Ketones in the catalytic three-component "one-pot" Kabachnik - Fields synthesis of α-amino phosphonates

Article abstract of DOI:10.1007/s11172-006-0400-2

Reactions of carbocyclic, heterocyclic, and steroidal ketones with benzylamine and diethyl phosphite in a catalytic three-component "one-pot" synthesis of α-amino phosphonates were studied. The activities of mono-and binuclear complexes of tetra(tert-butyl)phthalocyanines as catalysts for this process were compared. Springer Science+Business Media, Inc. 2006.

Full text of DOI:10.1007/s11172-006-0400-2

Russian Chemical Bulletin, International Edition, Vol. 55, No. 7, pp. 1209—1214, July, 2006
1209
Ketones in the catalytic threeꢀcomponent "oneꢀpot"
Kabachnik—Fields synthesis of αꢀamino phosphonates
E. D. Matveeva,ꢀ T. A. Podrugina, M. V. Prisyajnoy, and N. S. Zefirov
Department of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119899 Moscow, Russian Federation.
Fax: +7 (495) 939 02 90. Eꢀmail: podrugina@mail.ru; matveeva@org.chem.msu.ru
Reactions of carbocyclic, heterocyclic, and steroidal ketones with benzylamine and diethyl
phosphite in a catalytic threeꢀcomponent "oneꢀpot" synthesis of αꢀamino phosphonates were
studied. The activities of monoꢀ and binuclear complexes of tetra(tertꢀbutyl)phthalocyanines
as catalysts for this process were compared.
Key words: αꢀamino phosphonates, Kabachnik—Fields reaction, phthalocyanines, keꢀ
tones, amines, phosphites, organophosphorus compounds.
αꢀAmino phosphonic acids are phosphorus analogs of
αꢀamino carboxylic acids ("bioisosterism"1). The biologiꢀ
cal activities of αꢀamino phosphonic acids, the occurꢀ
rence of natural phosphonates, and proven reactions of
phosphonates with various enzymes and receptors2—6 moꢀ
tivate researchers to look for new routes to αꢀamino
phosphonates,7—11 many of which still remain not easily
accessible. So far design of compounds of this chemotype
presents a nontrivial problem, especially for sterically hinꢀ
dered compounds with complex carbocyclic fragments.
Previously,12 we have proposed a new catalytic threeꢀ
component "oneꢀpot" version of the Kabachnik—Fields
synthesis of αꢀamino phosphonates with metal tetra(tertꢀ
butyl)phthalocyanine complexes tPcM as catalysts.
the synthesis of earlier inaccessible αꢀamino phosphonates
from various carbocyclic and heterocyclic ketones.
We carried out a model reaction of indanꢀ1ꢀone (1)
with benzylamine and diethyl phosphite (Scheme 1) to
compare the catalytic activities of tetra(tertꢀbutyl)phthaloꢀ
cyanine (tPcH2) and some of its metal complexes under
identical conditions.
Scheme 1
The dependence of the yield of αꢀamino phosphonate
2 on the catalyst nature is given in Table 1.
In reactions catalyzed by terbium diphthalocyanines,
in which access to the metal ion is prevented by the
phthalocyanine rings, the yield of amino phosphonate 2
was moderate and comparable with the yields attained
with free tPcH2 (see Table 1). The yield of amino
phosphonate 2 gradually increases when the central atom
of the complex exhibit more pronounced metallic properꢀ
ties. The highest yield of the target product was obtained
with tPcAlCl. In addition, we illustrated with amino phosꢀ
M = H2, AlCl, CrCl, CoII, NiII, Tb
The use of phthalocyanine catalysis has allowed this
reaction to be extended to ketones, including sterically
hindered ones.12—15 Here we employed this method for
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1164—1169, July, 2006.
1066ꢀ5285/06/5507ꢀ1209 © 2006 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Matveeva et al.
Table 1. Catalyst effect on the yield of αꢀamino phosphonate 2
(30%) of the corresponding amino phosphonate 20 was
reached only with a threefold excess of benzylamine and
diethyl phosphite and microwave (MW) activation, which
provided substantial reduction in the reaction time as
well. In the absence of the catalyst, amino phosphonate
20 did not form even with MW activation.
Catalytic reactions of βꢀdicarbonyl acetylacetone (12)
and ethyl 2ꢀoxocyclopentaneꢀ1ꢀcarboxylate (13) gave
enamines 25, 26 that did not react with diethyl phosphite
(Scheme 2).9
Tetra(tertꢀbutyl)phthalocyanine
Yield of 2 (%)
complex
tPcAlCl
tPcCrCl
tPcCoII
95
85
50
45
45
30
30
0
tPcCoIII
tPcNi
I
tPcH2
(tPc)2Tb (green or blue)
Without a catalyst
Scheme 2
t
phonate 2 that PcAlCl can be reused in a catalytic cycle
without lowering the yield of the target product.
This catalytic threeꢀcomponent process was employed
for the synthesis of αꢀamino phosphonates 2 and 15—24
from various monoꢀ and dicarbonyl compounds 1
and 3—14. A summary of these experiments is given in
Table 2.
