Acylation of aryl-substituted bis(aminomethyl)phosphinic acids

Full text of DOI:10.1007/s11176-008-2027-5

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 2, pp. 324 326.
Original Russian Text A.A. Prishchenko, M.V. Livantsov, O.P. Novikova, L.I. Livantsova, E.R. Milaeva, 2008, published in Zhurnal Obshchei Khimii,
2008, Vol. 78, No. 2, pp. 339 341.
Pleiades Publishing, Ltd., 2008.
LETTERS
TO THE EDITOR
Acylation of Aryl-substituted Bis(aminomethyl)phosphinic Acids
A. A. Prishchenko, M. V. Livantsov, O. P. Novikova,
L. I. Livantsova, and E. R. Milaeva
Lomonosov Moscow State University,
Vorob’evy Gory, Moscow, 119992 Russia
e-mail: liv@org.chem.msu.su
Received May 18, 2007
DOI: 10.1134/S1070363208020278
Phosphorus-substituted carboxamides of various
structure are widely used in organic synthesis and
present certain interest as effective ligands and bio-
logically active compounds [1]. In the present work
we propose convenient methods for preparing a
number of phosphorus-substituted amides of acetic
and oleic [(Z)-octadec-9-enoic] acids on the basis of
recently synthesized arylsubstituted bis(aminomethyl)-
phosphinic acids [2]. Phosphorus-substituted acet-
amides II were prepared in high yields by heating a
mixture of amine I with excess acetic anhydride
followed by treatment of the reaction mixture with
water and recrystallization of the product aqueous
ethanol.
(1) Ac2O; (2) H2O
HOP[C1H(NH)Ar]2
HOP[C1H(NAc)Ar]2,
AcOH
X
O
X
O
Ia Ic
IIa IIc
Bu-t
3
4
3
4
3
2
7
8
4
2
5
2
6
5
5 (a),
Ar =
(c).
9
OMe (b),
OH (c); X = Me (a, b),
Bu-t
The reaction of amines I with excess oleoyl chlo-
ride in the presence of pyridine under the same condi-
tions gave phosphorus-substituted oleamides III in
high yield.
(1) RC(O)Cl, Py; (2) H2O
Ia Ic
HOP{C1H[NC(O)R]Ar}2,
Py HCl
X
O
IIIa IIIc
Bu-t
3
4
3
4
3
4
2
5
2
2
5
R = (CH2)7
H
5 (a),
(CH2)7CH3; Ar =
H
OMe (b),
OH (c);
Bu-t
7
6
8
(c).
9
X = Me (a, b),
324

ACYLATION OF ARYL-SUBSTITUTED BIS(AMINOMETHYL)PHOSPHINIC ACIDS
325
Bis-amines Ia and Ib we described earlier [2] but
bis-amine Ic was specially prepared by an analogous
method. The synthesized compounds Ic III are
promising ligands and biologically active substances,
for example, antioxidants, and phosphorus-substituted
oleamides III can also be applied as micelle-forming
agents.
98 Hz), 130.06 d (C2, 2JPC3 5 Hz), 128.0 129.0 m (C3,
C4, C5), 170.86 d (C=O, JPC 5 Hz), 33.80 s (MeN),
22.03 s (MeC). 31P NMR spectrum, P, ppm: 37.12 s.
1
Second isomer, H NMR spectrum, H, ppm: 5.04 d
2
(C1H, JPH 16 Hz), 2.98 s (MeN), 7.0 7.6 m (C6H5),
1.80 s (Ac). 13C NMR spectrum, C, ppm: 54.28 d
1
2
(C1, JPC 100 Hz), 129.96 d (C2, JPC 4 Hz), 128.0
129.0 m (C3, C4, C5), 171.13 d (C=O, JPC 4 Hz),
33.32 s (MeN), 21.70 s (MeC). 31P NMR spectrum,
P, ppm: 35.88 s. Found, %: C 61.68; H 6.52.
C20H25N2O4P. Calculated, %: C 61.85; H 6.49.
3
The NMR spectra of compounds Ic III show,
together with characteristic signals of the PC1HN
fragments, signals of aromatic and acetyl or oleoyl
fragments (vide infra). According to the NMR spectra,
compounds Ic III are mixtures of two stereoisomers
whose ratio was determined from the 31P NMR spec-
tra (data for the prevailing isomer are given first).
Because of the low contents of the second isomer in
phosphinate IIb, we present for it 31P NMR data only
(cf. [3]).
