Synthesis of mono- and bisorganophosphorus substituted amides of unsaturated carboxylic acids with PCHNC(O) and antioxidant fragments

Article abstract of DOI:10.1002/hc.20748

The convenient methods for the synthesis of new mono- and bisorganophosphorus substituted amides of unsaturated carboxylic acids with PCHNC(O) and antioxidant fragments, starting from Arbuzov reaction of the highly reactive adducts of corresponding imines

Full text of DOI:10.1002/hc.20748

Heteroatom Chemistry
Volume 23, Number 1, 2012
Synthesis of Mono- and
Bisorganophosphorus Substituted Amides of
Unsaturated Carboxylic Acids with PCHNC(O)
and Antioxidant Fragments
Andrey A. Prishchenko, Mikhail V. Livantsov, Olga P. Novikova,
Ludmila I. Livantsova, and Valery S. Petrosyan
Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow,
119991 Russia
Received 25 April 2011; revised 15 June 2011
bisorganophosphorus compounds including ionol
ABSTRACT: The convenient methods for the syn-
fragments [6], which were used by us for preparation
thesis of new mono- and bisorganophosphorus sub-
of stable phenoxyl radicals [7] and were possessed of
stituted amides of unsaturated carboxylic acids with
antioxidative activity [8]. In this work, we propose
PCHNC(O) and antioxidant fragments, starting from
the unique way for the synthesis of new mono-
Arbuzov reaction of the highly reactive adducts of
and bisorganophosphorus substituted amides of
corresponding imines and acyl chlorides with
unsaturated carboxylic acids with PCHNC(O)
trimethylsilyl phosphites are proposed. Some proper-
and antioxidant fragments (cf. [9,10]), which was
ties of the new synthesized mono- and bisorganophos-
based on available imines and the corresponding
ꢀ
C
phorus substituted amides are presented.
2011 Wi-
acyl chlorides [11], and trimethylsilyl phosphites
[12].
ley Periodicals, Inc. Heteroatom Chem 23:27–31, 2012;
View this article online at wileyonlinelibrary.com. DOI
10.1002/hc.20748
RESULTS AND DISCUSSION
INTRODUCTION
Note that the substituted N-chloromethylamines
(amides) are widely used by us for preparing vari-
ous functionalized aminomethyl organophosphorus
compounds [13,14]. In the present study we showed
that adducts of imines with unsaturated acyl chlo-
ride A are convenient aminomethylating synthons
for preparing a series of organophosphorus substi-
tuted amides 1–5. Hence, adducts A, which are eas-
ily formed from anisal(methyl)amine and crotonoyl,
cinnamoyl, sorbinoyl, and oleoyl chlorides in methy-
lene chloride (cf. [9]), react with trimethylsilyl phos-
phites by the Arbuzov reaction scheme to give
the corresponding amides 1–5 with high yields
(Eq. (1)).
Functionalized
organophosphorus
substituted
amides of carboxylic acids are of great interest as
effective ligands and promising biological active
compounds of different action [1–5]. Also recently,
we have proposed the convenient methods for
the synthesis of new functionalized mono- and
Correspondence to: Andrey A. Prishchenko; e-mail:
aprishchenko@yandex.ru.
Contract grant sponsor: Russian Foundation for Basic Re-
search.
Contract grant number: 11-03-00402.
2011 Wiley Periodicals, Inc.
c
ꢀ
27

