Modification of vinylformamide by Michael addition to methyl acrylate and methyl vinyl ketone, and copolymers derived from the resulting products

Article abstract of DOI:10.1023/A:1022237230890

Vinylformamide reacts with methyl acrylate and methyl vinyl ketone under conditions of base catalysis, following the Michael addition pattern, to give methyl 3-(vinylformylamino)propionate and previously unknown 4-(vinylformylamino)-2-butanone. Radical co

Full text of DOI:10.1023/A:1022237230890

Russian Journal of Applied Chemistry, Vol. 75, No. 9, 2002, pp. 1458 1461. Translated from Zhurnal Prikladnoi Khimii, Vol. 75, No. 9,
2002, pp. 1490 1493.
Original Russian Text Copyright
2002 by Ershov, Gavrilova, Panarin.
MACROMOLECULAR CHEMISTRY
AND POLYMERIC MATERIALS
Modification of Vinylformamide by Michael Addition
to Methyl Acrylate and Methyl Vinyl Ketone,
and Copolymers Derived from the Resulting Products
A. Yu. Ershov, I. I. Gavrilova, and E. F. Panarin
Institute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, Russia
Received June 18, 2002
Abstract Vinylformamide reacts with methyl acrylate and methyl vinyl ketone under conditions of base
catalysis, following the Michael addition pattern, to give methyl 3-(vinylformylamino)propionate and previ-
ously unknown 4-(vinylformylamino)-2-butanone. Radical copolymerization of these compounds with vinyl-
formamide and N-vinylpyrrolidone was studied.
Targeted transport of a physiologically active sub-
CH=O
stance to a definite organ, cell, or tissue of a living
CH2=CH N
+ CH2=CH COR
body is an important problem in modern pharmacol-
ogy. Efficient carriers for such transport can be water-
soluble copolymers derived from N-vinylamides,
which show enhanced affinity for proteins owing to
the presence of similar amide groups and other func-
tional moieties.
H
CH=O
CH2=CH N
CH2CH2COR
Ia, Ib
where R = OCH (Ia), CH (Ib).
3
3
Polymers derived from N-vinylpyrrolidone and
N-vinylacetamide and its N-alkyl analogs were studied
previously [1 3]. Introduction of hydrophobic alkyl
radicals into side chains of such polymers opens up
possibilities for control of their conformational state
and increases the probability of their binding with
hydrophobic sections of cell membranes.
We found that the reaction occurs within 24 h at
room temperature without a solvent in the presence
of catalytic amounts of an alkali. The products are
liquids readily distillable in a vacuum. The physico-
chemical characteristics of the compounds are listed
in Table 1.
1
The H NMR spectra of Ia and Ib fully confirm
their structure. In particular, the spectra (Fig. 1a) con-
tain a characteristic ABX pattern of vinyl protons (4.5
and 6.5 ppm) and two multiplets of methylene protons
(2.5 and 4.0 ppm, CH CH N). Some signals are
doubled because of braked rotation of the formyl
group about the C N bond (Table 2).
In this work, with the aim to develop new copoly-
mers based on vinylformamide (VF) and containing
functional fragments in pendant chains, we studied
modification of VF by the reactions with methyl
acrylate (MA) and methyl vinyl ketone (MVK) under
conditions of base catalysis, following the Michael
addition pattern:
2
2
Thus, Michael addition of vinylformamide to com-
Table 1. Physicochemical characteristics of Ia and Ib
Found, %
Calculated, %
Compound
bp, C/P, mm Hg
Formula
Yield, %
C
H
N
C
H
N
Ia
Ib
93 96/2
98 104/1
53.54
59.60
6.97
7.79
8.87 C7H11NO3 53.49
9.88 C7H11NO2 59.56
7.05
7.85
8.91
9.92
70
75
1070-4272/02/7509-1458$27.00 2002 MAIK Nauka/Interperiodica

MODIFICATION OF VINYLFORMAMIDE BY MICHAEL ADDITION
Table 2. 1H NMR spectra of Ia and Ib in CDCl3
1459
, ppm
CH2=, m
Conformational
composition, %
Compound
CH3, s
CH2CO, m
CH2N, m
CH=, m
CH=O, s
Ia
Ib
E, 75
Z, 25
E, 80
Z, 20
3.62
3.62
2.07
2.07
3.80
3.80
2.63
2.63
4.51
4.51
4.41
4.41
6.51
6.49
6.50
6.49
7.18
6.90
7.11
6.91
8.23
8.18
8.20
8.18
pounds containing an activated C=C bond (MA,
MVK) is a convenient route to modified vinylform-
amide derivatives, which are of interest as monomeric
precursors of water-soluble copolymers containing a
functionally substituted vinylamide moiety:
CH2CH2COOH
NH2+ Cl
NH+3Cl
( CH2 CH )n
( CH2 CH )m
CH2CH2COR
IV
HNCH=O
NCH=O
(a)
( CH2 CH )n
( CH2 CH )m
IIa, IIb
CH2CH2COCH3
O
NCH=O
N
( CH2 CH )m
( CH2 CH )
n
III
where R = OCH (IIa), CH (IIb).
, ppm
3
3
(b)
Copolymerization of VF and VP with modified
VF analogs, methyl 3-(vinylformylamino)propionate
(VFMA) and 4-(vinylformylamino)-2-butanone
(VFVMK) was performed by heating of the mono-
mers dissolved in isopropanol at 60 C in glass am-
pules under nitrogen, with azobis(isobutyronitrile)
initiator (1 wt % relative to comonomers). The condi-
tions for preparing copolymers IIa, IIb, and III and
their intrinsic viscosities [ ] are listed in Table 3.
The procedure allows preparation of random water-
soluble copolymers in high yields.
, ppm
The compositions of the copolymers were deter-
mined from the integral intensities of the characteristic
H NMR signals, namely, of those of H C=O (8 ppm)
(c)
1
and CH (2.8 ppm) groups in the case of IIa and IIb
2
(Fig. 1b, Table 4) and of H C=O group (8 ppm) and
5
H atom in the pyrrolidone ring in the case of co-
polymer III derived from VP. The measurement error
was 3 5%.
Copolymers IIa were hydrolyzed to vinylamine
3-(vinylamino)propionic acid copolymers (in the form
of hydrochlorides, IV) by heating in 10% HCl at
120 C for 24 h; the products were isolated by precipi-
tation into acetone.
, ppm
1
Fig. 1. H NMR spectra of (a) Ia in CDCl , (b) IIa in D O,
3
2
and (c) IV in D O. ( ) Chemical shift.
2
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 75 No. 9 2002