Compounds IIb and IIc were synthesized by the
same procedure.
Bis[(4-methoxyphenyl)(N-methyl-N-acetyl-
amino)methyl]phosphinic acid (IIb). Yield 86%, mp
1
89 C. First isomer (75%), H NMR spectrum,
,
H
ppm: 5.96 d (C1H, JPH 16 Hz), 6.88 d (C3H, JHH
8 Hz), 7.43 d (C4H, 3JHH 8 Hz), 3.06 s (MeN), 3.74 s
2
3
Bis[(3,5-di-tert-butyl-4-hydroxyphenyl)(N-
phenylamino)methyl]phosphinic acid (Ic) was prep-
ared as described in [2], yield 87%, mp 181 C. First
(MeO), 2.00 s (Ac). 13C NMR spectrum, C, ppm:
53.60 d (C1, JPC 100 Hz), 131.39 d (C2, JPC 7 Hz),
1
2
1
isomer (65%), H NMR spectrum, H, ppm: 1.28 s
131.58 d (C3, 3JPC3 6 Hz), 114.16 s (C4), 159.17 s (C5),
(Me3C), 4.44 d (C1H, 2JPH 16 Hz), 7.19 s (C3H), 6.3
7.0 m (C6H5). 13C NMR spectrum, C, ppm: 30.91 s
170.63 d (C=O, JPC 4 Hz), 33.53 s (MeN), 55.47 s
(MeO), 22.04 s (MeC). 31P NMR spectrum, P, ppm:
1
(Me3C), 34.96 s (Me3C), 55.13 d (C1, JPC 101 Hz),
1
37.70 s. Second isomer. H NMR spectrum, H, ppm:
127.73 s (C2), 124.99 s (C3), 138.91 s (C4), 153.24 s
(C5), 148.38 d (C6, 3JPC 13 Hz), 113.96 s (C7), 128.99
s (C8), 116.90 s (C9). 31P NMR spectrum, P, ppm:
6.02 d (C1H, JPH 16 Hz), 6.91 d (C3H, JHH 8 Hz),
7.50 d (C4H, 3JHH 8 Hz), 2.98 s (MeN), 3.70 s (MeO),
1.91 s (Ac). 13C NMR spectrum, C, ppm: 53.40 d
(C1, 1JPC 100 Hz), 130.79 d (C2, 2JPC 8 Hz), 131.92 d
(C3, 3JP3C 6 Hz), 114.31 s (C4), 158.95 s (C5), 170.77 d
2
3
1
40.06 s. Second isomer. H NMR spectrum, H, ppm:
2
1.32 s (Me3C), 4.77 d (C1H, JPH 16 Hz), 7.13 s
(C3H), 6.3 7.0 m (C6H5). 13C NMR spectrum,
,
C
(C=O, JPC 4 Hz), 33.27 s (MeN), 55.47 s (MeO),
21.55 s (MeC). 31P NMR spectrum, P, ppm: 36.26 s.
Found, %: C 58.72; H 6.59. C22H29N2O6P. Calculated,
%: C 58.92; H 6.52.
ppm: 30.80 s (Me3C), 34.87 s (Me3C), 55.28 d (C1,
1JPC 98 Hz), 127.73 s (C2), 125.24 s (C3), 139.00 s
(C4), 153.38 s (C5), 148.16 d (C6, 3JPC 12 Hz), 113.83
s (C7), 129.56 s (C8), 117.36 s (C9). 31P NMR spec-
trum, P, ppm: 39.65 s. Found, %: C 73.52; H 8.26.
C42H57N2O4P. Calculated, %: C 73.66; H 8.39.
Bis[(3,5-di-tert-butyl-4-hydroxyphenyl)(N-
phenyl-N-acetylamino)methyl]phosphinic acid
1
(IIc). Yield 74%, mp 139 C. First isomer (97%), H
2
NMR spectrum, H, ppm: 6.35 d (C1H, JPH 16 Hz),
Bis[(N-acetyl-N-methylamino)(phenyl)methyl]-
phosphinic acid (IIa). A mixture of 3.1 g of amine
Ia, 15 ml of acetic anhydride, and 20 ml of methylene
chloride was heated under reflux with stirring for 2 h,
after which 20 ml of water was added, and the mix-
ture was heated to boil. The solvents were then
removed in a vacuum. Water, 20 ml, 5 ml of ethanol,
and 5 ml of ether were added to the residue, and the
mixture was stirred for 0.5 h. Ether was separated, and
the crystals were filtered off, washed with ether, and
exposed to a vacuum of 1 mm Hg for 1 h to obtain
3.2 g (82%) of compound IIa, mp 96 C. First isomer
6.7 7.7 m (C6H2, C6H5), 2.03 s (Ac), 1.24 s (2t-Bu).
