Aminopyridines as amino components in the catalytic synthesis of α-aminophosphonates

Article abstract of DOI:10.1007/s11172-009-0018-2

6h-Aminophosphonates containing alicyclic, aromatic, and heterocyclic fragments were obtained in high yields by the Kabachnick-Fields reaction of the corresponding carbonyl compounds with 2-, 3- and 4-aminopyridines and diethyl phosphite using tetra- tert

Full text of DOI:10.1007/s11172-009-0018-2

Russian Chemical Bulletin, International Edition, Vol. 58, No. 1, pp. 119—125, January, 2009
119
Aminopyridines as amino components in the catalytic synthesis
of αꢀaminophosphonates*
E. D. Matveeva, T. A. Podrugina, I. N. Kolesnikova, A. A. Borisenko, and N. S. Zefirov
M. V. Lomonosov Moscow State University, Department of Chemistry,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (495) 939 0290. Eꢀmail: matveeva@org.chem.msu.ru
αꢀAminophosphonates containing alicyclic, aromatic, and heterocyclic fragments were
obtained in high yields by the Kabachnick—Fields reaction of the corresponding carbonyl
compounds with 2ꢀ, 3ꢀ, and 4ꢀaminopyridines and diethyl phosphite using tetraꢀtertꢀbutylꢀ
phthalocyanine aluminum chloride as the catalyst. 2ꢀ, 3ꢀ, 4ꢀAminopyridines were found to
vary in their reactivity with ketones and diethyl phosphite in the catalytic threeꢀcomponent
oneꢀpot process.
Key words: catalysis, αꢀaminophosphonates, the Kabachnick—Fields reaction, tetraꢀ
tertꢀbutylphthalocyanine aluminum chloride, 2ꢀ, 3ꢀ, 4ꢀaminopyridines.
our investigations on the variation of both the amine and
the carbonyl components in this reaction.
We used the catalytic reaction under study for the synꢀ
thesis of αꢀaminophosphonates from aromatic and heteroꢀ
cyclic aldehydes and heterocyclic amines.
The reaction of 3ꢀaminopyridine with heterocyclic
aldehydes of the indole series, viz., Nꢀmethylindoleꢀ
2ꢀcarbaldehyde and indoleꢀ3ꢀcarbaldehyde, and diethyl
phosphite in the presence of tetraꢀtertꢀbutylphthalocyaꢀ
nine aluminum chloride (tPcAlCl) leads to the correꢀ
sponding αꢀaminophosphonates 1 and 2 in 65—70% yield
(Scheme 1, Table 1).
The last decade research on the synthesis of aminoꢀ
phosphonates is going through the renaissance. Efforts of
scientists are directed on the broadening of synthetic posꢀ
sibilities of known reactions through the application of
catalysis. These investigations are summarized in reviews.1—3
Despite of the intensive search for new approaches to the
synthesis of αꢀaminophosphonates,1—10 heterocyclic aminoꢀ
alkylphosphonates remain to be poorly available.
In the literature, there are reports on the synthesis of
heterocyclic αꢀaminophosphonates using the Kabachnick—
Fields reaction on the basis of substituted benzaldehydes
and aminopyridines as the amino component.11,12
The synthesis of the corresponding αꢀaminophosꢀ
phonates from ketones and 3ꢀaminopyridine requires longer
time. However, we found that the heating accelerates
Lately, some aminophosphonic acid derivatives on the
basis of heterocyclic aldehydes have been synthesized by
addition of the in situ forming phosphorus(III) trimethylꢀ
silyl derivatives to imines.13—15 In particular, αꢀaminoꢀ
phosphonates containing thiazole,13 furan, thiophene,14
and imidazole15 rings have been obtained. However, being
unambiguously valuable, this method requires a prelimiꢀ
nary synthesis of the starting imine and phosphorus silyl
derivatives. At the same time, in the literature there are no
reports on the synthesis of αꢀaminophosphonates on the
basis of ketones and aminopyridines.
Scheme 1
Earlier,16—20 we suggested a new threeꢀcomponent
catalytic method for the oneꢀpot synthesis of αꢀaminoꢀ
phosphonates (the Kabachnick—Fields reaction) with the
use of metalꢀcontaining tetraꢀtertꢀbutylphthalocyanines
as the catalysts, that allowed us to significantly broaden
the scope of the reaction and to involve in it ketones,
including sterically hindered. The present work continues
R =
(1),
(2)
i. Molecular sieves 4 Å.
* Dedicated to Academician A. I. Konovalov on his 75th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 119—125, January, 2009.
1066ꢀ5285/09/5801ꢀ0119 © 2009 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Matveeva et al.
Table 1. Reaction conditions and yields of αꢀaminophosphonates
based on 3ꢀaminopyridine in the threeꢀcomponent synthesis of
αꢀaminophosphonates (toluene, 110 °C)
Thus, the reaction of benzaldehyde with 2ꢀaminoꢀ
pyridine and diethyl phosphite in the presence of tPcAlCl
(Scheme 3) occurs already at room temperature in dichloroꢀ
methanе, however, the yield of the target aminophosꢀ
phonate 6 does not exceed 40% and, along with
αꢀaminophosphonate, αꢀhydroxyphosphonate 11 is formed
in 15% yield. When the temperature is increased to 110 °C
(reflux in toluene), the yield of compound 6 increases to
90% and the formation of αꢀhydroxyphosphonate 11 is
not observed.
