine oxide, catalyzed by butyl-
lithium and yielding the corresponding (E)-2-amino-
vinyldiphenylphosphine oxides, was studied in most
detail [21]. Noncatalyzed addition of primary amines
to alkynyldiphenylphosphine oxides yields a mixture
of the corresponding (E)- and (Z)-aminovinylphos-
phine oxides [22].
Methods for preparing 2-dialkylaminoalkenephos-
phonates were considered in detail in [16], where a
general method was proposed for the synthesis of
2-dialkylaminoalkenephosphonates by the Arbuzov
reaction catalyzed with Ni(II) salts. We suggest an
alternative convenient route to -enamino phospho-
nates: addition of amines across alkynephosphonate
triple bond. This route was studied earlier with a few
examples only.
We found that the reaction of secondary amines
with diethyl alkynephosphonates is noticeably ac-
celerated in the presense of catalytic amounts of Cu(I)
salts. Successful use of CuCl as a catalyst was noted
for addition of primary and secondary amines to
nitriles; the reaction proceeded with a high yield (80
100%) [23].
For example, as far back as 1963, diethyl (E)-2-di-
ethylaminoethenephosphonate was prepared in a high
yield from a mixture of ethynephosphonate and di-
ethylamine; the reaction was accompanied by self-
heating [17]. More recently, it was noted that the reac-
tions of ethynephosphonate with secondary amines
yield mixtures of (E)- and (Z)- -enamino phosphonates
[18]. Propynephosphonate adds secondary amines to
form a mixture of 2-dialkylaminopropenephosphonate
and 2,2-bis(dialkylamino)propanephosphonate in poor
yield (10 15%) [19].
In this work, we studied addition of secondary
amines to diethyl alkynephosphonates in the presence
of catalytic amounts of Cu(I)Cl. With diethyl ethyne-
phosphonate as example, we found that addition of
secondary amines both in the presence and in the
absence of copper(I) salts proceeds as cis addition and
yields exclusively the E isomer of the corresponding
diethyl 2-dialkylaminoethenephosphonate.
(EtO)2PC CH + HNR2
2-Alkylaminoalkenephosphonates were prepared
in [17] by addition of primary amines to alkynephos-
phonates, but they were not isolated pure and were
used in the synthesis of ketimines and aldimines, and
then of unsaturated aldehydes and ketones. -Enamino
phosphonates were subsequently isolated, and their
1H NMR study showed that addition of primary
amines to alkynephosphonates gives a mixture of
O
Ia
O
(EtO)2P
H
H
MeOH, t
C=C
NR2
E
IIa IIc
NR2 = NEt2, N(CH2)5, N[(CH2)2]2O.
1070-3632/03/7311-1729$25.00 2003 MAIK Nauka/Interperiodica

1730
PANARINA et al.
Table 1. Conditions of synthesis, yields, and constants of diethyl (E)-2-(dialkylamino)alkenephosphonates IIa IIm
Method
Comp no.
R
Time, h Yield, %a
bp, C (P, mm)
solvent,
catalyst
NR2
method
IIa
IIb
IIc
IId
IIe
IIf
IIg
IIh
IIi
H
H
H
N(C2H5)2
N(CH2)5
N[(CH2)2]2O
N(CH3)2
N(C2H5)2
N(CH2)5
N[(CH2)2]2O
N(C2H5)2
N(CH2)5
a
b
b
b
a
b
b
a
b
b
a
b
b
EtOH
MeOH
MeOH
0.5
12
18
18
2.5
22
26
9.3
26.5
30
3.5
50
57
42
36
80
72
38
41
45
36
35
64
41
40
38
109 (0.1)
112 (0.1)
163 (0.5)
121 (0.4)
126 (0.1)
170 (0.5)
180 (0.5)
130 (0.1)
156 (0.2)
155 (0.4)
156 (0.1)
160 (0.1)
165 (0.1)
CH3
CH3
CH3
CH3
C2H5
C2H5
C6H5
C6H5
C6H5
C6H5
MeOH, Cu(I)Cl
EtOH, Cu(I)Cl
MeOH, Cu(I)Cl
MeOH, Cu(I)Cl
Et2O, Cu(I)Cl
MeOH, Cu(I)Cl
MeOH, Cu(I)Cl
EtOH, Cu(I)Cl
MeOH, Cu(I)Cl
MeOH, Cu(I)Cl
IIj
IIk
IIl
N(CH3)2
N(C2H5)2
N(CH2)5
IIm
N[(CH2)2]2O
a
1
According to the H NMR spectrum, the products are formed in quantitative yield, but the yields of the isolated products are
considerably lower because of partial saponification and thermolysis during high-temperature distillation.
Secondary amines do not react with substituted di-
ethyl ethynephosphonates in the absence of Cu(I)Cl
at a noticeable rate even on heating in ampule to
120 C. At a higher temperature ( 150 C), the alkyne-
phosphonates polymerize. Addition of catalytic
amounts of copper(I) salts allows the addition under
mild conditions, and the reaction proceeds regio- and
stereospecifically with formation of the corresponding
diethyl (E)-diethylaminooalkenephosphonates
(Table 1).
corresponding diethyl (E)-diethylaminoalkenephos-
phonate and release of Cu(I)Cl (see scheme).