28 Prishchenko et al.
Me
RC(O)Cl
ArCH=NMe
ClCH(Ar)NC(O)R
A
Me
Me
(EtO)2POSiMe3
(Me3SiO)3P
- Me3SiCl
(EtO)2PCH(Ar)NC(O)R
CH(Ar)NC(O)R
(Me3SiO)2P
A
- Me3SiCl
O
O
5
1-4
(CH2)7
C=C
(CH2)7Me
(4).
Ar = 4-MeOC6H4; R = CH=CHMe (1), CH=CHPh (2,5), (CH=CH)2Me (3),
H
H
(1)
Treatment of phosphonate 5 with a dilute solu-
tion of sodium methylate in methanol gives water-
The obtained compounds wth chelating properties
1–14 include carbonyl and phosphoryl groups along
with the unsaturated fragments, pyridine, and 2,6-
di-tert-butylphenol moieties. Therefore, they are of
interest as effective polydentate ligands and also
as promising antioxidants with the multifunctional
mode of action.
soluble disodium salt 6 as hygroscopic crystals (Eq.
(2)), which decomposed on heating above 100–120◦C
without a definite melting point.
Me
2 MeONa
- 2 Me3SiOMe
5
(NaO)2PCH(Ar)NC(O)CH=CHPh
O
The structures of amides 1–14 were confirmed
by the 1H, 13C, 31P NMR spectra, which show charac-
teristic signals of the PC1H(C2)N(C3)C4(O) fragments
and signals of substituted unsaturated and aromatic
fragments (see Table 1). The 1H and13C NMR signals
of unsaturated and aromatic fragments of these
compounds overlap partially or completely. Com-
pounds 1–14 consist of two stereoisomers whose
contents were determined by 1H and 31P NMR
spectroscopy. The contents of the second isomers of
compounds 9,10,12,13 are very low; therefore, here
6
Ar = 4-MeOC6H4.
(2)
Similarly, the easily available iso- and tereph-
taloyl chlorides [11] add readily to different imines
in methylene chloride to give intermediates B,
which react smoothly with diethyl trimethylsilyl
phosphite excess under mild conditions, producing
bisorganophosphorus substituted bisamides in high
yields (Eq. (3)).
2 ArCH=NR
2 (EtO)2POSiMe3
ClCH(Ar)N(R)C(O)
ClC(O)
- 2 Me3SiCl
C(O)N(R)CH(Ar)Cl
C(O)Cl
B
C(O)N(R)CH(Ar)P(OEt)2
O
(EtO)2PCH(Ar)N(R)C(O)
O
7-10
(EtO)2PCH(Ar)N(R)C(O)
O
C(O)N(R)CH(Ar)P(OEt)2
O
or
11-14
Bu-t
OH (9,10,13,14); R = Me (7,11),
Bu-t
Ar = 4-MeOC6H4 (7,8,11,12),
(8,10,12,14), Ph (9,13).
N
(3)
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Mono- and Bisorganophosphorus Substituted Amides of Carboxylic Acids 29
b
s
P
Os
Ar
e
e
e
e
C
()C
a
c
c
c
c
c
s
(C
c
c
c
,s
(C
J
s
c
c
c
e
e
e
e
e
e
e
e
e
e
e
e
e
e
(
PC
J
d
(C
PH
J
H
J
Hd
C
()H
%)
(
Rtaio
C)
(
p
M
d
()%
iled
Y
J
.
N
a
b
c
d
e
Heteroatom Chemistry DOI 10.1002/hc