R1 = R3 = Me, R2 = Н (12, 25);
In many cases, this approach afforded amino phosꢀ
phonates in high yields. However, the yields of the target
products were lower for sterically hindered starting keꢀ
tones. For instance, with camphor 8a, the highest yield
R1+R2 = (CH2)3, R3 = OEt (13, 26)
In contrast, αꢀdiketone 14 reacted with two equivaꢀ
lents of benzylamine and diethyl phosphite to form
the corresponding bis(αꢀamino phosphonate) 24 and
2ꢀbenzyliminoꢀ1,2ꢀdiphenylethyl diethyl phosphate
(Scheme 3).
Table 2. Yields of αꢀamino phosphonates in tPcAlClꢀcataꢀ
lyzed reactions of different ketones with PhCH2NH2 and
(EtO)2P(O)H
Scheme 3
Ketone
Reaction conditions
Product
(yield (%))
Solvent
τ/h
na
Indanꢀ1ꢀone (1)
Fluorenone (3)
Anthrone (4)
CH2Cl2
CH2Cl2
CH2Cl2
18
72
72
72
24
12
—
—
—
2
3
—
2 (95)b
15 (40)c
16 (20)
17 (75)
18 (50)
19 (60)
9,10ꢀAnthraquinone (5) CH2Cl2
1,4ꢀBenzoquinone (6)
Cyclopropyl methyl
ketone (7)
Camphor (8a)
(1R)ꢀ(+)ꢀCamphor (8b) PriOHe
CH2Cl2
CH2Cl2
EtOHd
4
24•7
18
3
3
1.5
2
2
2
20 (30)
20 (25)
21 (99)
22 (90)
23 (40)
NꢀBocꢀPiperidone (9)
Isatin (10)
CH2Cl2
CH2Cl2
CH2Cl2 24•7
CH2Cl2
CH2Cl2
48
t
i. 2 PhCH2NH2, 2 (EtO)2P(O)H, PcAlCl.
Pregnane (11)
Acetylacetone (12)
Ethyl 2ꢀoxocycloꢀ
pentaneꢀ1ꢀcarbꢀ
oxylate (13)
f
48
48
—
—
Reactions with indanꢀ1ꢀone (1), fluorenone (3), and
anthrone (4) gave, along with the target αꢀamino phosꢀ
phonates 2, 15, and 16, αꢀhydroxy phosphonates and
phosphates as products of their rearrangement in low yields
(5—15%) (Scheme 4).
The proposed method was used to obtain αꢀamino
phosphonates from quinones. It was found that
9,10ꢀanthraquinone (5) reacts with a double excess of
benzylamine and diethyl phosphite to give bis(αꢀamino
phosphonate) 17 in 75% yield. Under analogous condiꢀ
tions, 1,4ꢀbenzoquinone (6) produced the corresponding
f
2
Benzil (14)
CH2Cl2
48
2.5
24 (30)
a With an excess of the reagents per mole of the ketone.
b The yield was 85% with the use of PcCrCl.
t
c The yield was 5% with the use of PcCrCl.
t
d MW activation.
e 80 °C.
f Under these reaction conditions, ketones 12 and 13 form the
corresponding enamines.

Oneꢀpot synthesis of αꢀamino phosphonates
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
1211
Scheme 4
Scheme 6
t
i. PhCH2NH2, (EtO)2P(O)H, PcAlCl.
bis(αꢀamino phosphonate) 18 in ~30% yield. Its yield was
increased to 50% by employing a triple excess of the reꢀ
agents; in this case, diethyl 4ꢀhydroxyphenyl phosphate
formed as a byꢀproduct in 50% yield (Scheme 5).
Scheme 5
t
i. (EtO)2P(O)H, PhCH2NH2, PcAlCl.
Scheme 7
t
i. PhCH2NH2, (EtO)2P(O)H, PcAlCl.
Under standard conditions, heterocyclic ketones such
as NꢀBocꢀpiperidone (9) and isatin (10) gave the correꢀ
sponding αꢀamino phosphonates 21 and 22 in high
yields. Small amount of αꢀhydroxy phosphonate (diethyl
3ꢀhydroxyꢀ2ꢀoxoꢀ2,3ꢀdihydroꢀ1Hꢀindolꢀ3ꢀyl phosphonꢀ
ate) was detected in the reaction with isatin (Scheme 6).
The title method allows access to amino phosphonates
based on complex and polyfunctional ketones. For inꢀ
stance, the hormone pregnane 11 reacted with two equivaꢀ
lents of benzylamine and diethyl phosphite to give
bis(αꢀamino phosphonate) 23 in 40% yield (Scheme 7).
Special experiments showed that these reactions do
not follow the desired pathway in the absence of phthaloꢀ
cyanine catalysts. In addition, byꢀproducts (αꢀhydroxy
phosphonates) in phthalocyanineꢀcatalyzed reactions with
benzylamine did not yield the corresponding αꢀamino
phosphonates.
t
i. 2 PhCH2NH2, 2 (EtO)2P(O)H, PcAlCl.