P
R
CuCl
HNR2
C=C
H
NR2
[HNR2 CuCl]
P C CR
CuCl
P C CR
NR2
(EtO)2PC CR + HNR2
P C CR
[HNR2 CuCl]
O
H
Ib Ie
O
MeOH,
Cu(I)Cl
(EtO)2P
H
R
C=C
P = P(O)(OC2H5)2.
NR2
E
IIa IIi
In nonpolar solvents such as carbon tetrachloride
and benzene, no reaction occurred; in polar chloro-
form and isobutyl alcohol, the reaction was slow.
R = Me, Et, Ph, t-Bu; NR2 = NMe2, NEt2, N(CH2)5,
1
1
N[(CH2)2]2O.
According to the H NMR data obtained using H
{31P} NMDR technique, the reaction in chloroform
gives traces of the addition products. In diethyl ether,
methanol, and ethanol, these reactions proceed with
quantitative yield. The similar effect of solvents was
noted in the study of amine addition to alkynedi-
phenylphosphine oxides [22] and nitriles [23] in polar
media.
Presumably, in the first step the amine coordinates
with Cu(I)Cl, which is manifested as strong coloration
of the reaction solution. Then copper in the amine
complex coordinates with the
alkynephosphonate triple bond [24], which promotes
electrons of the
cis addition of the amine and leads to formation of the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

ADDITION OF SECONDARY AMINES TO ALKYNEPHOSPHONATES
1731
As the compounds formed are hygroscopic, it is
necessary to use anhydrous solvents; from the view-
point of ensuring anhydrous conditions, the best
choice is reaction in absolute methanol in sealed
ampules.
stituent at the triple bond. Replacement of Me by Ph
and Et decelerates the addition, and with R = t-Bu
the reaction does not occur at all.
The type of substituent at the phosphorus atom also
affects the course of this reaction. For example,
substitution of alkyl or amide groups for the ester
group decelerates the reaction considerably. Diethyl-
(2-phenylethynyl)phosphine oxide reacts slowly with
formation of diethyl(2-diethylamino-2-phenylethenyl)-
phosphine oxide, and the reaction of phenylethyne-
phosphonic bis(diethylamide) yields no addition
compound. In the case of dimethyl alkynephosphonate,
an ammonium salt is formed, and further addition of
the amine does not occur.
Attempts to perform the reaction without a solvent
with excess amine resulted in extensive tarring and
various transformations of both the addition products
and starting material: cleavage of the P C bond in the
-enamino phosphonate formed, partial replacement
of ethoxy group by diethylamino group, and other
processes.
The reactivity of alkynephosphonates depends
regularly on the electronic and steric effects of sub-
O
R = Et
(EtO)2P
H
Ph
C=C
MeOH,
NR2
Cu(I)Cl
R = NEt2
R = OMe
E
R2PC CPh + HNEt2
CH3O
O
PC CPh
O
+
Et2NO
CH3
The structure of the obtained diethyl diethylamino-
IIm, we used the well-known dependence of the
3
alkenephosphonates IIa IIm was confirmed un-
vicinal coupling constant J on the geometric con-
1
ambiguously by their H, 13C, 31P NMR and IR spec-
figuration of the compound: in alkene derivatives, this
constant is commonly larger for the trans (compared
to cis) arrangement of the nuclei. This trend, known
for H H [26] and H P [25] coupling, was used, in
particular, in our previous studies. However, the steric
dependence of 3JPC, which might be used in this work,
was not studied previously in detail, and data are
available for a few examples only. Therefore, we
synthesized a series of model compounds with known
tra. The IR spectra contain absorption bands at 1560
1
(C=C) and 1215 cm (P=O). The 31P resonance (
23-29 ppm) occurs in the range characteristic oPf
four-coordinate phosphorus atom. The 1H NMR spectra
of enamines IIa IIm show proton signals of CH
groups in the region of 4 ppm (2JHP 9 12 Hz)
(Table 2), but not 5 7 ppm [25], confirming attack of
the amino group at the carbon atom remote from phos-
phorus. The 13C NMR spectra of diethyl diethyl-
aminoalkenephosphonates IIa IIm are characterized
by a significant difference between the chemical shifts
of the C1 (71 84 ppm) and C2 (152 166 ppm) atoms
(Table 3), which is due to high polarization of the
double bond in these compounds. Thus, our results
show that the reaction is regioselective, yielding ex-
clusively 2-amino derivatives.
geometry and measured their 13C NMR spectra
(Table 4).
3
Analysis of the vicinal constants JPC of model
compounds showed that, at trans configuration, these
constants range from 16 to 24 Hz, and at cis configura-
tion, from 6 to 10 Hz (Table 4). Thus, the vicinal 3JPC
constant is stereospecific, and the values for the two
isomers do not overlap. This allows determination of
the geometry at the double bind even when only one
isomer is taken for the study.
