Synthesis of unsaturated carboxylic and amino acids of adamantane series with the use of organophosphorus reagents

Article abstract of DOI:10.1023/A:1015501313852

Sodium derivative of diethyl(3-amino-1-ethoxycarbonylpropane)phosphonic acid was obtained by reaction of triethyl phosphonoacetate with ethylene imine in the presence of sodium hydride. The compound obtained was brought into Horner-Emmons reaction with ca

Full text of DOI:10.1023/A:1015501313852

Russian Journal of Organic Chemistry, Vol. 38, No. 2, 2002, pp. 188 190. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 2, 2002,
pp. 207 209.
Original Russian Text Copyright
2002 by Miryan, Isaev, Yurchenko, Gulyaiko, Voinovskaya, Rassukana, Shchirova.
Synthesis of Unsaturated Carboxylic and Amino Acids
of Adamantane Series with the Use of Organophosphorus
Reagents
N. I. Miryan, S. D. Isaev, A. G. Yurchenko, I. V. Gulyaiko,
T. Yu. Voinovskaya, Yu. V. Rassukana, and N. V. Shchirova
Ukrainian National Technical University, Polytechnical Institute, Kiev, 01056 Ukraine
Received October 18, 2000
Abstract Sodium derivative of diethyl(3-amino-1-ethoxycarbonylpropane)phosphonic acid was obtained by
reaction of triethyl phosphonoacetate with ethylene imine in the presence of sodium hydride. The compound
obtained was brought into Horner Emmons reaction with carbonyl derivatives of adamantane series to
afford the corresponding unsaturated amino acids. From adamantanecarbonyl chlorides and triphenyl-
phosphonium ethoxycarbonylmethylide new phosphorus acylylides that on thermolysis provide ethyl acetyl-
enecarboxylates containing an adamantyl substituent were prepared.
We formerly described [1] a procedure for syn-
thesis of esters of unsaturated carboxylic acids,
adamantane derivatives, by reaction of triethyl
phosphonoacetate with appropriate carbonyl com-
pounds (Horner Emmons reaction).
We expected that at the use in the reaction of
phosphonoacetates substituted in the methylene group
the substituent would be conserved in the reaction
product thus providing a possibility of synthesis of
unsaturated acids with a substituent in the -position
with respect to the carboxy group. It is known that
ylides are capable of reacting with N-substituted
aziridines containing electron-withdrawing substitu-
ents to provide phosphorus ylides with 2-aminoethyl
Scheme.
1070-4280/01/3802-188$27.00 2002 MAIK Nauka/Interperiodica