The 31P NMR spectra of all the αꢀbenzylamino
phosphonates obtained show signals at δ 20.5—29.5 relatꢀ
ing to the dialkyl phosphonate group.16 Their IR spectra
contain absorption bands at 1240—1250 (P=O),
3200—3400 (NH), and 1180 cm–1 (hydrogenꢀbonded
P=O). It should be noted that the absorption intensities
and frequencies of the P=O group and the associated
group remained unchanged upon the dilution of solutions
The structures of αꢀbenzylamino phosphonates 2 and
15—24, αꢀhydroxy phosphonates, and phosphates were
confirmed by IR, NMR (1H, 13C, and 31P), and mass
spectra and elemental analysis data.

1212
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Matveeva et al.
was 95%, Rf 0.24 (CH2Cl2—EtOH, 35 : 1). Found (%): C, 66.62;
H, 7.08; N, 3.81. C20H26NO3P. Calculated (%): C, 66.84;
H, 7.29; N, 3.90. 1H NMR, δ: 1.28, 1.32 (both t, 3 H each,
2 Me, J = 7.0 Hz); 2.34, 2.66, 3.02 (all m, 2 H each, CH2,ring);
3.10 (br.m, 1 H, NH); 3.55 (HA), 3.73 (HB, AB system, 2 H,
CH2Ph, 2JH,H = 12.7 Hz); 3.85, 4.04, 4.12 (all m, 4 H, 2 OCH2);
7.26, 7.50 (both m, 9 H, arom.). 31P NMR, δ: 27.82. 13C NMR,
of the amino phosphonates in CCl4, which suggests intraꢀ
molecular hydrogen bonding.
The 1H NMR spectra of αꢀamino phosphonates show
signals for chemically nonequivalent ethoxy groups. The
signals for the methyl protons appear at δ 1.13 and 1.27
(both t, 1 : 1); the complex multiplets for the methylene
protons of the ethoxy groups appear at δ 3.80—4.50.
A broad singlet at δ 2.10—3.10 corresponds to the amino
group. Signals for the diastereotopic methylene protons
of the benzyl group appear as two doublets or AB system
at δ 3.50—3.80 (2J = 12.7—13.4 Hz).
3
δ: 16.48, 16.59 (both d, Me, JC,P = 6.1 Hz); 30.65, 32.12
(CH2,ring); 46.93 (d, CH2Ph, J = 12.3 Hz); 59.68 (d, C(1)ring
,
1JC,P = 154.1 Hz); 62.74, 63.34 (both d, OCH2, 2JC,P = 7.7 Hz);
124.5, 125.69, 126.55, 126.93, 128.24, 128.36, 128.45, 140.66,
145.04 (Carom). IR, ν/cm–1: 1245 (P=O); 3330, 3480 (NH).
Diethyl 1ꢀhydroxyꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀylphosphonate,
a minor product (5%) in the synthesis of compound 2, Rf 0.22
(CH2Cl2—EtOH, 35 : 1). Found (%): C, 57.23; H, 7.11.
The 13C NMR spectra of αꢀamino phosphonates show
signals at δ 55—60 (1JC,P = 144—154 Hz) for the quaterꢀ
nary C atom at the P atom. Signals for the nonꢀisochroꢀ
nous ethoxy groups appear as two, not always resolved
C
13H19O4P. Calculated (%): C, 57.78; H, 7.04. 1H NMR, δ:
1.30 (t, 6 H, 2 Me, J = 7.0 Hz); 2.21, 2.80, 3.02 (all m, 2 H each,
CH2,ring); 3.60 (br.m, 1 H, OH); 4.04, 4.14 (both m, 4 H,
2 OCH2); 7.28, 7.33, 7.59 (all m, 9 H, arom.). 31P NMR, δ:
24.91. IR, ν/cm–1: 1230 (P=O); 3300 (OH).
Recycling of the catalyst recovered in 95% yield by chromaꢀ
tography of the reaction mixture. Benzylamine (2 mmol), anꢀ
hydrous MgSO4 (2 mmol), and the recovered phthalocyanine
catalyst (0.19 mmol) were added to a solution of indanꢀ1ꢀone
(2 mmol) in CH2Cl2 (3 mL). The reaction mixture was stirred
for 3 h, diethyl phosphite (2.4 mmol) was added, and stirring
was continued for an additional 15 h. Subsequent workup was
done according to the general procedure. The yield of αꢀamino
phosphonate 2 was 93—95%.
3
doublets at δ 16 (CH3, JP,C = 6.3—6.4 Hz) and two
doublets at δ 62—63 (OCH2, 2JP,C = 7—8 Hz). The signal
for the CH2Ph group appears as a not always resolved
doublet at δ 50—51 (J = 12—18 Hz). The other signals in
1
the H and 13C NMR spectra of αꢀamino phosphonates
are consistent with the carbon framework structures of the
starting ketones.