Determination of the geometric configuration of
diethyl diethylaminooalkenephosphonates IIa IIm
involved certain problems. For recently prepared di-
ethyl (2-piperidino-2-phenylethene)phosphonate, the
geometry was not determined exactly [16]. To elu-
cidate the structure of -enamino phosphonates IIa
The 13C NMR spectra of diethyl diethylamino-
alkenephosphonates IId IIi show doublets in the
region of 17.0 23.5 ppm of the CH3 and CH2 carbon
3
atoms, with JPC 3 5 Hz. In the spectra of IIj IIm,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

1732
PANARINA et al.
Table 3. 13C NMR data ( C, ppm; J, Hz) for diethyl (E)-2-
Table 2. IR, 1H NMR, and 31P NMR data for diethyl
(E)-2-(dialkylamino)alkenephosphonates (E)-(C2H5O)2
P(O)CHA=C(NR2)HB (IIa IIc) and (E)-(C2H5O)2P(O)
CHA=C(NR2)R (IIa IIm)
(dialkylamino)alkenephosphonates
(E)-(C2H5O)2P(O)
CH=C(NR2)R (IIa IIm)a
Comp.
no.
1JPC
2JPC 3JPC
1H NMR
1
2
3
IR spectrum,
(C=C),
spectrum,
(HA), ppm
,
(2JHP 3JHH, Hz)/
31P NMR
spectrum,
P, ppm
Comp.
no.
IIa
71.5
72.4
75.5
73.8
73.0
76.0
79.2
72.5
75.6
78.5
76.6
81.2
83.9
152.1
153.5
153.6
160.8
158.8
160.1
160.6
164.4
166.0
208.0
209.2
201.3
215.6
217.3
212.7
212.9
217.3
215.7
20.8
20.1
19.3
20.2
21.0
19.3
19.2
21.6
21.7
18.0
17.1
17.4
16.3
1
1
1
1
cm
IIb
IIc
IId
IIe
IIf
IIg
IIh
IIi
(HB), ppm (3JHP, Hz)
17.4
17.2
17.4
17.0
22.3
23.5
4.21
5.01
3.61
2.81
5.11
5.21
7.51
5.61
4.11
4.1
IIa
IIb
IIc
IId
IIe
IIf
IIg
IIh
IIi
1593
1596
1600
1554
1558
1560
1560
1546
1629
1534
1533
1540
1540
3.6(11.5,14.5)/6.8(16.0)
4.1(6.0,14.8)/6.9(15.3)
4.2(12.0,14.5)/6.9(14.8)
3.6 (9.4)
29.2
29.5
27.6
27.2
27.5
27.9
26.0
27.2
27.3
24.1
24.1
24.6
23.1
3.5 (9.8)
3.9 (9.8)
3.8 (9.0)
3.5 (9.8)
3.9 (10.3)
4.1 (9.8)
3.9 (10.3)
4.4 (9.8)
IIj
IIk
IIl
163.6 135.7 215.6
161.2 135.2 217.8
164.1 136.5 214.4
163.8 135.2 212.6
IIj
IIk
IIl
IIm
a
The following numbering of carbon atoms was used:
1
2
3
IIm
4.4 (9.2)
(C H O) P(O)C H=C (X)(R ) ; in the case of R = Ph, by the
2 5 2
3
C
atom is meant the ipso carbon atom of the aromatic ring.
the ipso carbon atoms of aromatic ring resonate at
135.2 136.5 ppm, JPC 4 7.5 Hz (Table 3). That is,
the vicinal coupling constant is small and hence the
-enamino phosphonates obtained can be unambig-
uously identified as the products of cis addition, i.e.,
as E isomers of the corresponding diethyl diethyl-
aminoalkenephosphonates.
presence and in the absence of the lanthanide shift
reagent, shows that the lanthanide shift of the proton
signals of the CH2 and CH3 groups is considerably
larger than that of the signal of CH2 protons in the
amino group. Hence, the amino group is more distant
from the phosphoryl group than the ethyl and methyl
groups and therefore is less affected by the lanthanide.
This confirms the E configuration of the phosphonates
under consideration.
3
The geometry of diethyl 2-dialkylaminopropene-
phosphonates can also be determined from the allyl
4
coupling constant JHP. In diethyl 2-dialkylaminopro-
For comparison of the spectroscopic data, we at-
tempted to prepare authentic diethyl (Z)-2-diethyl-
aminoethenephosphonate by hydrogenation of the
corresponding ynamino phosphonate on Pd/CaCO3.
Similarly to the hydrogenation of other acetylenic
phosphonates [28], we expected formation of diethyl
(Z)-2-diethylaminoethenephosphonate. However, all
the experiments resulted in formation of the same di-
ethyl (E)-2-diethylaminoethenephosphonate with the
spectral characteristics coinciding with those of the
addition compound obtained from diethyl ethynephos-
phonate and diethylamine.
4
penephosphonates IId IIg, JHP is 1.5 Hz, which is
typical of cisoid arrangement; the transoid constant
commonly ranges from 0 to 0.5 Hz [25]. The E con-
figuration of diethyl 2-dialkylaminoethenephospho-
3
3
nates IIa IIc was established from JHH and JHP,
which were 14.5 and 15 16 Hz, respectively (cf.
3
cis
HH
3
trans
HH
3 cis
3 trans
J
10 12,
J
14 17;
J
15 17,
J
HP
HP
45 60 Hz [13, 25]).