SYNTHESIS OF UNSATURATED CARBOXYLIC AND AMINO ACIDS
189
group at the ylide carbon [2]. This reaction is not
described in the literature for phosphonoacetates and
unsubstituted aziridine.
thermolysis at 250 260 C in a vacuum of 1 2 mm
Hg, and in 25 30 min they virtually quantitatively
are converted into ethyl acetylenecarboxylates
XVIII XX.
We established that triethyl phosphonoacetate I
reacted with ethylene imine in the diglyme in the
presence of sodium hydride at 100 120 C to afford
sodium derivative of phosphonate II.
We failed to synthesize cage-like derivatives of
acetylene by thermolysis of acylylides of adamantane
series without carboxy group.
The composition and structure of compounds
obtained were confirmed by elemental analyses, IR
1
and H NMR spectra.
EXPERIMENTAL
1H NMR spectra were recorded on spectrometer
Tesla BS-487C (80 MHz) in CDCl3, chemical shifts
were given relative to TMS. IR spectra were measur-
ed on Specord instrument from solutions in CCl4.
Only characteristic absorption bands of stretching
vibrations are listed below. Elemental analyses were
carried out on CHN-Analyzer. The melting point
were measured on Boetius heating block, and the
reported values were corrected.
The phosphonate can be isolated from the sodium
derivative II as individual compound at acidification,
but compound II was used in subsequent reactions
without separation from the reaction mixture. Com-
pound II reacts with carbonyl compounds in the same
way as triethyl phosphonoacetate. As carbonyl com-
pounds we used adamantanone (III), protoadamanta-
none (IV), 1-adamantylacetic aldehyde (V), and cyclo-
hexanone (VI). The reaction proceeds at 100 120 C
in diglyme for 25 30 h and affords ethyl -amino-
butyrates VII X in 25 60% yield (see scheme).
Ethyl -adamantylidene- -aminobutyrate (VII).
To a solution of 1.5 g (6.7 mmol) of triethyl phos-
phonoacetate (I) in 10 ml of anhydrous diglyme was
added at stirring in an argon flow 0.168 g (7 mmol)
of sodium hydride. The mixture was stirred till the
end of hydrogen evolution, then it was charged into
an ampule, and 0.344 g (8 mmol) of ethylene imine
was added. The ampule was sealed and heated to
100 120 C for 5 h. Then it was opened, and 1 g
(6.7 mmol) of adamantanone (III) was added, the
ampule was sealed again and heated to 100 120 C
for 30 h. Afterwards the solvent was distilled off
from the reaction mixture in a vacuum, the residue
was treated with water, the reaction product was
extracted into dichloromethane, the extract was dried
with sodium sulfate, the solvent was distilled off, and
the residue was subjected to vacuum-distillation.
Yield of compound VII 0.8 g (45%), bp 160 C
According to published data [3, 4, 5] ylides
acylated at the ylide carbon atom can be converted
into acetylene by various methods: by successive
treatment with trifluoromethanesulfonic anhydride
and sodium amalgam, or with phosphorus oxychloride
and alkali, or by pyrolysis. We synthesized in high
yield acylylides containing adamantyl radical by treat-
ing with adamantanecarbonyl chlorides triphenyl-
phosphonium ethoxycarbonylmethylide (XI).
1
(3 mm Hg). IR spectrum (cm ): 3400 3500 (NH
primary), 1700 (COOC2H5). 1H NMR spectrum
( , ppm): 3.95 quint (2H, OCH2), 2.55 2.8 m (6H,
CH2CH2NH2), 1.45 2.22 m (14H adamantyl), 1.15 t
(3H, CH3). Found, %: C 72.85, 72.90; H 9.35, 9.57;
N 5.15, 5.25. C16H25NO2. Calculated, %: C 73.00;
H 9.5; N 5.3.
Ethyl -(4-protoadamantylidene)- -amino-
butyrate (VIII) was obtained in a similar way from
1.14 g (7.1 mmol) of 4-protoadamantanone. Yield
0.47 g (25%), bp 75 77 C (1 2 mm Hg). IR spec-
n = 0 (XII, XV, XVIII), 1 (XIII, XVI, XIX),
2 (XIV, XVII, XX).
Ylides obtained are outstanding in their inertness
to hydrolysis, but they relatively readily undergo
1
trum (cm ): 3350 3400 (NH primary), 1700
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 2 2002