Carbonyl
compound
Carbonyl
compound :
t/h αꢀAminoꢀ Yield
phosꢀ
(%)
: amine : HP(O)(OEt)2
phonate
1 : 1 : 1.2
1 : 1 : 1.2
1 : 1.5 : 1.2
1 : 2 : 2.4
24
24
78
99
1
2
3
4
70
65
Scheme 3
70
30*
*αꢀHydroxyphosphonate was also isolated from the reaction
mixture in 6% yield.
R = Ph (6, 11), 4ꢀPy (7),
(8, 12),
only the first step of the process, i.e., the formation of the
corresponding imines, whereas the second step of the
reaction, i.e., the addition of diethyl phosphite to imines,
is better to carry out at room temperature. Thus, under
such conditions cyclohexanone and acetophenone give
αꢀaminophosphonates 3 and 4 in 70 and 30% yield,
respectively (Scheme 2, see Table 1).
(9),
(10)
i. Molecular sieves 4 Å.
2ꢀAminopyridine with pyridineꢀ4ꢀcarbaldehyde
under analogous conditions gives the corresponding
αꢀaminophosphonate 7 in 50% yield and the formation
of αꢀhydroxyphosphonate is not observed in this case (see
Scheme 3).
Scheme 2
When heterocyclic aldehydes of the indole series
are involved into the reaction with 2ꢀaminopyridine and
t
diethyl phosphite in the presence of PcAlCl, the correꢀ
sponding αꢀaminophosphonates 8—10 are obtained in
80—91% yield, hydroxyphosphonate 12 is formed in very
low yield only in the reaction with Nꢀmethylindoleꢀ
2ꢀcarbaldehyde (see Scheme 3, Table 2).
It turned out that 4ꢀaminopyridine in the reaction
with Nꢀmethylindoleꢀ2ꢀcarbaldehyde does not give the
target αꢀaminophosphonate under conditions of this cataꢀ
lytic process, only αꢀhydroxyphosphonate 12 was isolated
from the reaction mixture in 90% yield. When indoleꢀ
3ꢀcarbaldehyde was used as the carbonyl component, a
mixture of αꢀaminophosphonate 13 and αꢀhydroxyꢀ
phosphonate 14 was obtained, the yield of which was
42 and 15%, respectively (Scheme 4, see Table 2).
Cyclohexanone and acetophenone in the reaction with
2ꢀ and 4ꢀaminopyridines and diethyl phosphite under conꢀ
i. Molecular sieves 4 Å.
3: R1 + R2 = (CH2)5; 4: R1 = Ph, R2 = Me
In contrast to 3ꢀaminopyridine, the reaction of 2ꢀ and
4ꢀaminopyridines is not so simple and even their reaction
with aldehydes affords, along with aminophosphonates,
hydroxyphosphonates as a result of competing nucleoꢀ
philic addition of diethyl phosphite to the carbonyl comꢀ
ponent.

αꢀAminophosphonates based on aminophyridines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
121
Table 2. Reaction conditions and yields of αꢀaminophosphonates and αꢀhydroxyphosphonates based on 2ꢀ and 4ꢀaminopyridines
in the threeꢀcomponent synthesis of αꢀaminophosphonates
Carbonyl
compound
Amine
Solvent
T/°C
(t/h)
Carbonyl
compound : amine :
: HP(O)(OEt)2
αꢀAminoꢀ
phosphonate
(yield (%))
αꢀHydroxyꢀ
phosphonate
(yield (%))
CH2Cl2
Toluene
20 (24)
1 : 1 : 1.2
1 : 2 : 2
6 (40)
6 (90)
11 (15)
110 (24)
—
Toluene
110 (24)
1 : 2 : 2
7 (50)
—
Toluene
DMF
110 (9)
20 (68)
1 : 1 : 1.2
1 : 1 : 1.2
8 (91)
12 (6)
—
12 (90)
Toluene
DMF
110 (24)
20 (68)
1 : 1 : 1.2
1 : 1 : 1.2
9 (80)
—
13 (42)
14 (15)
MeCN
80 (68)
1 : 1 : 1.2
10 (83)
—
Toluene
Toluene
110 (24)
110 (24)
1 : 1 : 1.2
1 : 1 : 1.2
—
—
15 (50)
15 (50)
Toluene
Toluene
110 (68)
110 (68)
1 : 1 : 1.2
1 : 1 : 1.2
—
—
5 (15)
5 (15)
Scheme 4
ditions of phthalocyanine catalysis form only the correꢀ
sponding αꢀhydroxyphosphonates 5 and 15 in 15 and 50%
yield, respectively (Scheme 5, see Table 2).
Scheme 5
R =
(12),
(13, 14)
R3 = 2ꢀPy, 4ꢀPy
i. Molecular sieves 4 Å.
15: R1 + R2 = (CH2)5

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Matveeva et al.
The Kabachnick—Fields reaction mechanism was
the case of compound 4. In the 13C NMR spectra of
all the αꢀaminophosphonates synthesized, the signal
for the Cα atom at the phosphorus atom in the region
δ 44.43—58.91 with 1JC,P = 149.3—164.7 Hz is present.
The signals for the nonisochronic ethoxy groups
at the phosphorus atom are observed in the region
δ 15.18—16.50 (3JC,P = 5.1—5.9 Hz) and δ 62.29—64.20
(2JC,P = 6.6—8.0 Hz).
Other signals in the 1H and 13C NMR spectra of
αꢀaminophosphonates correspond to the structure of the
carbon skeleton of the starting carbonyl compound and
the starting aminopyridine.