The structures of IIe and IIh were confirmed by a
1H NMR study using lanthanide shift reagents. We
used europium tris(1,1,1,2,2,3,3-heptafluoro-7,7-di-
methyl-4,6-octanedionate) Eu(fod)3. The lanthanide
coordinates at the phosphoryl oxygen atom and
induces various shifts of the proton signals depending
on the location of the group relative to the phosphoryl
fragment. Comparison of the 1H NMR data for diethyl
2-diethylaminoprop-1-enephosphonate and diethyl di-
ethylaminobut-1-enephosphonate, obtained in the
O
H2,
(EtO)2P
H
H
Pd/CaCO3
(EtO)2PC CNEt2
C=C
NR2
E
O
IIa
III
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

ADDITION OF SECONDARY AMINES TO ALKYNEPHOSPHONATES
1733
a
Table 4. 13C NMR data ( C, ppm; J, Hz) for model and known compounds (C2H5O)2P(O)CH=C(X)R
No.
R
X
Isomer
1JPC
2JPC
3JPC
1
2
3
1
2
3
4
5
6
7
8
9
Me
Ph
t-Bu
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Ph
H
H
H
Z
Z
Z
E
E
E
E
E
E
E
E
Z
Z
116.8
115.5
113.3
90.0
89.6
89.8
74.5
70.3
72.5
80.6
148.6
147.3
161.2
152.7
155.5
155.2
156.5
159.4
157.4
156.8
159.2
149.3
149.8
158.4
15.6
134.3
33.3
136.5
137.0
136.6
21.3
18.1
18.4
22.4
19.3
188.7
184.2
186.2
205.0
205.5
204.0
213.8
213.1
213.9
128.0
129.0
101.0
98.2
5.0
5.9
4.7
10.4
7.0
6.3
NHCONHPh
NHCONHC3H7
NHCONHPhOCH3
NHBu-t
NHCH2CH=CH2
NHCH(Ph)CH3
NHBu-t
6.1 [4]
6.1 [4]
6.0 [4]
5.2 [14]
4.2 [14]
4.8 [14]
7.0 [14]
5.5 [14]
7.3 [27]
6.9 [27]
6.5
10b
11b
12b
13b
14
NHCH2Ph
H
79.0
122.1
121.6
111.7
16.8
134.6
20.2
0.0
<2
10.7
H
Me
Me
189.5
27.3
24.2
15
Me
Me
Ph
H
Cl
H
Cl
H
E
Z
E
Z
E
Z
Z
Z
Z
Z
Z
Z
Z
E
E
Z
Z
Z
116.3
122.3
113.5
112.7
111.0
111.5
119.4
92.2
91.0
74.9
75.7
72.5
148.9
154.8
147.7
149.6
161.9
163.2
167.4
151.7
153.9
162.8
162.5
163.7
162.9
147.6
147.3
19.4
29.9
134.5
136.6
33.7
40.7
41.3
137.9
138.0
23.3
20.4
22.9
20.4
19.9
134.8
137.1
136.6
136.3
188.6
175.3
191.6
199.1
188.0
196.9
160.5
184.3
183.8
116.0
115.1
191.0
198.7
102.8
103.7
187.3
187.7
186.3
5.0
6.0
6.7
3.2
3.5
2.5
7.5
23.8
19.3
23.7
16.4
20.1
12.5
14.9
19.1 [4]
18.6 [4]
15.1 [14]
15.1 [14]
21.1 [14]
21.0 [14]
18.3 [27]
18.4 [27]
19.6 [13]
19.7 [13]
19.1 [13]
16c
17
18
19
Ph
t-Bu
t-Bu
t-Bu
Ph
20
Cl
Cl
21c
22
NHCONHPh
NHCONHC3H7
NHBu-t
NHCH2Ph
NHBu-t
NHCH2CH=CH2
H
H
NHPh
NHPhCl-4
NHPhCF3-3
23
Ph
24b
25b
26
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
27
70.1
29b
30b
31
123.7
119.1
84.2
84.6
84.2
1.9
3.7
32
33
a
1
2
3
3
The following numbering of carbon atoms was used: (C H O) P(O)C =C X(R ) ; in the case of R = Ph, by the C atom is meant
2
5
2
b
c
the ipso carbon atom of the aromatic ring.
Acid chlorides.
Diphenylphosphine oxide derivatives.
To confirm additionally the structure of the addi-
(EtO)2P(O)CH=CClR + 2Et2NH
[(EtO)2P(O)C CR ]
tion compounds obtained, we synthesized diethyl 2-
diethylaminoprop-1-enphosphonate by reaction of di-
ethyl allenephosphonate with diethylamine in carbon
tetrachloride. The spectral characteristics of the
compound obtained coincided with those of IIe.
IV
Ib, Id
(E)-(EtO)2P(O)CH=C(NEt2)R + [EtNH3]+Cl ,
IId, IIk
R = Me, Ph.
The synthesized -enamino phosphonates IIa IIm
are yellow oily liquids stable in a dry atmosphere.
