Synthesis of new amidophosphates containing an adamantyl fragment under microwave irradiation

Article abstract of DOI:10.1134/S1070428010020028

The reaction of amines containing an adamantly fragment with diethyl phosphite in tetrachloromethane in the presence of triethylamine was studied under the microwave irradiation.

Full text of DOI:10.1134/S1070428010020028

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 162−165. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © L.I. Minaeva, L.S. Patrikeeva, B.S. Orlinson, I.A. Novikov, M.M. Kabachnik, I.P. Beletskaya, 2009, published in Zhurnal
Organicheskoi Khimii, 2010, Vol. 46, No. 2, pp. 172−174.
Synthesis of NewAmidophosphates Containing anAdamantyl
Fragment under Microwave Irradiation
L. I. Minaevaa, L. S. Patrikeevaa, B. S. Orlinsonb, I. A. Novikovb,
M. M. Kabachnika, and I. P. Beletskayaa
aLomonosov Moscow State University, Moscow, Russia
e-mail: mariamk@mail.ru
bVolgograd State Technical University, Volgograd, Rissia
Received April 9, 2009
Abstract—The reaction of amines containing an adamantly fragment with diethyl phosphite in tetrachloromethane
in the presence of triethylamine was studied under the microwave irradiation.
DOI: 10.1134/S1070428010020028
The synthesis of functionally substituted amido-
phosphates is an urgent task of the modern organo-
phosphorus chemistry, first of all due to the practical
application of these compounds in the chemistry, biology,
and medicine. The amidophosphates are known to be
efficient inhibitors of various enzymes [1–4], they are
used in the treatment of virus diseases [5], but the most
practically interesting is theAIDS treatment [6] employing
this class of organophosphorus compounds. Sometimes
the amidophosphates are used as ionic polymerization
initiators [7], in other events they are successfully applied
as catalysts in asymmetric synthesis [8].
only published example of the use of Todd–Atherton
reaction in the synthesis of an amidophosphate with an
adamantly fragment was the preparation of diethyl
1-adamantylamidophosphate [20]. The yield of the product
was 58%.
The application of microwave irradiation for
accelerating some organic processes is widely known
[21], in particular, we have successfully used it in the
synthesis of α-amino- and α-hydroxyalkylphosphonates
[22].
Aiming at the optimization of the synthesis conditions
of amidophosphate and at the preparation of previously
unknown adamantly-containing organophosphorus
compounds we studied the reaction of the corresponding
amines with diethyl phosphite in tetrachloromethane in
the presence of triethylamine under the microwave
irradiation. Previous to our work the Todd–Atherton
reaction never was carried out under the microwave
irradiation.
Although versatile amidophosphates are well studied
[9], the synthesis of new types of these compounds still
remains an urgent task. Organophosphorus compounds
with an adamantyl fragment in their structure also are
objects of thorough investigation for they exhibit a high
biological action against osteoporosis [10], and also
antibacterial effect [11].
The application of the microwave assistance made it
possible to obtain fast (in several minutes) and in high
yields adamantly-containing amidophosphate and to
decrease considerably the formation of the reaction side
products.
These compounds are commonly obtained either by
the reaction of appropriate amines with phosphoric acid
ester chlorides at heating [12–18], or by the Todd–
Atherton reaction [19, 20]. In the first case the yields of
the reaction products do not exceed 60%; in the second
event the reaction proceeds either at the room
temperature or at heating (from 2 to 17 h depending on
the structure of the initial compounds), and it is
complicated by a number of side processes, in particular,
by the formation of pyrophosphates and phosphates. The
The reaction of amines Ia–If with diethyl phosphite in
tetrachloromethane was carried out under the microwave
irradiation in the presence of an equimolar quantity of
triethylamine. According to the 31P NMR spectra the
reaction of amines Ia–If with diethyl phosphite under these
162