Experimental
1
H, 13C, and 31P NMR spectra were recorded on a Bruker
Avance 400 instrument (400.13, 100.61, and 161.98 MHz, reꢀ
spectively) in CDCl3 with Me4Si (1H and 13C) and 85% H3PO4
(
Diethyl 9ꢀbenzylaminoꢀ9Hꢀfluorenꢀ9ꢀylphosphonate (15) was
obtained from fluorenone 3. The yield was 40%, Rf 0.26
(CH2Cl2—EtOH, 35 : 1). 1H NMR, δ: 1.11, 1.27 (both t, 6 H,
2 Me, J = 7.0 Hz); 2.35 (br.m, 1 H, NH); 3.55 (HA), 3.78 (HB,
31P) as the internal standards.
IR spectra were recorded on a URꢀ20 instrument in CCl4.
Elemental analysis was carried out on a VarioꢀII CHN anaꢀ
2
AB system, 2 H, CH2Ph, JH,H = 13.4 Hz); 3.85, 3.94, 4.06
lyzer and by the Korshun—Klimova pyrolysis.
(all m, 4 H, OCH2); 7.18, 7.27, 7.42, 7.73, 7.80 (all m, 13 H,
Mass spectra (MALDI) were recorded on an Autoflex II
instrument (Bruker Daltonics) and an Agilent LC/MSD 1100 SL
instrument with electrospray ionization at atmospheric pressure
(APꢀESI) in the mode of positive ion detection (an ion trap as a
mass analyzer). Recording conditions: temperature of the drying
gas (nitrogen) 300 °C, flow rate 12 L min–1, power supply voltꢀ
age 5000 V, capillary outlet voltage 150 V, methanol as a solvent.
The course of the reactions was monitored and the purity of
chromatographically separated products was checked by TLC
on Silufol plates.
arom.). 31P NMR, δ: 23.09. 13C NMR, δ: 16.08, 16.28 (both d,
3
Me, JC,P = 6.3 Hz); 51.03 (d, CH2Ph, J = 18.8 Hz); 59.41 (d,
C(1)ring, 1JC,P = 154.2 Hz); 62.60, 62.80 (both d, OCH2, 2JC,P
=
7.9 Hz); 126.94, 127.74, 128.16, 128.19, 128.30, 128.51, 136.53,
139.16 (Carom). IR, ν/cm–1: 1250 (P=O); 3300, 3470 (NH).
MS, m/z: 408 [M]+.
Diethyl 9ꢀhydroxyꢀ9Hꢀfluorenꢀ9ꢀylphosphonate, a minor
product (10%) in the synthesis of compound 15, Rf 0.22
(CH2Cl2—EtOH, 35 : 1). 1H NMR, δ: 1.07 (t, 6 H, 2 Me, J =
7.0 Hz); 3.65 (br.m, H, OH); 3.85, 3.92 (both m, 4 H, OCH2);
7.31, 7.39 (both t, 2 H each, arom., J = 7.3 Hz); 7.64, 7.90
(both d, 2 H each, arom., J = 7.3 Hz). 31P NMR, δ: 21.06.
Synthesis of αꢀamino phosphonates 2 and 15—24 (general
procedure). Benzylamine (2 mmol), anhydrous MgSO4 (2 mmol),
t
3
and PcAlCl (0.2 mmol) were added to a solution of a carbonyl
13C NMR, δ: 16.13 (d, Me, JC,P = 4.7 Hz); 63.70 (d, OCH2,
compound (2 mmol) in an appropriate solvent (3 mL). The
reaction mixture was stirred with a magnetic stirring bar for
3—4 h and then diethyl phosphite (2.4 mmol) was added. The
course of the reaction was monitored by TLC (the reaction
times are specified in Table 2).
2JC,P = 6.3 Hz); 80.58 (d, C(1)ring 1JC,P = 162.0 Hz); 119.87,
,
126.15, 127.66, 129.52, 140.68, 143.18 (Carom). IR, ν/cm–1
:
1250 (P=O). MS, m/z: 318 [M]+; 180 [M – P(O)(OEt)2]+;
152 [M – CHOP(O)(OEt)2]+; 105 [C6H4CHO]; 76 [C6H4];
45 [OEt].
Magnesium sulfate was filtered off and washed with
CH2Cl2—MeOH (10 : 1, 3×2 mL). The filtrate was concenꢀ
trated in vacuo. The residue was dissolved in a minimum
CH2Cl2—MeOH (50 : 1) and chromatographed on silica gel
(length 15 cm, diameter 1.5—2.0 cm) with CH2Cl2—MeOH
(50 : 1) as an eluent.