The 1H NMR spectra of the reaction mixtures,
1
taken using the H {31P} NMDR technique, contain
We also found that diethyl diethylaminooalkene-
phosphonates can be prepared from the corresponding
diethyl 2-chloroalkenephosphonates with formation
of the same diethyl (E)-diethylaminooalkenephos-
phonates, but in a lower yield.
the signals characteristic of the corresponding diethyl
alkynephosphonates. This fact suggests that the first
step of this reaction is HCl elimination with formation
of the corresponding acetylenic compound Ib or Id,
which in the second step adds amine. This reaction
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

1734
PANARINA et al.
also gives diethyl (E)-diethylaminooalkenephospho-
nates. This method is an alternative route to diethyl
diethylaminooalkenephosphonates.
phonates and phosphonamides, which are interesting
as the Horner Emmons reagents.
EXPERIMENTAL
Diethyl diethylaminooalkenephosphonates IId IIm
can be hydrolyzed with formation of the correspond-
ing -keto phosphonates, which are interesting as
Horner Emmons reagents [1 3], as synthetic inter-
mediates [29 31], and as the effective metal extrac-
tants [32].
The IR spectra were recorded on a Specord IR-75
instrument in a thin layer on KBr. The 1H NMR spec-
1
trum recorded using H {31P} NMDR technique was
taken on a Tesla BS-497 instrument (100 MHz), with
1
HMDS as internal reference. The H, 31P, and 13C
NMR spectra were taken on a Bruker AC-200 instru-
ment (internal reference CDCl3, external reference
85% H3PO4, solvent CDCl3). The mass spectra were
taken on a Hewlett Packard-5890II instrument.
(EtO)2P(O)CH=C(NR2)R + H2O (EtO)2P(O)CH2C(O)R ,
IId IIm
Va Vc
R = Me, Et, Ph; NR2 = NMe2, NEt2, N(CH2)5,
N[(CH2)2]2O.
In the experiments we used absolute solvents.
Other chemicals were distilled when necessary. All
the reactions were performed in an argon flow.
Hydrolysis of diethyl 2-dialkylaminoethenephos-
phonates yields phosphonamides, which may be
interesting for pharmacology [33, 34], as interme-
diates in the synthesis of , -unsaturated amides [35],
and as extractants for transplutonium and rare-earth
elements [36, 37]. It is known that several diethoxy-
phosphorylacetamides exhibit strong physiological
activity and have properties of strong system
acaricides [38].
The starting alkynephosphonates were prepared by
procedures described in [17, 42 44]. The physico-
chemical constants of Ia Ie agreed with published
data [45 48].
Diethyl (E)-diethylaminoalkenephosphonates
IIa IIm. a. A solution of 0.01 mol of appropriate
alkynephosphonate and 0.011 mol of secondary amine
in 10 ml of appropriate solvent, and, in some experi-
ments, 0.05 g of Cu(I)Cl were placed in a flask
equipped with a reflux condenser; the mixture was
refluxed for several hours under argon (Table 1). The
(EtO)2P(O)CH=C(NR2)H + H2O
IIa IIc
(EtO)2P(O)CH2C(O)NR2,
1
reaction progress was monitored by H NMR spec-
VIa VIc
troscopy; the reaction was stopped after complete
consumption of the starting alkynephosphonate. Then
the catalyst was filtered off, the solvent was distilled
off, and the residue was distilled in a vacuum (0.1
0.5 mm).
NR2 = NEt2, N(CH2)5, N[(CH2)2]2O.
The structure of -keto phosphonates and phos-
1
phonamides was confirmed by the set the H, 13C, 31
P
NMR and IR data and by comparison of their charac-
teristics with published data [39 41].
b. 0.01 mol of appropriate alkynephosphonate,
0.011 mol of secondary amine, and, when necessary,
0.05 g of Cu(I)Cl in 2 ml of absolute methanol were
heated for several hours in an ampule at 100 110 C
(Table 1). The solvent was distilled off, and the
residue was fractionated in a vacuum (0.1 0.5 mm).
Thus, we suggested a general and convenient
procedure for preparing various diethyl (E)-diethyl-
aminooalkenephosphonates by addition of secondary
amines to diethyl alkynephosphonates in the presence
of catalytic amounts of Cu(I)Cl. New -enamino
phosphonates IIb, IIc, and IIf IIm were prepared.
Addition of secondary amines to diethyl alkynephos-
phonates is shown to proceed regio- and stereoselec-
tively with exclusive formation of diethyl (E)-2-di-
alkylaminoalkenephosphonates. The vicinal constant
3JPC is stereospecific and can be used to determine the
geometry of 2-aminoalkenephosphonates. Alterna-
tively, diethyl diethylaminoalkenephosphonates can be
prepared by reactions of secondary amines with
2-chloroalkenephosphonates; preparative hydrolysis
of diethyl diethylaminoalkenephosphonates can be
used as route to difficultly accessible keto phos-
Diethyl (E)-2-(diethylamino)ethenephosphonate
IIa: bp 109 C (0.1 mm), n2D0 1.5703. IR spectrum
1
(KBr), , cm : 2970, 1593 (C=C), 1246 (P=O), 1020.