SYNTHESIS OF NEW AMIDOPHOSPHATES CONTAINING AN ADAMANTYL FRAGMENT
163
conditions proceeded virtually quantitatively.
General procedure. Into an open flat-bottom flask of
25 ml capacity was charged 0.01 mol of amine Ia–If, 10
ml of tetrachloromethane, then 0.01 mol of O,O'-diethyl
phosphite, and 0.01 mol of triethylamine. The reaction
was carried out under the microwave irradiation (102 W,
115°C) for 7–20 min. The separated precipitate of
triethylamine hydrochloride was filtered off, the
amidophosphates were isolated by column chromato-
graphy on silica gel (eluent chloroform–hexane, 1 : 1).
RNH2
(EtO) P(O)H
+
2
CCl4, Et3N, MW
_CHCl3,
RHN
P(O)(OEt)2
_Et3N HCl
.
R = AdCH2 (a), AdCH(Et) (b), AdCH(Ph) (c),
Ad(CH2CH2)2 (d),AdOCH2CH2 (e),AdCH2CH(CH3) (f).
Diethyl N-[(1-adamantyl)methyl]amidophosphate
(IIa). Reaction time 14 min. Yield 2.8 g (93%). Yellow
oily substance. 1H NMR spectrum (CDCl3), δ, ppm: 0.88
d (6H, CCH2CH, 3J 6.9 Hz), 1.33 t (3H, OCH2CH3,
3J 7.1 Hz), 1.42 t (3H, OCH2CH3, 3J 7.1 Hz), 1.64 m
(6H, CHCH2CH), 1.99 m (3H, CH2CHCH2), 3.12 s (2H,
CCH2NH), 4.06 m (4H, OCH2CH3). 13C NMR spectrum
(CDCl3), δ, ppm: 16.25 d (OCH2CH3), 28.22 s
(CH2CHCH2), 36.98 s (CHCH2CH), 39.96 s (CCH2CH),
53.51 s (CCH2NH), 62.23 s (OCH2CH3). 31P NMR
spectrum: δ 10.1 ppm. Found, %: C 59.93; H 9.41;
N 4.25. C15H38NO3P. Calculated, %: C 59.78; H 9.36;
N 4.65.
In reaction with amine Id containing two equivalent
amino groups a double exess was taken of the diethyl
phosphite and triethylamine, and this resulted in the
formation in a high yield of bis(amidophosphate) IId. The
structure and composition of compound IId were
1
confirmed by the data of H, 13C NMR spectra and
elemental analysis. Bringing into this reaction of equimolar
amounts of amine Id, diethyl phosphite, and triethylamine
aso resilted in the formation only of amidophosphate IId.
No phosphorylation at a single amino group was found.
The process carried out at room temperature is
considerably slower. The reaction of amine Ia with diethyl
phosphite in the presence of triethylamine at room
temperature took 1.5 h, and the corresponding amido-
phosphate IIa formed in 62% yield.
Diethyl N-[1-(1-adamantyl)propyl]amidophos-
phate (IIb). Reaction time 18 min. Yield 2.8 g (85%),
mp 97–99ºC. 1H NMR spectrum (CDCl3), δ, ppm: 1.02 t
(3H, NHCHCH2CH3, 3J 6.9 Hz), 1.10 d (6H, CCH2CH,
3J 6.9 Hz), 1.32 t (6H, OCH2CH3, 3J 7.1 Hz), 1.63 m
(6H, CHCH2CH), 1.99 m (3H, CH2CHCH2), 2.09 m (2H,
NHCHCH2CH3), 2.58 s (1H, CCHNH), 4.09 m (4H,
OCH2CH3). 13C NMR spectrum (CDCl3), δ, ppm:
11.95 s (CCHCH2CH3), 16.27 d (OCH2CH3), 23.67 s
(CCHCH2CH3), 28.47 s (CH2CHCH2), 37.16 s
(CHCH2CH), 38.69 s (CCH2CH), 62.39 s (OCH2CH3),
63.32 s (CCHCH2CH3). 31P NMR spectrum: δ 9.1 ppm.
Found, %: C 61.89; H 9.77; N 4.03. C17H32NO3P.
Calculated, %: C 61.98; H 9.79; N 4.25.
Hence we demonstrated that the reaction of the
adamantyl-containing amines with diethyl phosphite in
tetrachloromethane in the presence of triethylamine under
the microwave irradiation provided a possibility to obtain
quickly and in high yields previously unknown
amidophosphates with adamantyl substituents.
EXPERIMENTAL
1H, 13C, and 31P NMR spectra were registered on
a spectrometer Bruker Avance-400 (operating
frequencies 400, 100.6, and 161.9 MHz respectively).
As internal reference served the chloroform signals
(δH 7.28, δC 77.10 ppm). the melting points were
measured on an Electrothermal 9100 instrument. The
reaction progress was monitored and the purity of the
chemical compounds was checked by TLC (Silufol UV-
254). For preparative column chromatography silica gel
Merck (40/60) was used.
Diethyl N-[α-(1-adamantyl)benzyl]amidophos-
phate (IIc). Reaction time 10 min. Yield 3.2 g (84%),
mp 108–110ºC. H NMR spectrum (CDCl3), δ, ppm:
1
1.29 t (6H, OCH2CH3,3J 7.0 Hz), 1.38 m (6H, CCH2CH),
1.67 m (6H, CHCH2CH), 1.98 m (3H, CH2CHCH2),
2.34 s (1H, CCHNH), 4.00 m (4H, OCH2CH3), 7.15–
7.31 (5H, C6H5). 13C NMR spectrum (CDCl3), δ, ppm:
16.18 d (OCH2CH3), 28.30 s (CH2CHCH2), 36.80 s
(CHCH2CH), 38.79 s (CCH2CH), 62.26 s (OCH2CH3),
65.60 s [CCH(Ph)NH], 126.78 s, 127.41 s, 128.35 s
(C6H5). 31P NMR spectrum: δ 8.5 ppm. Found, %:
C 66.53; H 8.75; N 3.91. C21H32NO3P. Calculated, %:
Synthesis of amidophosphates containing an
adamantane fragment under microwave assistance.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

MINAEVA et al.
164
C 66.82; H 8.55; N 3.71.
of the Russian Foundation for Basic Research (grant no.
08-03-00178).
Tetraethyl[adamantane-1,3-diylbis(ethane-2,2'-
diyl)]bisamidophosphate (IId). Reaction time 20 min.
Yield 4.1 g (82%). Oily substance. H NMR spectrum
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