Diethyl 9Hꢀfluorenꢀ9ꢀyl phosphate, a minor product (10%)
in the synthesis of compound 15, Rf 0.30 (CH2Cl2—EtOH,
35 : 1). 1H NMR, δ: 1.36 (t, 6 H, 2 Me, J = 7.0 Hz); 4.19 (q, 4 H,
3
OCH2); 6.24 (d, 1 H, ring, JH,P = 8.9 Hz); 7.31, 7.40 (both t,
2 H each, arom., J = 7.3 Hz); 7.63, 7.73 (both d, 2 H each,
arom., J = 7.6 Hz). 31P NMR, δ: 0.41. 13C NMR, δ: 15.97 (d,
Me, 3JC,P = 7.8 Hz); 63.95 (d, OCH2, 2JC,P = 6.3 Hz); 78.02 (d,
C(1)ring, 2JC,P = 6.3 Hz); 119.84, 125.79, 127.71, 129.54, 140.33,
Diethyl 1ꢀbenzylaminoꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀylphosꢀ
phonate (2) was obtained from indanꢀ1ꢀone (1). The yield

Oneꢀpot synthesis of αꢀamino phosphonates
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
1213
141.71 (Carom). IR, ν/cm–1: 1220 (P=O). MS, m/z: 318 [M]+;
180 [M – P(O)(OEt)2]+; 152 [M – CHOP(O)(OEt)2]+; 121
[P(OEt)2]; 105 [C6H4CHO]; 76 [C6H4].
120.66, 143.02, 149.21 (Carom). IR, ν/cm–1: 1200 (Ar—OH);
1270 (P=O); 3270 (OH).
Diethyl (1ꢀbenzylaminoꢀ1ꢀcyclopropylethyl)phosphonate (19)
was obtained from cyclopropyl methyl ketone 7. The yield was
60%, Rf 0.43 (CH2Cl2—EtOH, 35 : 1). Found (%): C, 61.51;
H, 8.61. C16H26NO3P. Calculated (%): C, 61.74; H, 8.36.
1H NMR, δ: 0.50 (m, 4 H, 2 CH2,ring); 1.12 (d, 3 H, Me, J =
16.5 Hz); 1.25 (m, 1 H, CHring); 1.33, 1.36 (both t, 6 H, 2 Me,
J = 7.0 Hz); 3.97 (br.m, 2 H, CH2Ph); 4.19 (m, 4 H, OCH2);
7.23, 7.31 (both m, 5 H, arom.). 31P NMR, δ: 29.53. 13C NMR,
δ: 0.39, 0.47, 1.00 (all s, Cring); 15.37 (d, Me, J = 4.7 Hz); 16.53,
Diethyl 9ꢀbenzylaminoꢀ9,10ꢀdihydroanthracenꢀ9ꢀylphosꢀ
phonate (16) was obtained from anthrone (4). The yield was
1
20%, Rf 0.30 (CH2Cl2—EtOH, 35 : 1). H NMR, δ: 1.12, 1.27
(both t, 6 H, 2 Me, J = 6.8 Hz); 2.27 (br.m, 1 H, NH); 3.56
(HA), 3.78 (HB, AB system, 2 H, CH2Ph, 2JH,H = 13.1 Hz); 3.72
(m, 2 H, CH2,ring); 3.99, 4.05 (both m, 4 H, OCH2); 7.26, 7.34,
7.51, 7.80, 7.92 (all m, 13 H, arom.). 31P NMR, δ: 23.00.
3
13C NMR, δ: 16.12, 16.53 (both d, Me, JC,P = 6.3 Hz); 35.60
(d, CH2,ring, J = 5.2 Hz); 51.09 (d, CH2Ph, J = 18.8 Hz); 59.44
16.59 (both br.s, Me); 47.03 (s, CH2Ph); 55.21 (d, C(1), 1JC,P
=
149.4 Hz); 62.05 (s, OCH2); 126.65, 128.01, 128.15, 141.22
(Carom). IR, ν/cm–1: 1250 (P=O); 3330, 3480 (NH).
(d, C(1)ring
,
1JC,P = 154.2 Hz); 62.65, 62.83 (both d, OCH2,
2JC,P = 7.9 Hz); 126.35, 127.55, 128.35, 128.48, 129.05, 129.61,
131.90, 132.03, 133.15, 140.35 (Carom). IR, ν/cm–1: 1250 (P=O);
3300, 3470 (NH). MS, m/z: 421 [M]+.
Diethyl 2ꢀbenzylaminoꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptanꢀ
2ꢀylphosphonate (20) was obtained from camphor (8a). The yield
was 30%, Rf 0.19 (CH2Cl2—EtOH, 35 : 1). Found (%): C, 66.47;
H, 7.86; N, 3.05. C21H34NO3P. Calculated (%): C, 66.49;
H, 8.97; N, 3.69. 1H NMR, δ: 0.96, 0.98, 1.00 (all s, 9 H, 3 Me,
ring); 1.12, 1.21, 2.32 (all m, 7 H, ring); 1.27, 1.35 (both t, 6 H,
2 Me, J = 7.3 Hz); 2.28 (br.m, 1 H, NH); 3.55 (HA), 3.78 (HB,
Diethyl 9ꢀhydroxyꢀ9,10ꢀdihydroanthracenꢀ9ꢀylphosphonate,
a minor product (15%) in the synthesis of compound 16, Rf 0.21
(CH2Cl2—EtOH, 35 : 1). 1H NMR, δ: 0.95 (t, 6 H, 2 Me, J =
7.3 Hz); 3.70 (br.m, 1 H, OH); 3.82, 3.90, (both m, 4 H, OCH2);
6.83 (m, 2 H, arom.); 7.39 (m, 4 H, arom.); 7.82 (m, 2 H,
arom.). 31P NMR, δ: 21.28. IR, ν/cm–1: 1250 (P=O).