1H NMR spectrum, , ppm (CCl4): 1.18 t (6H, CH3),
1.26 t (6H, CH3), 3.11 q (4H, CH2N), 3.62 d.d (1H,
3
2
CH, JHH 14.5, JHP 11.5 Hz), 3.8 q (4H, CH2O),
6.79 d.d (1H, CH, 3JHH 14.5, 3JHP 16.0 Hz). 13C NMR
spectrum, C, ppm: 12.36 (CH3), 15.82 (CH3), 39.97
1
(CH2N), 60.23 (CH2O), 71.7 d (CH, JPC 212.18 Hz),
2
152.09 d (=C JPC 17.56 Hz). 31P NMR spectrum,
P, ppm: 29.14.
Diethyl (E)-2-piperidinoethenephosphonate
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

ADDITION OF SECONDARY AMINES TO ALKYNEPHOSPHONATES
1735
1
2
IIb: bp 112 C (0.1 mm). H NMR spectrum, , ppm:
160.06 d (=C N, JPC 19.33 Hz). 31P NMR spectrum,
P, ppm: 27.85.
1.28 t (6H, CH3), 1.54 m (6H, CH2 piperidine), 3.11 t
(4H, CH2N), 3.97 q (4H, CH2O), 4.14 d.d (1H, CH,
Diethyl (E)-2-morpholinoprop-1-enephos-
phonate IIg: bp 180 C (0.5 mm), n2D0 1.5700. IR
spectrum (KBr), , cm : 2970, 1560 (C=C), 1213
(P=O), 1024. H NMR spectrum, , ppm: 1.12 t (6H,
CH3), 2.02 d (3H, CH3, JHP 2.0 Hz), 2.98 t (4H,
3JHH 14.5, JHP 6 Hz), 6.93 d.d (1H, CH, JHH 14.5,
3JHP 15.25 Hz). 13C NMR spectrum, C, ppm: 15.92
(CH3), 23.83 (p-CH2, piperidine), 24.27 (m-CH2, pi-
peridine), 48.75 (CH2N), 60.33 (CH2O), 72.44 d (CH,
2
3
1
1
4
1JPC 209.2 Hz), 153.44 d (=C N, JPC 20.1 Hz). 31P
2
2
CH2N), 3.53 t (4H, CH2O), 3.8 d (1H, CH, JHP
9.0 Hz), 3.85 q (4H, CH2O). 13C NMR spectrum,
,
NMR spectrum, P, ppm: 29.45.
C
3
ppm: 15.8 (CH3), 16.95 d (CH3, JPC 2.82 Hz), 45.7
(CH2N), 60.29 (CH2O), 65.71 (CH2O, morpholine),
79.19 d (CH, JPC 212.9 Hz), 160.64 d (=C N, JPC
19.17 Hz). 31P NMR spectrum, P, ppm: 26.04.
Diethyl (E)-2-morpholinoethenephosphonate
IIc: bp 163 C (0.5 mm), n2D0 1.5690. IR spectrum
1
2
1
(KBr), , cm : 2970, 1600 (C=C), 1200 (P=O), 1020.
1H NMR spectrum, , ppm: 1.53 t (6H, CH3), 3.08 t
(4H, CH2N), 3.61 t (4H, CH2O), 3.94 q (4H, CH2O),
Diethyl (E)-2-(diethylamino)but-1-enephos-
phonate IIh: bp 130 C (0.1 mm), n2D0 1.5671, d420
3
2
4.18 d.d (1H, CH, JHH 14.8, JHP 12 Hz), 6.9 t (1H,
CH, JHH 14.8, 3JHP 14.8 Hz). 13C NMR spectrum,
,
3
1
C
1.0234. IR spectrum (KBr), , cm : 2970, 1546
ppm: 16.27 (CH3), 42.9 (CH2N), 60.88 (CH2O), 65.97
1
(C=C), 1213 (P=O), 1029. 1H NMR spectrum, , ppm:
0.90 t (6H, CH3), 0.93 t (3H, CH3), 1.07 t (6H, CH3),
2.4 q (2H, CH2), 3.0 q (4H, CH2N), 3.48 d (1H, CH,
(CH2O, morpholine), 75.5 d (CH, JPC 201.31 Hz),
153.62 d (=C N, JPC 19.32 Hz). 31P NMR spectrum,
2
P, ppm: 27.59.
2JHP 9.8 Hz), 3.79 q (4H, CH2O). 13C NMR spectrum,
Diethyl (E)-2-(dimethylamino)prop-1-enephos-
phonate IId: bp 121 C (0.4 mm), n2D0 1.5680. IR
spectrum (KBr), , cm : 2967, 1554 (C=C), 1209
(P=O), 1018. H NMR spectrum, , ppm: 1.18 t (6H,
CH3), 2.09 s (3H, CH3), 2.77 s (6H, CH3), 3.62 d (1H,
CH, JHP 9.41 Hz), 3.89 q (4H, CH2O). 13C NMR
C, ppm: 12.91 (CH3), 13.96 (CH3, Et), 16.37 (CH3),
22.33 d (CH2, Et, JPC 5.1 Hz), 43.3 (CH2N), 60.45
3
1
1
(CH2O), 72.54 d (CH, JPC 217.33 Hz), 164.43 d
1
(=C N, JPC 21.6 Hz). 31P NMR spectrum, P, ppm:
2
27.17.