190
MIRYAN et al.
(COOC2H5) . 1H NMR spectrum ( , ppm): 4.0 q
(2H, OCH2), 1.1 2.42 m (14H protoadamantyl; 6H,
CH2CH2NH2; 3H, CH3). Found, %: C 72.80, 72.95;
H 9.32, 9.45; N 5.02, 5.15. C16H25NO2. Calculated,
%: C 73.00; H 9.5; N 5.3.
was synthesized similarly to compound XV from
ylide XI and 1.49 g (6.6 mmol) of compound XIV,
yield 2.8 g (79%). 1H NMR spectrum ( , ppm):
(15H, phenyl), 3.90 q (2H, OCH2), 1.52 1.92 m
(15H adamantyl, 4H, CH2CH2), 0. 92 t (3H,
CH3). Found, %: P 5.68, 5.82. C35H39O3P.
Calculated, %: P 5.76.
Ethyl -[2-(1-adamantyl)ethylidene]- -amino-
butyrate (IX) was obtained in a similar way from
1.18 g (6.6 mmol) of 1-adamantylacetaldehyde (V).
Yield 1.16 g (60%), bp 132 134 C (2 mm Hg). IR
Ethyl 3-(1-adamantyl)propynoate (XVIII). In a
round-bottom flask was heated to 250 260 C in a
vacuum 1 g (1.96 mmol) of triphenylphosphonium
[ -(1-adamantanecarbonyl)- -ethoxycarbonyl]methyl-
ide (XV). Thermolysis was accompanied with
sublimation of triphenylphosphine oxide. At 180 C
and 5 mm Hg was distilled the reaction product that
was subsequently twice washed with petroleum ether
to purify from triphenylphosphine oxide. Yield of
oily compound XVIII 0.4 g (88%). IR spectrum
1
spectrum (cm ): 3400 3500 (NH primary), 1710
1
(COOC2H5). H NMR spectrum ( , ppm): 7.07 m
(1H, =CH), 4.0 q.d. (2H, OCH2), 1.43 2.8 m (15H,
adamantyl, 6H, CH2CH2NH2), 1.15 t (3H, CH3).
Found, %: C 74.15, 74.32; H 9.85, 9.80; N 4.75,
4.90. C18H29NO2. Calculated, %: C 74.22; H 9.96;
N4.81.
Ethyl -(cyclohexylidene)- -aminobutyrate (X)
was obtained in a similar way from 0.65 g
(6.6 mmol) of cyclohexanone (VI). Yield 0.84 g
(60%), bp 65 70 C (3 4 mm Hg). IR spectrum
1
(cm ): 2230 (C C), 1700 (COOC2H5). 1H NMR
spectrum ( , ppm): 3.97 q (2H, OCH2), 1.3 1.87 m
(15H, adamantyl), 1.15 t (3H, CH3). Found, %: C
77.34, 77.48; H 8.45, 8.60. C15H20O2. Calculated,
%: C 77.58; H 8.62.
1
(cm ): 3300 3500 (NH primary), 1710 (COOC2H5).
1H NMR spectrum ( , ppm): 3.95 q (2H, OCH2),
1.67 2.25 m (10H, cyclohexyl; 7H, CH2CH2NH2),
1.15 m (3H, CH3). Found, %: C 68.10, 68.36; H
9.70, 9.86; N 6.32, 6.70. C12H21NO2. Calculated,
%: C 68.24; H 9.9; N 6.63.
Ethyl 4-(1-adamantyl)butynoate (XIX) was
obtained in a similar way from 3.45 g (6.6 mmol) of
compound XVI. Yield 1.07 g (66%), bp 165 170 C
1
(7 mm Hg). IR spectrum (cm ): 2200 (C C), 1700
1
(COOC2H5). H NMR spectrum ( , ppm): 3.7 q (2H,
Triphenylphosphonium [ -(1-adamantanecarb-
onyl)- -ethoxycarbonyl]methylide (XV). To a solu-
tion of 3.9 g (12.2 mmol) of triphenylphosphonium
ethoxycarbonylmethylide (XI) in anhydrous benzene
(30 ml) was added a solution of adamantanecarbonyl
chloride (XII) (1.1 g, 5.6 mmol) in 10 ml of
anhydrous benzene. The reaction mixture was stirred
for 10 h at room temperature. The precipitate of
ethoxycarbonylmethyltriphenylphosphonium chloride
was filtered off, the filtrate was evaporated. We
obtained 2.5 g (87%) of compound XV that was
purified by reprecipitation from a mixture benzene
OCH2), 1.3 2.0 m (15H, adamantyl, 2H, CH2),
1.15 t (3H, CH3). Found, %: C 77.90, 78.10; H 8.75,
8.85. C16H22O2. Calculated, %: C 78.04; H 8.94.
Ethyl 5-(1-adamantyl)pentynoate (XX) was
obtained in a similar way from 3.55 g (6.6 mmol) of
compound XVII. Yield 0.41 g (82%), bp 140 C
(3 6 mm Hg). IR spectrum (cm-1): 2230 (C C), 1700
1
(COOC2H5). H NMR spectrum ( , ppm): 3.97 q
(2H, OCH2), 1.3 2.0 m (15H, adamantyl, 4H,
CH2CH2), 1.15 t (3H, CH3). Found, %: C 78.35,
78.52; H 9.05, 9.15. C17H24O2. Calculated, %:
C 78.46; H 9.23.
1
hexane. H NMR spectrum ( , ppm): 7.17 7.6 m
(15H, phenyl), 3.90 q (2H, OCH2), 1.52 1.92 m
(15H, adamantyl), 0.92 t (3H, CH3). Found, %: P
6.15, 6.25. C33H35O3P. Calculated, %: P 6.07.
REFERENCES
1. Miryan, N.I.,
Isaev, S.D.,
Kovaleva, S.A., Pe-
Triphenylphosphonium [ -(1-adamantanylacet-
yl)- -ethoxycarbonyl]methylide (XVI) was synthe-
sized similarly to compound XV from ylide XI and
1.4 g (6.6 mmol) of compound XIII, yield 2.83 g
(82%). 1HNMR spectrum ( , ppm): 7.10 7.6 m (15H,
phenyl), 3.90 q (2H, OCH2), 1.52 1.92 m (15H,
adamantane, 2H, CH2), 0.92 t (3H, CH3). Found, %:
P 5.80, 5.98. C34H37O3P. Calculated, %: P 5.91.
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Yurchenko, A.G., Zh. Org. Khim., 1999, vol. 35,
no. 6, pp. 882 886.
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Triphenylphosphonium { -[3-(1-adamantanyl-
propanoyl)]- -ethoxycarbonyl}methylide (XVII)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 2 2002