30 Prishchenko et al.
TABLE 2 Elemental Analyses Data of Compounds 1–14
Calcd. (%)
Found (%)
No.
Empirical Formula
Formula Weight
C
H
C
H
1
C17H26NO5P
C22H28NO5P
C19H28NO5P
355.38
417.44
381.41
551.75
505.69
405.30
704.68
830.81
1025.21
1027.19
704.68
830.81
1025.21
1027.19
57.46
63.30
59.83
67.48
57.00
53.34
57.95
60.72
67.95
65.48
57.95
60.72
67.95
65.48
7.38
6.76
7.40
9.86
7.17
4.48
6.58
5.82
7.67
7.46
6.58
5.82
7.67
7.46
57.32
63.12
59.69
67.37
56.89
53.23
57.78
60.59
67.81
65.43
57.69
60.64
67.76
65.30
7.30
6.64
7.26
9.78
7.11
4.41
6.49
5.73
7.54
7.39
6.52
5.74
7.58
7.42
2
3
4
C31H54NO5P
5
C24H36NO5PSi2
C18H18NNa2O5P
C34H46N2O10P2
C42H48N4O10P2
6
7
8
9
C58H78N2O10P2
10
11
12
13
14
C56H76N4O10P2
C34H46N2O10P2
C42H48N4O10P2
C58H78N2O10P2
C56H76N4O10P2
we give for them 31P NMR parameters only. The ele-
mental analysis data of synthesized compounds are
summarized in Table 2.
removed in a vacuum, and the residue was kept in a
vacuum (1 mm Hg) for 1 h to obtain 4.6 g of the salt
6, as yellow hygroscopic crystals.
1,3-Bis{N-methyl-N-[4-anisyl(diethoxyphosphor-
yl)methyl]aminocarbonyl}benzene (7). A solution of
4.06 g of isophtaloyl chloride in 10 mL of methy-
lene chloride was dropwise added to a solution of
6 g of anisal(methyl)amine in 15 mL of methylene
chloride at 0◦C under stirring. After 1 h, this mixture
was added to a solution of 8.5 g diethyl trimethylsi-
lyl phosphite in 10 mL of methylene chloride. The
mixture was stirred for 2 h at 20◦C. The solvent
was removed, and to the residue was added 3 mL
of hexane. This mixture was cooled to –10◦C. The
solvent was decanted, and the precipitated crystals
were kept in a vacuum of 0.5 mm Hg for 1 h, yield-
ing 12.5 g of phosphonate 7. Bisphosphonates 8–14
were obtained analogously.
EXPERIMENTAL
1
The H, 13C, and 31P NMR spectra were registered
on a Bruker Avance-400 spectrometer (400, 100, and
162 MHz, respectively) in CDCl3 (1–5,7,11), CD3OD
(6) or (CD3)2SO (8–10,12–14) against TMS (1H and
13C) and 85% H3PO4 in D2O (31P). All reactions
were performed under dry argon in anhydrous sol-
vents. Starting imines, unsaturated acid chlorides,
and trimethylsilyl phosphites were prepared accord-
ing to the procedures in [11,12], respectively.
O, O−Diethyl [4-anisyl(N-methyl-N-crotonoyla-
mino)methyl]phosphonate (1). A solution of 5.2 g of
crotonoyl chloride in 10 mL of methylene chloride
was added dropwise with stirring at 0◦C to a solution
of 9 g of anisal(methyl)amine in 20 mL of methy-
lene chloride. After 1 h, a solution of 14 g of diethyl
trimethylsilyl phosphite in 15 mL of methylene chlo-
ride was added. The solvent was distilled off, 25 mL
of hexane was added to the residue, and the mixture
was cooled to –10◦C. The precipitated thick oil was
removed from solvent and kept in a vacuum (0.5 mm
Hg) for 1 h. Phosphonate 1, 16.5 g, was obtained.
REFERENCES
[1] Kukhar, V.P.; Hudson, H.R. Aminophosphonic and
Aminophosphinic Acids. Chemistry and Biological
Activity; Wiley: New York, 2000.
[2] Kolodiazhnyi, O.I. Usp Khim 2006, 75, 254–282 (in
Russian).
[3] Galezowska, J.; Szyrwiel, L.; Mlynarz, P.; Sliwinska,
S.; Kafarski, P.; Kozlowski, H. Polyhedron 2007, 26,
4287–4293.
[4] Mlynarz, P.; Olbert-Majkut, A.; Sliwinska, S.;
Schroeder, G.; Bankowski, B.; Kafarski, P. J Mol
Struct 2008, 873, 173–180.
[5] Lewkowski, J.; Dziegielewski, M. Heteroat Chem
2009, 20, 431–435.
[6] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Milaeva, E. R. Heteroat Chem 2008,
19, 490–494.
Amides 2–5 Were Prepared Similarly
Disodium 4-anisyl(N-methyl-N-cinnamoyl)methyl-
phosphonate (6). A solution of 6 g of phosphonate
5 in 10 mL of diethyl ether was added with stirring
and cooling at 10◦C to a solution of 1.3 g of sodium
methylate in 30 mL of methanol. The resulting
mixture was heated to the boil, the solvent was
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Mono- and Bisorganophosphorus Substituted Amides of Carboxylic Acids 31
[7] Tyurin, V.Yu.; Gracheva, Yu. A.; Milaeva, E. R.; Pr-
[10] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Milaeva, E. R. Heteroat Chem 2009,
20, 70–80.
ishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Maryashkin, A. V.; Bubnov, M. P.;
Kozhanov, K. A.; Cherkasov, V.K. Russ Chem Bull
2007, 744–750.
[11] Hilgetag, G.; Martini, A. Weygand-Hilgetag.
Organisch-Chemische
Experimentierkunst;
[8] Berberova, N. T.; Osipova, V. P.; Koljada, M. N.;
Antonova, N. A.; Zefirov, N. S.; Milaeva, E. R.; Fil-
imonova, S. I., Gracheva, Yu. A.; Prishchenko, A. A.;
Livantsov, M. V.; Livantsova, L. I.; Novikova, O. P.
Patent RU 2405032 C 1, Int. Cl. C11B 5/00. Russian
Patent Bull 2010, 33 (in Russian).
[9] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Milaeva, E. R. Heteroat Chem 2008,
19, 733–737.
Khimiya: Moscow, 1968 (in Russian).
[12] Wozniak, L.; Chojnowski, J. Tetrahedron 1989, 45,
2465–2524.
[13] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O.P.;
Livantsova, L.I.; Petrosyan, V. S. Heteroat Chem
2008, 19, 345–351.
[14] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O.
P.; Livantsova, L. I.; Petrosyan, V. S. Heteroat Chem
2008, 19, 500–505.
Heteroatom Chemistry DOI 10.1002/hc