In conclusion, we found that 3ꢀaminopyridine plays
the role of the amine component in the catalytic process
of the preparation of aminophosphonates in the presence
of tPcAlCl on the basis of both the aldehydes of aromatic
and heterocyclic series and the carbоcyclic and aromatic
ketones. The 2ꢀ and 4ꢀaminopyridines afford aminoꢀ
phosphonates only with aldehydes under the conditions
selected.
widely discussed in the literature.21—23 An obvious side
process is the formation of hydroxyphosphonate (the
Abramov reaction). Two competing and reversible proꢀ
cesses take place in the threeꢀcomponent reaction: the
reaction of carbonyl compounds with amine and with
diethyl phosphite. The major direction of the process is
defined by the equilibrium constant values of the correꢀ
sponding processes, viz., the formation of imine and
αꢀhydroxyphosphonate.
We have shown that a direct amination of hydroxyꢀ
phosphonates in this process does not occur. Thus, the
reflux of αꢀhydroxyphosphonate 15 with 2ꢀ and 3ꢀaminoꢀ
pyridines under conditions of the catalytic process does
not lead to the corresponding αꢀaminophosphonates. The
results obtained are additional argument in favor of the
imine way for the reaction.
The structures of αꢀaminophosphonates obtained were
1
confirmed by the IR and Н, 13C, and 31Р NMR spectroꢀ
scopic data, their composition, by elemental analysis.
In the 31Р NMR spectra of all the αꢀaminophosphoꢀ
nates synthesized, the signals in the region δ 20.49—27.23
are present, which correspond to the surrounding sugꢀ
Experimental
1
gested for the phosphorus atom. In the Н NMR spectra
1H (400 MHz), 13C (100.61 MHz), and 31P (161.98 MHz)
NMR spectra were recorded on a Bruker Avance 400 spectroꢀ
meter in CDCl3 relatively to Me4Si as the internal standard (1H,
13C) and 85% aqueous H3PO4 as the external standard (31P). IR
spectra were recorded on a URꢀ20 spectrometer in CCl4.
Elemental analysis was performed on VarioꢀII CHN analyzer.
Aldehydes and aminopyridines (Aldrich) were used as
purchased.
Tetraꢀtertꢀbutylphthalocyanine aluminum chloride was
synthesized according to the procedure described earlier.24
Monitoring of the reaction course and purity of chromatoꢀ
graphic isolation of substances was performed by TLC on Silufol
plates. Chromatographic isolation was conducted on a columns
with silica gel Merck 60 (70—230 mesh ASTM).
of αꢀaminophosphonates 1—4, 6—10, and 13, a number
of well resolved and unoverlapped multiplets for the ethoxy
groups is present. Their number and integral intensities
correspond to the structures suggested. The signals for the
ОCН2 groups are observed as four multiplets. Recording
1
the Н NMR spectra with coupling and decoupling with
the phosphorus atom nucleus allowed us to entirely anaꢀ
lyze these multiplets and to determine all the spinꢀspin
coupling constants. On the example of compound 9 using
the Н—Н double resonance upon successive irradiation
of the Me groups, it was found that two downfield multiꢀ
plets for the ОCН2 groups with δа 3.84 and δb 4.02
1
1
correspond to the signal of the Me group at δ 1.05, whereas
to the signal for the Me group at 1.23 correspond two
multiplets at δа 4.13 and δb 4.21. The Н—H geminal
Synthesis of αꢀaminophosphonates 1, 2, 6—10, and 13
(general procedure). Amine, freshly calcined molecular sieves
4 Å (500 mg), and tPcAlCl (0.05 mmol) were added to a solution
of carbonyl compound (1 mmol) in anhydrous solvent (2 mL).
The reaction mixture was magnetically stirred for 3 h, then,
diethyl phosphite was added, the mixture was stirred until the
reaction was complete (TLC monitoring). The ratio of reagents,
the solvents used, the reaction temperatures and times, as well
as the yields of compounds obtained are given in Tables 1 and 2.
Molecular sieves 4 Å were filtered off, a precipitate was
washed with dichloromethane (3×2 mL). The solvent was
evaporated on a rotary evaporator, the residue was dissolved in
minimum dichloromethane—methanol (70 : 1) and chromatoꢀ
graphed on a column with silica gel (15 cm in length, 1.5—2.0 cm
in diameter).
2
2
constants (2JН ,Н = 10.1 Hz) and the Н—Me vicinal
а
b
constants (3JН,Me = 7.1 Hz) are the same for both pairs of
the protons. However, the spinꢀspin coupling constants
with the phosphorus atom nucleus 3JP,H considerably difꢀ
fer for the downfield and upfield protons in each diаstereoꢀ
3
topic pair. For the downfield protons, JP, а = 8.4 Hz,
Н
whereas for the upfield, 3JP, b = 7.1 Hz.
Н
The signal for the proton at Cα atom for compounds 1,
2, 6—8, and 10 appears in the region δ 5.03—6.14 as a
doublet of doublets with the spinꢀspin coupling constants
2JH,P = 18.4—23.8 Hz, 3JH,Н = 8.0—9.6 Hz or as a doublet
for compound 9 with the spinꢀspin coupling constant 2JH,P
= 20.8 Hz. The signals corresponding to the amino group
are observed as a broad multiplet in the region δ 3.46—5.81
in the case of compounds 1—3 and 6—10 and as a doublet
Diethyl [(1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)(3ꢀpyridylamino)methyl]ꢀ
phosphonate (1). M.p. 132—133 °C. Found (%): C, 61.19;
Н, 6.30; N, 11.10. C19Н24N3О3P. Calculated (%): C, 61.12;
Н, 6.48; N, 11.25. 1H NMR, δ: 1.13, 1.30 (both t, 6 Н, 2 Me,
3
POEt, JH,H = 7.1 Hz); 3.72—3.80, 3.98—4.11, 4.12—4.24 (all
3
m, 1 Н, 1 Н, 2 Н, 2 ОCН2); 3.84 (s, 3 Н, NMe); 4.93—4.98 (m,
with the spinꢀspin coupling constant JH,P = 10.6 Hz in

αꢀAminophosphonates based on aminophyridines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
123
1 Н, NH); 5.03 (dd, 1 Н, CН, 2JH,P = 22.2 Hz, 3JH,H = 8.1 Hz);
IR, ν/cm–1: 1040, 1080 (Р—О—C); 1230 (Р=О); 1460, 1480
(C=N arom.); 1550, 1580 (C=C arom.); 3310 (N—H).