2
AB system, 2 H, CH2Ph, JH,H = 13.3 Hz); 4.05, 4.49, 4.69
Diethyl 9,10ꢀdihydroanthracenꢀ9ꢀyl phosphate was obtained
in the synthesis of compound 16. The yield was 25%, Rf 0.35
(CH2Cl2—EtOH, 35 : 1). 1H NMR, δ: 1.35 (t, 6 H, 2 Me, J =
7.3 Hz); 4.13 (q, 4 H, OCH2); 4.32 (m, 2 H, CH2,ring); 5.92 (d,
1 H, ring, J = 9.2 Hz); 6.83 (m, 2 H, arom.); 7.40 (m, 4 H,
(all m, 4 H, 2 OCH2); 7.26, 7.42 (both m, 5 H, arom.). 31P NMR,
δ: 20.49, 21.26, 22.12. 13C NMR, δ: 15.78, 15.97 (both d, Me,
3JC,P = 6.1 Hz); 22.89, 23.44, 23.70 (all s, 3 Me, ring); 50.73 (d,
CH2Ph, J = 17.3 Hz); 58.46 (m, Cring); 59,61 (d, C(1)ring, 1JC,P
=
154.2 Hz); 60.01, 62.27 (both m, Cring); 70.77, 70.85 (both br.d,
OCH2); 126.57, 127.33, 127.88, 128.36, 135.45, 138.91 (Carom).
IR, ν/cm–1: 1240 (P=O); 3320, 3340, 3420 (NH).
arom.); 7.93 (m, 2 H, arom.). 31P NMR, δ: 6.90. IR, ν/cm–1
:
1220 (P=O).
Tetraethyl [9,10ꢀbis(benzylamino)ꢀ9,10ꢀdihydroanthracenꢀ
9,10ꢀdiyl]bis(phosphonate) (17) was obtained from 9,10ꢀanthraꢀ
quinone (5). The yield was 75%, Rf 0.22 (CH2Cl2—EtOH, 35 : 1).
1H NMR, δ: 1.12, 1.27 (both t, 12 H, 4 Me, J = 7.0 Hz); 2.32
(br.m, 2 H, NH); 3.55 (HA), 3.79 (HB, AB system, 4 H, CH2Ph,
2JH,H = 12.7 Hz); 3.95, 3.99, 4.04 (all m, 8 H, 4 OCH2); 7.25,
7.30, 7.36, 7.42 (all m, 18 H, arom.). 31P NMR, δ: 25.08.
tertꢀButyl 4ꢀbenzylaminoꢀ4ꢀ(diethoxyphosphoryl)piperidineꢀ
1ꢀcarboxylate (21) was obtained from NꢀBocꢀpiperidone (9).
The yield was 99%, Rf 0.31 (CH2Cl2—EtOH, 35 : 1). Found (%)
C, 58.96; H, 8.31. C21H35N2O5P. Calculated: C, 59.15; H, 8.22.
1H NMR, δ: 1.33 (t, 6 H, 2 Me, J = 7.0 Hz); 1.45 (s, 9 H, 3 Me,
Boc); 1.82, 1.88 (both m, 4 H, 2 CH2,ring); 3.23 (m, 4 H,
2 NCH2,ring); 3.88 (br.m, 1 H, NH); 3.92 (d, 2 H, CH2Ph, J =
3.3 Hz); 4.15 (q, 4 H, 2 OCH2); 7.27, 7.35 (both m, 5 H, arom.).
31P NMR, δ: 28.68. 13C NMR, δ: 16.59, 16.71 (both d, Me,
3JC,P = 6.4 Hz); 28.40 (s, Me, Boc); 29.39 (br.s, 2 CH2,ring);
3
13C NMR, δ: 16.14, 16.33 (both d, Me, JC,P = 6.3 Hz); 51.08
1
(d, CH2Ph, J = 17.3 Hz); 59.47 (d, C(1)ring, JC,P = 154.2 Hz);
2
62.65, 62.84 (both d, OCH2, JC,P = 7.7 Hz); 126.99, 127.79,
128.24, 128.37, 128.59, 135.60, 139.21 (Carom). IR, ν/cm–1
:
38.07 (br.s, 2 NCH2,ring); 47.23 (s, CH2Ph); 54.32 (d, C(1)ring,
1250 (P=O); 3320, 3470 (NH). MS, m/z: 662 [M]+.
1JC,P = 144.6 Hz); 61.85, 62.01 (d, OCH2, JC,P = 8.0 Hz);
79.41 (s, C, Boc); 127.00, 128.12, 128.38, 140.82 (Carom); 154.84
(C=O, Boc). IR, ν/cm–1: 1250 (P=O); 1695 (C=O); 3320,
3480 (NH).