1460
Table 3. Copolymerization conditions and characteristics of copolymers
Content of initial monomers, mol % Copolymer composition, mol %
ERSHOV et al.
[ ],
dl g
Compound
Yield, %
1
VF or VP
VFMA or VFVMK
VF or VP
VFMA or VFVMK
IIa
85
50
25
15
50
75
90
60
50
85
60
35
15
40
65
0.27
0.18
0.17
IIb
III
IV
80
65
20
35
95
70
84
62
16
38
0.40
0.18
80
70
20
30
98
75
82
75
18
25
0.21
0.13
85
50
25
15
50
75
65
75
70
85
60
35
15
40
65
0.15
0.12
0.10
Table 4. 1H NMR spectra of copolymers in D2O
, ppm
H C=O or H3, H4, H5
Compound
CH2
CH
CH2CO
CH2N
CH3
IIa
IIb
III
IV
1.97
1.98
2.03
2.21
4.02
4.12
3.97
4.04
8.12 (H C=O)
2.76
3.08
3.13
3.13
3.56
3.61
3.44
3.64
3.78
2.46
2.41
8.20 (H C=O)
2.24 (H4), 2.48 (H3), 3.53 (H5)
The degree of hydrolysis was evaluated from the
Cl content, determined by conductometric titration
eter. The intrinsic viscosity was measured with an
Ubbelohde viscometer in water at 25 C. Compound Ia
was prepared as described in [4].
1
with 0.01 M AgNO , and also from the H NMR
3
spectra (disappearance of the formyl proton signal
at 8.0 ppm and of the methoxy group signal at
2.8 ppm; Fig. 1c). The conditions for synthesis of
copolymers IV and their intrinsic viscosities are given
in Table 3.
4-(Vinylformylamino)-2-butanone Ib. A 35-g
(0.5-mol) portion of VF was added dropwise with
cooling (the temperature was maintained within 20
25 C) to a mixture of 40 g (0.55 mol) of freshly dis-
tilled MVK, 0.56 g of KOH, and 0.01 g of hydroqui-
none in 10 ml of methanol. The mixture was left over-
night at room temperature and, after addition of 0.5 g
of sodium acetate, distilled in a vacuum.
Thus, Michael addition of vinylformamide to com-
pounds containing an activated double bond is a con-
venient route to modified derivatives of this monomer.
The procedure allows introduction into pendant chains
of ester and carbonyl groups for subsequent modifica-
tion by functional binding of physiologically active
substances.
CONCLUSIONS
(1) Michael addition of vinylformamide to methyl
acrylate and methyl vinyl ketone, yielding new mono-
mers, methyl 3-(vinylformylamino)propionate and
4-(vinylformylamino)-2-butanone, was studied.
EXPERIMENTAL
Elemental (C, H, N) analysis was performed with a
Hewlett Packard 185B analyzer. The H NMR spectra
were recorded on a Bruker AC 200 spectrometer.
Titration was performed with a TV-6L-1 conductom-
(2) Copolymers of these monomers with vinyl-
formamide and N-vinylpyrrolidone were prepared, and
their acid hydrolysis was studied. The N-formyl and
ester groups can be quantitatively removed with the
1
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 75 No. 9 2002

MODIFICATION OF VINYLFORMAMIDE BY MICHAEL ADDITION
formation of vinylamine 3-(vinylamino)propionic REFERENCES
1461
acid copolymers in the form of hydrochlorides.
1. Ershov, A.Yu., Gavrilova, I.I., and Panarin, E.F.,
Zh. Prikl. Khim., 1995, vol. 68, no. 9, pp. 1522 1526.
ACKNOWLEDGMENTS
2. Ershov, A.Yu., Gavrilova, I.I., and Panarin, E.F.,
Zh. Prikl. Khim., 1998, vol. 71, no. 11, pp. 1852 1855.
The study was financially supported by the Russian
Foundation for Basic Research (project no. 02-03-
33110).
3. Pavlov, G.M., Korneeva, E.V., Zhumel’, K., et al.,
Zh. Prikl. Khim., 2000, vol. 73, no. 6, pp. 992 996.
4. US Patent 5463110.
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