4
6.69 (d, 1 Н, H(3)ind, JH,P = 3.0 Hz); 6.93 (ddd, 1 Н, H(5)Py
,
3JH,H = 8.1 Hz, 3JH,H = 2.9 Hz, 5JH,H = 1.5Hz); 7.03 (dd, 1 Н,
H(4)Py, 3JH,H = 8.3 Hz, 4JH,H = 4.5 Hz); 7.09, 7.22 (both t, 1 Н
each, H(5)ind, H(6)ind, 3JH,H = 7.6 Hz, 3JH,H = 7.5 Hz); 7.32 (d,
1 Н, H(7)ind, 3JH,H = 8.0 Hz); 7.53 (d, 1 Н, H(4)ind, 3JH,H = 7.8 Hz);
7.99 (dd, 1 Н, H(6)Py, 3JH,H = 4.6 Hz, 4JH,H = 1.2 Hz); 8.14 (d,
1 Н, H(2)Py, 4JH,H = 2.8 Hz). 31P NMR, δ: 20.49. 13C NMR, δ:
Diethyl [1ꢀphenylꢀ1ꢀ(3ꢀpyridylamino)ethyl]phosphonate (4).
3ꢀAminopyridine (2 mmol), freshly calcined molecular sieves
4 Å (500 mg), and tPcAlCl (0.05 mmol) were added to a solution
of acetophenone (1 mmol) in anhydrous toluene (2 mL). The
reaction mixture was refluxed for 3 h at 110 °C, then, molecular
sieves were filtered off, another portion of freshly calcined
molecular sieves (500 mg) was added and the mixture was refluxed
for additional 3 h. after this, diethyl phosphite (1.2 mmol) was
added into the reaction mixture and it was magnetically stirred
at room temperature for 48 h followed by addition of the second
portion of diethyl phosphite (1.2 mmol) and stirring for 48 h.
Further treatment of the reaction mixture was performed
according to general procedure for the synthesis of αꢀaminoꢀ
phosphonates 1, 2, 6—10, and 13. M.p. 112—113 °C. Found
(%): C, 61.15; Н, 7.04; N, 8.39. C17Н23N2О3Р. Calculated (%):
C, 61.07; Н, 6.93; N, 8.38. 1H NMR, δ: 1.22, 1.25 (both t, 6 Н,
3
16.26, 16.41 (both d, Me, POEt, JC,P = 5.9 Hz); 30.28 (m, M
1
e, NMe); 48.65 (d, CН, JC,P = 158.8 Hz); 63.68 (d, ОCН2,
2JC,P = 7.3 Hz); 102.52 (d, C(3)Hind 3JC,P = 5.8 Hz); 109.18
,
(C(7)Hind); 119.78, 119.83, 120.75, 121.96, 123.66 (C(4)Hind
C(5)Hind, C(6)ind, C(4)HPy, C(5)Py); 127.33, 133.39 (C(2)ind
,
,
C(9)ind); 136.79 (C(2)HPy or C(6)HPy); 138.04 (C(8)Hind);
3
140.11 (C(6)HPy or C(2)HPy); 142.34 (d, C(3)Py, JC,P = 11.7 Hz).
IR, ν/cm–1: 1035, 1060 (Р—О—C); 1240 (Р=О); 1470 (C=N arom.);
1530, 1590 (C=C arom.); 3290 (N—Н).
Diethyl [(1Hꢀindolꢀ3ꢀyl)(3ꢀpyridylamino)methyl]phosphonate
(2). M.p. 110—112 °C. Found (%): C, 60.26; Н, 6.29; N, 11.49.
C18Н22N3О3P. Calculated (%): C, 60.16; Н, 6.17; N, 11.69.