2
Tetraethyl [1,4ꢀbis(benzylamino)cyclohexaꢀ2,5ꢀdieneꢀ1,4ꢀ
diyl]bis(phosphonate) (18) was obtained from 1,4ꢀbenzoquinone
(6). The yield was 50%, Rf 0.22 (CH2Cl2—EtOH, 35 : 1).
1H NMR, δ: 1.12, 1.27 (both t, 12 H, 4 Me, J = 7.0 Hz); 2.33
(br.m, 2 H, NH); 3.54 (HA), 3.80 (HB, AB system, 4 H, CH2Ph,
2JH,H = 13.3 Hz); 3.94, 3.99, 4.07 (all m, 8 H, 4 OCH2); 7.26,
7.30, 7.36, 7.42 (all m, 14 H, arom.). 31P NMR, δ: 23.06.
Diethyl 3ꢀbenzylaminoꢀ2ꢀoxoꢀ2,3ꢀdihydroꢀ1Hꢀindolꢀ3ꢀylꢀ
phosphonate (22) was obtained from isatin (10). The yield was
90%, Rf 0.21 (CH2Cl2—EtOH, 50 : 1). Found (%): C, 60.92;
H, 6.33. C19H23N2O4P. Calculated (%): C, 60.96; H, 6.19.
1H NMR, δ: 1.12, 1.27 (both t, 6 H, 2 Me, J = 6.9 Hz); 2.56
(br.m, 1 H, NH); 3.56 (HA), 3.73 (HB, AB system, 2 H, CH2Ph,
2JH,H = 13.1 Hz); 3.80, 3.96, 4.07 (all m, 4 H, 2 OCH2); 7.26,
7.42 (both m, 9 H, arom.). 31P NMR, δ: 23.86. 13C NMR, δ:
16.08, 16.27 (both d, Me, 3JC,P = 4.6 Hz); 51.04 (d, CH2Ph, J =
3
13C NMR, δ: 16.12, 16.31 (both d, Me, JC,P = 5.9 Hz); 51.10
1
(d, CH2Ph, J = 17.6 Hz); 59.49 (d, C(1)ring, JC,P = 153.7 Hz);
2
62.68, 62.86 (both d, OCH2, JC,P = 6.6 Hz); 127.01, 127.81,
128.23, 128.36, 128.58, 135.6, 139.2 (Carom, C=C, ring).
IR, ν/cm–1: 730 (C=CH, ring); 1250 (P=O); 1400 (C=CH,
ring); 1655 (C=C); 3040 (C=CH); 3320, 3470 (NH). MS,
m/z: 562 [M]+.
18.3 Hz); 59.41 (d, C(1)ring,
1JC,P = 152.6 Hz); 62.60, 62.77
(both d, OCH2, 2JC,P = 6.1 Hz); 127.20, 128.03, 128.43, 128.55,
128.72, 128.80, 135.68, 139.33 (Carom); 159.91 (s, C=O). IR,
ν/cm–1: 1250 (P=O); 1750 (C=O); 3330, 3460 (NH).
Diethyl 4ꢀhydroxyphenyl phosphate was obtained as a byꢀ
product in the synthesis of compound 18. The yield was 50%,
Rf 0.35 (CH2Cl2—EtOH, 35 : 1). 1H NMR, δ: 1.35 (t, 6 H,
2 Me, J = 7.1 Hz); 4.19 (m, 4 H, OCH2); 6.58, 6.91 (both m,
2 H each, arom.). 31P NMR, δ: –5.89. 13C NMR, δ: 16.00 (d,
Diethyl 3ꢀhydroxyꢀ2ꢀoxoꢀ2,3ꢀdihydroꢀ1Hꢀindolꢀ3ꢀylphosꢀ
phonate, a minor product (10%) in the synthesis of compound 22,
Rf 0.15 (CH2Cl2—EtOH, 50 : 1). 1H NMR, δ: 1.19, 1.23 (both t,
6 H, 2 Me, J = 6.9 Hz); 4.02 (q, 4 H, 2 OCH2); 7.30, 7.33, 7.45,
3
2
Me, JC,P = 6.7 Hz); 64.69 (d, OCH2, JC,P = 6.1 Hz); 116.23,

1214
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 7, July, 2006
Matveeva et al.
7.48 (all s, 4 H, arom.). 13C NMR, δ: 16.40, 16.48 (both d, Me,
Russian Academy of Sciences (Basic Research Grants
1ꢀOKhNM RAN and 10ꢀOKhNM RAN).