1
13C NMR spectrum, C, ppm: 58.12 d (C1, JPC
104 Hz), 127 139 m (C6H2, C6H5), 153.94 s (C5),
119.43 s (C7), 123.35 s (C9), 169.19 s (C=O), 34.69 s
(Me3C), 30.60 s (Me3C), 23.68 s (MeC). 31P NMR
spectrum, P, ppm: 34.65 s. Second isomer. 31P NMR
spectrum, P, ppm: 34.35 s. Found, %: C 71.64; H
8.07. C46H61N2O6P. Calculated, %: C 71.85; H 8.00.
Bis[(N-methyl-N-oleoylamino)(phenyl)methyl]-
phosphinic acid (IIIa). To a cooled (10 C) and
stirred mixture of 3.1 g of amine Ia, 5 ml of pyridine,
and 30 ml of methylene chloride, 7.7 g of oleoyl
chloride in 10 ml of methylene chloride was added.
The mixture was heated for 3 h and leaft to stand for
1
(69%), H NMR spectrum, H, ppm: 6.03 d (C1H,
2JPH 16 Hz), 3.07 s (MeN), 7.0 7.6 m (C6H5), 1.99 s
(Ac). 13C NMR spectrum, C, ppm: 54.51 d (C1, 1JPC
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 2 2008

326
PRISHCHENKO et al.
12 h. The precipitate was filtered off. The filtrate was
diluted with 20 ml and heated for 1 h. The solvents
were then removed in a vacuum. Water, 20 ml, 10 ml
of hexane, and 3 ml of ether were added to the residue,
and the mixture was stirred for 0.5 h. Hexane was
separated and water was distilled off in a vacuum of
1 mm Hg for 1 h to obtain 4.9 g (78%) of compound
Bis[(3,5-di-tert-butyl-4-hydroxyphenyl)(N-
phenyl-N-oleoylamino)methyl]phosphinic acid
1
(IIIc). Yield 72%, oil. First isomer (65%), H NMR
2
spectrum, H, ppm: 5.98 d (C1H, JPH 16 Hz), 6.8
7.6 m (C6H2, C6H5), 5.2 5.3 m (CH=CH), 1.1 2.0 m
(14CH2, 2t-Bu), 0.78 t (MeCH2, 3JHH 8 Hz). 13C NMR
1
spectrum, C, ppm: 60.29 d (C1, JPC 102 Hz), 127
1
IIIa as an oil. First isomer (73%), H NMR spectrum,
139 m (C6H2, C6H5, CH=CH), 153.83 s (C5), 119.49 s
(C7), 122.86 s (C9), 174.69 s (C=O), 34.04 s (Me3C),
22 32 m (14CH2, 2Me3C), 14.08 s (Me3C). 31P NMR
H, ppm: 6.23 d (C1H, 2JPH 16 Hz), 7.0-7.6 m (C6H5),
5.25 5.40 m (CH=CH), 3.12 s (MeN), 1.3 2.0 m
3
(14CH2), 0.90 t (MeCH2, JHH 8 Hz). 13C NMR spec-
1
spectrum, P, ppm: 35.11 s. Second isomer. H NMR
1
trum, C, ppm: 54.38 d (C1, JPC 98 Hz), 128.0
2
spectrum, H, ppm: 6.09 d (C1H, JPH 16 Hz), 6.8
131.0 m (C6H5, CH=CH), 172.56 s (C=O), 33.66 s
7.6 m (C6H2, C6H5), 5.2 5.3 m (CH=CH), 1.1 2.0 m
(MeN), 22 32 m (14CH2), 13.59 s (MeC). 31P NMR
(14CH2, 2t-Bu), 0.78 t (MeCH2, 3JHH 8 Hz). 13C NMR
1
spectrum, P, ppm: 35.95 s. Second isomer. H NMR
1
2
spectrum, C, ppm: 60.40 d (C1, JPC 100 Hz), 127
spectrum, H, ppm: 6.31 d (C1H, JPH 16 Hz), 7.0
139 m (C6H2, C6H5, CH=CH), 153.58 s (C5), 119.49 s
(C7), 122.86 s (C9), 174.11 s (C=O), 34.15 s (Me3C),
22 32 m (14CH2, 2Me3C), 14.08 s (MeCH2). 31P
NMR spectrum, P, ppm: 36.77 s. Found, %: C 74.89;
H 9.03. C62H91N2O6P. Calculated, %: C 75.12;
H 9.25.