3
2 Me, POEt, 3JH,H = 7.1 Hz); 1.98 (d, 3 Н, Me, JH,P = 16.2 Hz);
3.78—4.07 (m, 4 Н, 2 ОCН2); 4.82 (d, 1 Н, NН, 3JH,P = 10.6 Hz);
3
3
1H NMR, δ: 1.01, 1.30 (both t, 6 Н, 2 Me, JH,H = 7.1 Hz);
6.55 (ddd, 1 Н, H(5)Py
,
3JH,H = 8.3 Hz, JH,H = 2.8 Hz,
3.58—3.68, 3.88—3.97, 4.11—4.25 (all m, 1 Н, 1 Н, 2 Н,
2 ОCН2); 4.68—4.72 (m, 1 Н, NH); 6.05 (dd, 1 Н, CН,
5JH,H = 1.2 Hz); 6.87 (dd, 1 Н, H(4)Py 3JH,H = 8.4 Hz,
,
4JH,H = 4.8 Hz); 7.28—7.38, 7.56—7.59 (both m, 3 Н, 2 H,
H arom.); 7.91—7.93 (m, 2 Н, H(2)Py, H(6)Py). 31P NMR, δ:
3
2JH,P = 21.4 Hz, JНH = 8.0 Hz); 6.92 (ddd, 1 Н, H(5)Py
,
3JH,H = 8.0 Hz, 3JH,H = 2.8 Hz, 5JH,H = 1.3 Hz); 7.03 (dd, 1 Н,
H(4)Py, 3JH,H = 8.4 Hz, 4JH,H = 4.5 Hz); 7.13 (t, 1 Н, H(5)ind or
25.00. 13C NMR, δ: 16.36 (d, Me, POEt, JH,P = 5.9 Hz);
3
1
20.29 (Me); 58.91 (d, CH, JC,P = 149.3 Hz); 63.63 (both d,
H(6)ind, 3JH,H = 7.0 Hz); 7.16—7.22 (m, 2 Н, H(6)ind or H(5)ind
,
ОCН2, JC,P = 7.4 Hz); 122.33, 122.95 (C(4)HPy, C(5)HPy);
2
H(2)ind); 7.34 (d, 1 Н, H(7)ind
,
3JH,H = 7.9 Hz); 7.70 (d, 1 Н,
127.70 (C(4)Harom
,
5JC,P = 3.7 Hz); 127.90 (d, C(2)Harom
,
,
H(4)ind, 3JH,H = 7.8 Hz); 7.70 (d, 1 Н, H(6)Py, 3JH,H = 3.8 Hz);
C(6)Harom
,
3JC,P = 5.1 Hz); 128.50 (d, C(3)Harom, C(5)Harom
8.14 (s, 1 Н, H(2)Py). 31P NMR, δ: 23.04. 13C NMR, δ: 16.19,
4JC,P = 3.7 Hz); 137.68 (d, C(1)arom
,
2JC,P = 5.9 Hz); 139.63,
3
3
16.48 (both d, Me, JC,P = 5.1 Hz, JC,P = 5.8 Hz); 44.51 (d,
CН, 1JC,P = 161.7 Hz); 63.25, 63.39 (both d, ОCН2, 2JC,P = 7.4 Hz);
109.57 (C(3)Hind); 111.68 (C(7)Hind); 118.94, 119.80, 119.94,
122.25, 123.68 (C(4)Hind, C(5)Hind, C(6)ind, C(4)HPy, C(5)Py);
139.15 (C(2)HPy, C(6)HPy); 141.02 (d, C(3)Py, 3JC,P = 15.3 Hz).
IR, ν/cm–1: 1030, 1070 (Р—О—C); 1230 (Р=О); 1470 (C=N),
1490 (C=C arom.), 1590 (C=C arom.), 3310 (N—H).
Diethyl (1ꢀhydroxyꢀ1ꢀphenylethyl)phosphonate (5) was isolated
as a side product in the synthesis of αꢀaminophosphonate 4.
M.p. 98—100 °C (cf. Ref. 25: m.p. 98—100 °C). 1H NMR, δ:
124.21 (d, C(2)Hind
,
3JC,P = 6.0 Hz); 126.23 (d, C(9)ind
,
,
3JC,P = 6.0 Hz); 136.48 (C(8)ind); 136.78, 139.36 (C(2)HPy
C(6)Py); 142.95 (d, C(3)Py, 3JC,P = 13.2 Hz). IR, ν/cm–1: 1045,
1060 (Р—О—C); 1240 (Р=О); 1470 (C=N arom.); 1530, 1590
(C=C arom.); 3330 (N—Н).
1.21, 1.26 (both t, 6 Н, 2 Me, POEt, JH,H = 7.0 Hz); 1.83 (d,
3
3
3 Н, Me, JH,P = 15.6 Hz); 3.88—4.13 (m, 4 Н, 2 ОCН2);
7.26—7.28, 7.61—7.3 (both m, 3 Н, 2 H, H arom.). 31P NMR,
Diethyl [1ꢀ(3ꢀpyridylamino)cyclohexyl]phosphonate (3).
3ꢀAminopyridine (1.5 mmol), freshly calcined molecular sieves
4 Å (500 mg), and tPcAlCl (0.05 mmol) were added to a solution
of cyclohexanone (1 mmol) in anhydrous toluene (2 mL). The
reaction mixture was refluxed for 6 h at 110 °C, then, diethyl
phosphite (1.2 mmol) was added and the mixture was magꢀ
netically stirred at room temperature for 72 h. Further treatment
of the reaction mixture was performed according to general
procedure for the synthesis of αꢀaminophosphonates 1, 2, 6—10,
and 13. M.p. 108—110 °C. Found (%): C, 57.58; Н, 8.06;
N, 8.84. C15Н25N2О3Р. Calculated (%): C, 57.68; Н, 8.07;
δ: 24.06. 13C NMR, δ: 16.31, 16.37 (both d, Me, POEt,
2
3JC,P = 5.8 Hz); 25.61 (d, Me, JC,P = 3.7 Hz); 63.24, 63.31
(both d, OCH2, 2JC,P = 7.3 Hz); 73.50 (d, 1 s, 1JC,P = 158.8 Hz);
125.88 (d, C(2)Harom, C(6)Harom
C(4)Нarom
,
3JC,P = 4.4 Hz); 127.33 (d,
,
5JC,P = 2.9 Hz); 127.93 (d, C(3)Harom, C(5)Harom
,
4JC,P = 2.9 Hz); 141.7 (C(1)arom). IR, ν/cm–1: 1040, 1060
(Р—О—C); 1230 (Р=О); 1470 (C=C arom.); 3300 (ОН).