2
3JC,P = 4.6 Hz); 63.18, 63.52 (both d, OCH2, JC,P = 7.2 Hz);
70.76 (d, C(1)ring,
1JC,P = 159.8 Hz); 125.41, 127.15, 127.26,
126.06, 128.26, 136.82 (Carom); 159.92 (s, C=O). 31P NMR, δ:
21.93. IR, ν/cm–1: 1240 (P=O); 1740 (C=O); 3330, 3280 (OH).
3ꢀBenzylaminoꢀ3ꢀdiethoxyphosphorylꢀ17ꢀ(1ꢀbenzylaminoꢀ
1ꢀdiethoxyphosphorylꢀ2ꢀhydroxyethyl)ꢀ10βꢀmethylgonaneꢀ
11β,17αꢀdiol (23) was obtained from pregnane 11. The yield
was 40%, Rf 0.15 (CH2Cl2—EtOH, 35 : 1). 1H NMR, δ: 0.67
(m, pregnane); 1.06 (s, 3 H, Me, pregnane); 1.30, 1.39 (both t,
12 H, 4 Me, J = 7.0 Hz); 1.00, 1.20, 1.26, 1.32, 1.44, 1.74, 1.98,
2.17, 2.35, 2.43, 3.35 (all m, pregnane); 3.87 (HA), 4.12 (HB,
References
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AB system, 4 H, CH2Ph, JH,H = 12.4 Hz); 4.04, 4.14, 4.21
(all m, 8 H, OCH2); 7.27, 7.34 (both m, 10 H, arom.). 31P NMR,
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Tetraethyl [1,2ꢀbis(benzylamino)ꢀ1,2ꢀdiphenylethaneꢀ1,2ꢀ
diyl]bis(phosphonate) (24) was obtained from benzil (14). The
yield was 30%, Rf 0.15 (CH2Cl2—EtOH, 50 : 1). 1H NMR, δ:
1.12, 1.27 (both t, 12 H, 4 Me, J = 7.0 Hz); 2.90 (br.m, 2 H,
2
NH); 3.56 (HA), 3.80 (HB, AB system, 4 H, CH2Ph, JH,H
=
13.3 Hz); 3.95, 4.07, 4.15 (all m, 8 H, 4 OCH2); 7.26—7.67 (m,
20 H, arom.). 31P NMR, δ: 21.94. IR, ν/cm–1: 1250 (P=O);
3320, 3460 (NH). MS, m/z: 664 [M]+.
2ꢀBenzyliminoꢀ1,2ꢀdiphenylethyl diethyl phosphate was obꢀ
tained as a byꢀproduct in the synthesis of compound 24. The
yield was 20%, Rf 0.22 (CH2Cl2—EtOH, 50 : 1). 1H NMR, δ:
1.14, 1.28 (both t, 6 H, 2 Me, J = 7.0 Hz); 3.89, 4.17 (both m,
4 H, OCH2); 4.62 (d, 2 H, CH2Ph, J = 5.7 Hz); 6.62 (d, 1 H,
3JH,P = 8.0 Hz); 7.28—7.90 (m, 15 H, arom.). 31P NMR, δ:
–2.54. IR, ν/cm–1: 1270 (P=O); 1690 (C=N).
4ꢀ(Benzylamino)pentꢀ3ꢀenꢀ2ꢀone (25) was obtained from
acetylacetone (12). The yield was 99%, Rf 0.26 (CH2Cl2—EtOH,
50 : 1). 1H NMR, δ: 1.90 (s, 3 H, Me); 2.03 (s, 3 H, COMe);
4.44 (d, 2 H, CH2Ph, J = 6.2 Hz); 5.04 (s, 1 H, CH); 7.25, 7.33
(both m, 5 H, arom.). IR, ν/cm–1: 1720 (C=O); 3300 (NH).
Ethyl 2ꢀbenzylaminocyclopentꢀ1ꢀeneꢀ1ꢀcarboxylate (26) was
obtained from oxo ester 13. The yield was 50%, Rf 0.59
(CH2Cl2—EtOH, 35 : 1). 1H NMR, δ: 1.27 (t, 3 H, Me, J =
7.0 Hz); 1.80 (m, 2 H, CH2,ring); 2.53 (t, 4 H, CH2,ring, J =
7.3 Hz); 4.15 (q, 2 H, OCH2); 4.38 (d, 2 H, CH2Ph, J = 6.3 Hz);
7.25, 7.32 (both m, 5 H, arom.); 7.77 (br.m, 1 H, NH). IR,
ν/cm–1: 1740 (C=O); 3300 (NH).
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230th ACS National Meeting (Washington, Aug. 28—Sept. 1,
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N. S. Zefirov, Tezisy dokladov Mezhdunarodnoi nauchnoꢀ
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in the Chemistry and Practical Applications of Alicyclic Comꢀ
pounds"], Samara, 2004, p. 203 (in Russian).
We are grateful to Prof. L. G. Tomilova for provided
samples of phthalocyanines.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 05ꢀ03ꢀ
33054), the Council on Grants of the President of the
Russian Federation (Program for State Support of Leadꢀ
ing Scientific Schools of the Russian Federation, Grant
NShꢀ2552.2006.3), the Ministry of Education and Sciꢀ
ence (Target Program "Development of Scientific Potenꢀ
tial of High School", Grant RNP.2.1.1.7779), and the
16. V. P. Kukhar and V. A. Solodenko, Usp. Khim., 1987, 56,
1504 [Russ. Chem. Rev., 1987, 56 (Engl. Transl.)].
Received February 16, 2006;
in revised form June 20, 2006