7.6 m (C6H5), 5.25 5.40 m (CH=CH), 3.07 s (MeN),
3
1.3 2.0 m (14CH2), 0.90 t (MeCH2, JHH 8 Hz). 13C
1
NMR spectrum, C, ppm: 53.94 d (C1, JPC 103 Hz),
126.0 131.0 m (C6H5, CH=CH), 172.72 s (C=O),
33.66 s (MeN), 22 32 m (14CH2), 13.59 s (MeC). 31P
NMR spectrum, P, ppm: 33.38 s. Found, %: C 70.65;
H 8.94. C36H55N2O4P. Calculated, %: C 70.79;
H 9.07.
The NMR spectra were recorded on a Bruker
Avance 400 spectrometer in (CD3)2SO against TMS
(1H, 13C) or 85% solution of H3PO4 in D2O (31P).
Compounds IIIb and IIIc were prepared by the
same method.
ACKNOWLEDGMENTS
Bis[(4-methoxyphenyl)(N-methyl-N-oleoylami-
no)methyl]phosphinic acid (IIIb). Yield 80%, oil.
First isomer (60%), 1H NMR spectrum, H, ppm:
The work was financially supported by the Russian
Foundation for Basic Research (project no. 05-03-
32864).
2
3
6.06 d (C1H, JPH 16 Hz), 6.70 d (C3H, JHH 8 Hz),
7.45 d (C4H, 3JHH 8 Hz), 5.2 5.3 m (CH=CH), 3.06 s
(MeN), 3.65 s (MeO), 1.2 2.0 m (14CH2), 0.82 t
3
REFERENCES
(MeCH2, JHH 8 Hz). 13C NMR spectrum, C, ppm:
1
53.94 d (C1, JPC 100 Hz), 127 132 m (C2, C3,
1. Petrov, K.A., Chauzov, V.A., and Erokhina, T.S., Usp.
Khim., 1974, vol. 43, no. 11, p. 2045; Kukhar’, V.P.
and Solodenko, V.A., Usp. Khim., 1987, vol. 56, no. 9,
p. 1504; Kolodyazhnyi, O.I., Usp. Khim., 2006, vol. 75,
no. 3, p. 254.
CH=CH), 113.68 s (C4), 159.00 s (C5), 173.10 s
(C=O), 34.21 s (MeN), 55.00 s (MeO), 22 31 m
(14CH2), 14.09 s (MeC). 31P NMR spectrum, P, ppm:
1
36.25 s. Second isomer. H NMR spectrum, H, ppm:
2
3
6.13 d (C1H, JPH 16 Hz), 6.77 d (C3H, JHH 8 Hz),
7.53 d (C4H, 3JHH 8 Hz), 5.2 5.3 m (CH=CH), 3.01 s
(MeN), 3.68 s (MeO), 1.2 2.0 m (14CH2), 0.82 t
2. Prishchenko, A.A., Livantsov, M.V., Novikova, O.P.,
and Livantsova L.I., Zh. Obshch. Khim., 2007, vol. 77,
no. 9, p. 1574.
(MeCH2, JHH 8 Hz). 13C NMR spectrum, C, ppm:
3
54.05 d (C1, JPC 99 Hz), 127 132 m (C2, C3,
3. Prishchenko, A.A., Livantsov, M.V., Kustrya, D.N.,
Novikova, O.P., Grigor’ev, E.V., and Goncharo-
va, Zh.Yu., Zh. Obshch. Khim., 1997, vol. 67, no. 11,
p. 1914; Prishchenko, A.A., Novikova, O.P., Livan-
tsov, M.V., Kustrya, D.N., and Grigor’ev, E.V., Zh.
Obshch. Khim., 1998, vol. 68, no. 3, p. 514.
1
CH=CH), 113.97 s (C4), 159.35 s (C5), 173.55 s
(C=O), 34.79 s (MeN), 55.00 s (MeO), 22 31 m
(14CH2), 14.09 s (MeC). 31P NMR spectrum, P, ppm:
33.55 s. Found, %: C 67.82; H 8.74. C38H59N2O6P.
Calculated, %: C 68.03; H 8.86.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 2 2008