Diethyl [(phenyl)(2ꢀpyridylamino)methyl]phosphonate (6).
M.p. 98—100 °C (cf. Ref. 11: m.p. 98—100 °C). 1H NMR, δ:
3
1.12, 1.25 (both t, 6 Н, 2 Me, JH,H = 7.1 Hz); 3.72—3.80,
3.92—4.03, 4.07—4.17 (all m, 1 Н, 1 H, 2 H, 2 ОCН2); 5.51 (dd,
3
N, 8.97. 1H NMR, δ: 1.23 (t, 6 Н, 2 Me, JH,H = 7.1 Hz);
1 Н, CН, 2JH,P = 21.7 Hz, 3JH,H = 9.0 Hz); 5.53—5.59 (m, 1 Н,
1.28—1.31, 1.42—1.56, 1.64—1.68, 1.77—1.85, 2.13—2.18 (all
m, 1 Н, 4 H, 1 H, 2 H, 2 H, Hcycl); 3.46—3.47 (m, 1 Н, NH);
3.96—4.11 (m, 4 Н, 2 ОCН2); 7.07 (d, 1 Н, H(4)Py, 3JH,H = 8.3 Hz,
4JH,H = 4.8 Hz); 7.51 (d, 1 Н, H(5)Py, 3JH,H = 8.3 Hz); 8.03 (d,
1 Н, H(6)Py, 3JH,H = 4.5 Hz); 8.21 (d, 1 Н, H(2)Py, 4JH,H = 2.8 Hz).
31P NMR, δ: 27.23. 13C NMR, δ: 16.50 (d, Me, 3JC,P = 5.8 Hz);
NH); 6.44 (d, 1 Н, H(3)Py,
3JH,H = 8.4 Hz); 6.59 (t, 1 Н,
H(5)Py, 3JH,H = 6.0 Hz); 7.26—7.39 (m, 5 Н, Н arom.); 7.53 (d,
1 Н, H(4)Py, 3JH,H = 7.2 Hz); 8.08 (d, 1 Н, H(6)Py, 3JH,H = 4.9 Hz).
31P NMR, δ: 22.82. 13C NMR, δ: 16.18, 16.36 (both d, Me,
1
3JC,P = 5.8 Hz); 52.77 (d, CН, JC,P = 152.2 Hz); 63.13 (d,
2
ОCН2, JC,P = 6.6 Hz); 108.47 (C(3)HPy); 113.89 (C(5)HPy);
2
19.89 (d, C(2)H2, C(6)H2, JC,P = 10.9 Hz); 25.20 (C(3)H2,
127.83, 128.05, 128.48, 136.22 (Carom); 137.37 (C(4)HPy); 147.93
1
C(5)H2); 29.95 (C(4)H2); 56.97 (d, C(1), JC,P = 161.0 Hz);
(C(6)HPy); 157.01 (d, C(2)Py, :
3JC,P = 10.9 Hz). IR, ν/cm–1
2
62.29 (d, OCH2, JC,P = 7.4 Hz); 123.25, 124.43 (C(4)HPy
,
1040, 1080 (Р—О—C); 1240 (Р=О); 1615 (C=C arom.), 3320
C(5)HPy); 140.45, 140.51 (C(2)HPy, C(6)HPy); 142.22 (C(3)Py).
(N—H).

124
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Matveeva et al.
Diethyl [4ꢀpyridyl(2ꢀpyridylamino)methyl]phosphonate (7).
M.p. 108—110 °C. Found (%): C, 56.26; Н, 6.32; N, 13.25.
1240 (Р=О); 1470 (C=N arom.); 1580, 1610 (C=C arom.);
3300 (N—Н).
C15Н20N3О3P. Calculated (%): C, 56.07; Н, 6.27; N, 13.08.
Diethyl {[1ꢀ(2ꢀcyanoethyl)ꢀ1Hꢀindolꢀ3ꢀyl](2ꢀpyridylamino)ꢀ
methyl}phosphonate (10). M.p. 147—149 °C. Found (%):
C, 61.27; H, 6.11; N, 13.65. C21H25N4O3P. Calculated (%):
C, 61.16; H, 6.11; N, 13.58. 1H NMR, δ: 1.10, 1.22 (both t, 6 Н,
2 Me, 3JH,H = 7.1 Hz); 2.66 (t, 2 Н, CН2CН2CN, 3JH,H = 6.8 Hz);
3.82—3.92, 3.39—4.16 (both m, 1 Н, 2 H, 2 ОCН2); 4.18—4.29
(m, 3 Н, CН2CН2CN, 2 ОCН2); 5.48—5.50 (m, 1 Н, NH); 6.12
3
1H NMR, δ: 1.15, 1.22 (both t, 6 Н, 2 Me, JH,H = 7.0 Hz,
3JH,H = 7.1 Hz); 3.82—3.92, 3.97—4.18 (both m, 1 Н, 3 H,
2 ОCН2); 5.64 (dd, 1 Н, CН, 2JH,P = 23.8 Hz, 3JH,H = 8.8 Hz);
5.79—5.83 (m, 1 Н, NН); 6.49 (d, 1 Н, H(3)NHPy, 3JH,H = 8.3 Hz);
6.58 (t, 1 Н, H(5)NHPy, 3JH,H = 6.0 Hz); 7.36 (t, 1 Н, H(4)NHPy
,
3JH,H = 7.7 Hz); 7.44—7.46 (m, 2 Н, H(3)Py, H(5)Py); 8.02 (d,
3
1 Н, H(6)NHPy, JH,H = 5.3 Hz); 8.53 (d, 2 Н, H(2)Py, H(6)Py
,