2
Diethyl (E)-2-piperidinobut-1-enephosphonate
IIi: bp 156 C (0.25 mm), n2D0 1.5780. IR spectrum
(KBr), , cm : 2973, 1629 (C=C), 1233 (P=O), 1013.
1H NMR spectrum, , ppm: 1.21 t (6H, CH3), 1.25 t
(3H, CH3), 1.5 m (6H, CH2, piperidine), 2.57 q (2H,
3
spectrum, C, ppm: 15.91 (CH3), 17.37 d (CH3, JPC
4.23 Hz), 39.29 (CH3), 60.32 (CH2O), 73.84 d (CH,
1
1JPC 215.2 Hz), 160.82 d (=C N, JPC 20.23 Hz). 31P
2
NMR spectrum, P, ppm: 27.22.
Diethyl (E)-2-(diethylamino)prop-1-enephos-
phonate IIe: bp 126 C (0.1 mm), n2D0 1.5699. IR
spectrum (KBr), , cm : 2970, 1558 (C=C), 1213
(P=O), 1029. H NMR spectrum, , ppm: 0.84 t (6H,
CH3), 1.01 t (6H, CH3), 1.92 d (3H, CH3, JHP
2
CH2, Et), 3.08 m (4H, CH2N), 3.85 d (1H, CH, JHP
10.3 Hz), 3.93 q (4H, CH2O). 13C NMR spectrum,
C, ppm: 13.02 (CH3), 16.77 (CH3), 23.46 d (CH3,
3JPC 5.18 Hz), 25.14 (CH2, piperidine), 47.07 (CH2N),
1
1
4
1
60.39 (CH2O), 75.63 d (CH, JPC 215.7 Hz), 165.99 d
2
(=C N, JPC 21.72 Hz). 31P NMR spectrum, P, ppm:
2
1.6 Hz), 2.95 q (4H, CH2N), 3.46 d (1H, CH, JHP
9.81 Hz), 3.71 q (4H, CH2O). 13C NMR spectrum,
C, ppm: 12.66 (CH3), 16.31 (CH3), 17.15 d (CH3,
3JPC 5.0 Hz), 43.79 (CH2N), 60.45 (CH2O), 72.97 d
(CH, 1JPC 217.34 Hz), 158.75 d (=C N, 2JPC 21.0 Hz).
27.25.
Diethyl (E)-2-(dimethylamino)-2-phenylethene-
phosphonate IIj: bp 155 C (0.4 mm), n2D0 1.5700. IR
spectrum (KBr), , cm : 2960, 1534 (C=C), 1200
1
31P NMR spectrum, P, ppm: 27.46.
1
(P=O), 1020. H NMR spectrum, , ppm: 0.97 t (6H,
Diethyl (E)-2-piperidinoprop-1-enephosphonate
IIf: bp 170 C (0.5 mm), n2D0 1.5688. IR spectrum
(KBr), , cm : 2970, 1560 (C=C), 1220 (P=O), 1029.
1H NMR spectrum, , ppm: 1.1 t (6H, CH3), 1.38 m
CH3), 2.63 s (6H, CH3), 3.63 q (4H, CH2O), 4.06 d
(1H, CH, JHP 9.81 Hz), 7.25 m (5H, arom.). 13C
2
1
NMR spectrum, C, ppm: 15.73 (CH3), 39.77 (CH3),
60.11 (CH2O), 78.46 d (CH, JPC 215.55 Hz), 127.41
(m-CH arom.), 128.28 (p-CH arom.), 128.56 (o-CH
1
4
(6H, CH2, piperidine), 1.98 d (3H, CH3, JHP 1.0 Hz),
3
2
arom.), 135.72 d (Ci, arom., JPC 7.45 Hz), 163.63 d
3.02 t (4H, CH2N), 3.87 d (1H, CH, JHP 9.75 Hz),
(=C N, JPC 18.02 Hz). 31P NMR spectrum, P, ppm:
2
3.88 q (4H, CH2O). 13C NMR spectrum, C, ppm:
3
24.06.
15.8 (CH3), 17.42 d (CH3, JPC 3.57 Hz), 23.65
(p-CH2, piperidine), 24.7 (m-CH2, piperidine), 46.69
(CH2N), 60.11 (CH2O), 76.02 d (CH, JPC 212.7 Hz),
Diethyl (E)-2-(diethylamino)-2-phenylethene-
phosphonate IIk: bp 156 C (0.1 mm), n2D0 1.5685,
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

1736
PANARINA et al.
d240 1.0724. IR spectrum (KBr), , cm : 2970, 1533
(C=C), 1200 (P=O), 1029. 1H NMR spectrum, , ppm:
0.75 m (12H, CH3), 2.28 q (4H, CH2N), 3.42 q (4H,
Savignac, P., Tetrahedron Lett., 1987, vol. 28, no. 12,
p. 1263.
1
7. Mohinder, S., Chattha, M.S., and Aguiar, A.M., Jr.,
Tetrahedron Lett., 1971, vol. 12, no. 18, p. 1419.
8. Palacios, F., Ochoa de Retana, A.M., Oyarzabal, J.,
and Ezbelete, J.M., Tetrahedron, 1998, vol. 54, no. 10,
p. 2281.
9. Alikin, A.Yu., Sokolov, M.P., Liorber, B.G., Razu-
mov, A.I., Zykova, T.V., and Zykova, V.V., Zh.