(dd, 1 Н, 2JH,P = 18.4 Hz, 2JH,H = 9.2 Hz); 6.45 (d, 1 Н, H(3)Py
,
3JH,H = 5.8 Hz). 31P NMR, δ: 21.51. 13C NMR, δ: 16.17, 16.34
3JH,H = 8.3 Hz); 6.57 (t, 1 Н, H(5)Py, JH,H = 5.9 Hz); 7.13 (t,
1 Н, H(5)ind or H(6)ind
3
3
3
(both d, Me, JC,P = 5.1 Hz, JC,P = 5.9 Hz); 51.77 (d, CН,
,
3JH,H = 7.4 Hz); 7.20—7.23 (m, 2 Н,
1JC,P = 150.0 Hz); 63.27, 63.51 (both d, OCH2, 2JC,P = 6.6 Hz);
H(7)ind, H(6)ind or H(5)ind); 7.32 (t, 1 Н, H(4)Py, 3JH,H = 7.7 Hz);
108.90 (C(3)HNHPy); 114.29 (C(5)HNHPy); 122.96 (d, C(3)HPy
,
7.46 (d, 1 Н, H(2)ind, ,
4JH,P = 1.8 Hz); 7.82 (d, 1 Н, H(4)ind
3
C(5)HPy JC,P = 5.1 Hz); 137.43 (C(4)HNHPy); 145.96 (C(4)Py);
147.85 (C(6)HNHPy); 149.75 (C(2)HPy, C(6)HPy); 156.56 (d,
C(2)NHPy, 3JC,P = 11.0 Hz). IR, ν/cm–1: 1040, 1060 (Р—О—C);
1240 (Р=О); 1470 (C=N arom.); 1520, 1600 (C=C arom.);
3300 (N—H).
3JH,H = 7.8 Hz); 8.15 (d, 1 Н(6)Py, 3JH,H = 5.1 Hz). 31P NMR,
δ: 23.40. 13C NMR, δ: 16.28, 16.43 (both d, Me, 3JC,P = 5.2 Hz,
3JC,P = 5.9 Hz); 18.89 (CН2CН2CN); 41.94 (CН2CН2CN);
1
44.61 (d, CН, JC,P = 161.0 Hz); 62.88, 63.21 (both d, ОCН2,
2JC,P = 6.6 Hz); 108.77, 108.83 (C(3)HPy, C(7)Hind); 111.66
Diethyl [(1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)(2ꢀpyridylamino)methyl]ꢀ
phosphonate (8). M.p. 138—140 °C. Found (%): C, 61.11;
Н, 6.57; N, 11.26. C19Н24N3О3P. Calculated (%): C, 61.12;
Н, 6.48; N, 11.25. 1H NMR, δ: 1.13, 1.23 (both t, 6 Н, 2 Me,
(C(3)ind); 113.62 (C(5)HPy); 117.13 (CN); 120.24, 120.42,
122.63 (C(4)Hind,, C(5)Hind, C(6)Hind); 127.04 (d, C(2)H
,
3JC,P = 5.8 Hz); 127.59 (d, C(9)ind
,
3JC,P = 8.0 Hz); 135i.n6d0
(C(8)ind); 137.29 (C(4)HPy); 147.77 (C(6)HPy); 157.10 (d,
3
POEt, JH,H = 7.1 Hz); 3.84—3.91, 4.05—4.23 (both m, 1 Н,
C(2)Py
,
3JC,P = 7.3 Hz). IR, ν/cm–1: 1030, 1070 (Р—О—C);
3 H, 2 ОCН2); 3.86 (s, 3 Н, NMe); 5.51—5.53 (m, 1 Н, NH);
6.14 (dd, 1 Н, CН, 2JH,P = 22.4 Hz, 3JH,H = 9.4 Hz); 6.54 (d, 1 Н,
H(3)Py, 3JH,H = 8.3 Hz); 6.61 (t, 1 Н, H(5)Py, 3JH,H = 6.0 Hz);
1220 (Р=О); 1470 (C=N arom.); 1580, 1600 (C=C arom.);
2260 (C≡N); 3300 (N—Н).
Diethyl [hydroxy(phenyl)methyl]phosphonate (11) was isolated
as a side product in the synthesis of αꢀaminophosphonate 6.
M.p. 82—83 °C (cf. Ref. 25: m.p. 82—83 °C). 1H NMR, δ: 1.22,
6.85 (s, 1 Н, H(3)ind); 7.09, 7.21 (both t, 1 Н each, H(5)ind
H(6)ind, 3JH,H = 7.4 Hz); 7.31 (d, 1 Н, H(7)ind, 3JH,H = 8.3 Hz);
7.37 (t, 1 Н, H(4)Py
3JH,H = 8.0 Hz); 7.56 (d, 1 Н, H(4)ind
3JH,H = 7.9 Hz); 8.13 (d, 1 Н, H(6)Py 3JH,H = 5.0 Hz).
31P NMR, δ: 21.65. 13C NMR, δ: 16.26, 16.41 (both d, Me,
,
3
,
,
1.27 (both t, 6 Н, 2 Me, JH,H = 7.0 Hz); 3.94—4.10 (m, 4 Н,
,
2 ОCН2); 4.39 (br.s, 1 Н, ОН); 5.03 (d, 1 Н, CН, 2JH,P = 11 Hz);
7.37—7.50 (m, 5 Н, Py). 31P NMR, δ: 21.58. IR, ν/cm–1: 1040,
1065 (Р—О—C); 1240 (Р=О); 1600 (C=C arom.); 3280 (ОН).