Obshch. Khim., 1981, vol. 51, no. 3, p. 547.
10. Alikin, A.Yu., Sokolov, M.P., Liorber, B.G., Razu-
mov, A.I., Zykova, T.V., Zykova, V.V., and Suleima-
nova, I.N., Zh. Obshch. Khim., 1981, vol. 51, no. 3,
p. 556.
2
CH2O), 3.87 d (1H, CH, JHP 10.3 Hz), 7.0 m (5H,
arom.). 13C NMR spectrum, C, ppm: 11.7 (CH3),
15.16 (CH3), 42.71 (CH2N), 59.3 (CH2O), 76.6 d (CH,
1JPC 217.82 Hz), 126.65 127.54 (m,p-CH arom.),
128.15 (o-CH arom.), 135.2 d (Ci, arom., 3JPC 5.6 Hz),
2
161.18 d (=C N, JPC 17.1 Hz). 31P NMR spectrum,
P, ppm: 24.14. Mass spectrum (electron impact), M
310; m/z (Irel, %): 29 (77.9), 72 (51.7), 103 (51.3),
131 (34.4), 174 (100), 282 (29.3), 310 (60.7).
Diethyl (E)-2-piperidino-2-phenylethenephos-
phonate IIl: bp 160 C (0.1 mm), n2D0 1.5705. IR spec-
1
11. Palacios, F., Ochoa de Retana, A.M., and Oyarzabal, J.,
Tetrahedron Lett., 1996, vol. 37, no. 26, p. 4577.
trum (KBr), , cm : 2970, 1540 (C=C), 1220 (P=O),
1029. H NMR spectrum, , ppm: 1.06 t (6H, CH3),
1
1.55 m (6H, CH2, piperidine), 3.0 m (4H, CH2N),
12. Palacios, F., Aparicio, D., and Garcia, J., Tetrahedron,
2
4.11 q (4H, CH2O), 4.36 d (1H, CH, JHP 9.8 Hz),
1997, vol. 53, no. 8, p. 2931.
7.35 m (5H, arom.). 13C NMR spectrum, C, ppm:
15.82 (m-CH2, piperidine), 15.85 (CH3), 25.23
(p-CH2, piperidine), 48.62 (o-CH2, piperidine), 60.34
13. Palacios, F., Ochoa de Retana, A.M., and Oyarzabal, J.,
Tetrahedron, 1999, vol. 55, no. 18, p. 5947.
1
14. Palacios, F. and Ochoa de Retana, A.M., Tetrahedron,
(CH2O), 81.19 d (CH, JPC 214.4 Hz), 127.63 (m-CH
1999, vol. 55, no. 10, p. 3091.
arom.), 128.33 (p-CH arom.), 128.99 (o-CH arom.),
3
136.45 d (Ci, arom., JPC 4.07 Hz). 31P NMR spec-
15. Lee, S.-L., Hepburn, T.W., Swartz, W.H., Am-
mon, H.L., Mariano, P.S., and Dunaway-Mariano, D.,
J. Am. Chem. Soc., 1992, vol. 114, no. 19, p. 7346.
trum, P, ppm: 24.6.
Diethyl (E)-2-morpholino-2-phenylethenephos-
phonate IIm: bp 165 C (0.1 mm), n2D0 1.5713. IR
16. Kazankova, M.A., Trostyanskaya, I.G., Lutsen-
ko, S.V., and Beletskaya, I.P., Tetrahedron Lett., 1999,
vol. 40, no. 3, p. 559.
1
spectrum (KBr), , cm : 2970, 1540 (C=C), 1220
1
(P=O), 1020. H NMR spectrum, , ppm: 0.97 t (6H,
CH3), 2.87 t (4H, CH2N), 3.55 t (4H, CH2O, mor-
17. Saunders, B.C. and Simpson, P., J. Chem. Soc., 1963,
2
pholine), 3.67 q (4H, CH2O), 4.37 d (1H, CH, JHP
p. 3351.
9.2 Hz), 7.27 m (5H, arom.). 13C NMR spectrum,
,
C
18. Acheson, R.M., Ansel, P.J., and Murray, J.R., J. Chem.
Res. (S), 1986, p. 378.
ppm: 15.67 (CH3), 47.59 (CH2N), 60.38 (CH2O),
1
65.94 (CH2O, morpholine), 83.93 d (CH, JPC
19. Pudovik, A.N., Khusainova, N.G., and Ageeva, A.G.,
212.6 Hz), 127.57 (m-CH arom.), 128.75 (p-CH
arom.), 128.89 (o-CH arom.), 135.24 d (Ci, arom.,
Zh. Obshch. Khim., 1964, vol. 34, no. 12, p. 3938.
2
20. Mohinder, S., Chattha, M.S., and Aguiar, A.M., Jr.,
3JPC 4.07 Hz), 163.77 d (=C N, JPC 16.31 Hz). 31P
J. Org. Chem., 1973, vol. 38, no. 4, p. 820.
NMR spectrum, P, ppm: 23.12.
21. Maerkl, G. and Merkl, B., Tetrahedron Lett., 1983,
vol. 24, no. 52, p. 5865.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003