Diethyl [hydroxy(1ꢀmethylꢀ1Hꢀindolꢀ2ꢀyl)methyl]phosphoꢀ
nate (12) was isolated as the major product in the reaction of
Nꢀmethylindoleꢀ2ꢀcarbaldehyde, 2ꢀaminopyridine, and diethyl
phosphite according to the general procedure. M.p. 131—132 °C.
Found (%): C, 56.60; Н, 6.85; N, 4.77. C14Н20NО4P. Calculated
(%): C, 56.56; Н, 6.78; N, 4.71. 1H NMR, δ: 1.22, 1.26 (both t,
3
3
POEt, JC,P = 5.1 Hz, JC,P = 5.9 Hz); 30.15 (Me, NMe);
1
44.58 (d, CН, JC,P = 162.5 Hz); 63.19, 63.44 (both d, ОCН2,
2JC,P = 7.3 Hz); 101.92 (d, C(3)Hind 3JC,P = 4.4 Hz); 109.26,
,
109.30 (C(3)HPy, C(7)Hind); 113.99 (C(5)HPy); 119.48, 120.69,
121.66 (C(4)Hind, C(5)Hind, C(6)Hind); 127.50 (C(9)ind); 135.46
(d, C(2)ind, 3JC,P = 6.6 Hz); 137.34 (C(4)HPy); 137.52 (C(8)ind);
147.67 (C(6)HPy); 156.54 (d, C(2)Py,
3JC,P = 8.1 Hz). IR,
ν/cm–1: 1030, 1060 (Р—О—C); 1240 (Р=О); 1480 (C=N arom.);
1530, 1610 (C=C arom.); 3290 (N—Н).
6 Н, 2 Me, POEt, JH,H = 7.1 Hz); 3.78 (s, 3 Н, NMe);
3
4.00—4.16 (m, 4 Н, ОCН2); 4.70 (br.s, 1 Н, ОН); 5.18 (d, 1 Н,
Diethyl [(1Hꢀindolꢀ3ꢀyl)(2ꢀpyridylamino)methyl]phosphonate
(9). M.p. 140—141 °C. Found (%): C, 59.81; H, 5.85; N, 11.50.
C18H22N3O3P. Calculated (%): C, 60.16; H, 6.17; N, 11.69.
CН, 2JH,P = 13.9 Hz); 6.78 (s, 1 Н, H(3)ind); 7.11, 7.24 (both t,
3
1 Н each, H(5)ind, H(6)ind
,
3JH,H = 7.8 Hz, JH,H = 8.1 Hz);
7.31 (d, 1 Н, H(7)ind, ,
3JH,H = 8.3 Hz); 7.60 (d, 1 Н, H(4)ind
3
1H NMR, δ: 1.05, 1.23 (both t, 6 Н, 2 Me, JH,H = 7.1 Hz);
3JH,H = 7.9 Hz). 31P NMR, δ: 20.19. 13C NMR, δ: 16.35, 16.41
3
3.75—3.85, 3.94—4.04, 4.08—4.25 (all m, 1 Н, 1 Н, 2 H,
(both d, Me, POEt, JC,P = 5.9 Hz); 30.29 (Me, NMe);
2
1
2 ОCН2 JН ,Нb = 10.1 Hz, 3JН,Me = 7.07 Hz); 5.22—5.24 (m, 1
64.20 (d, CН, JC,P = 162.5 Hz); 63.37, 63.50 (both d, ОCН2,
а
2
3
Н, NH); 6.05 (dd, 1 Н, CН, JH,P = 20.6 Hz, JH,H = 9.1 Hz);
2JC,P = 7.3 Hz); 102.33 (d, C(3)ind 3JC,P = 4.4 Hz); 109.24
,
6.39 (d, 1 Н, H(3)Py
,
3JH,H = 8.0 Hz); 6.57 (t, 1 Н, H(5)Py
,
,
,
(C(7)ind); 119.57, 120.95, 122.04, (C(4)Hind,, C(5)Hind, C(6)Hind);
3JH,H = 6.1 Hz); 7.09, 715 (both t, 1 Н each, H(5)ind, H(6)ind
127.22 (C(9)ind); 134.80 (d, C(2)ind,
3JC,P = 5.1 Hz); 137.98
3JH,H = 7.5 Hz, JH,H = 7.6 Hz); 7.27—7.33 (m, 3 Н, H(2)ind
(C(8)ind). IR, ν/cm–1: 1030, 1065 (Р—О—C); 1240 (Р=О);
1530, 1610 (C=C arom.); 3280 (ОН).
3
H(7)ind, H(4)Py); 7.76 (d, 1 Н, H(4)ind
,
3JH,H = 7.8 Hz); 8.14
(d, 1 Н, H(6)Py
,
3JH,H = 5.0 Hz); 9.15 (br.s, 1 Н, NHind).
Diethyl [(1Hꢀindolꢀ3ꢀyl)(4ꢀpyridylamino)methyl]phosphonate
(13). M.p. 126—127 °C. Found (%): C, 60.13; Н, 6.32; N, 11.50.
C18Н22N3О3P. Calculated (%): C, 60.16; Н, 6.17; N, 11.69.
31P NMR, δ: 23.93. 13C NMR, δ: 16.19, 16.40 (both d, Me,
3JC,P = 5.1 Hz, JC,P = 5.8 Hz); 44.43 (d, CН, JC,P = 161.7
3
1
2
3
Hz); 62.93, 63.17 (both d, ОCН2, JC,P = 7.3 Hz); 108.56
1H NMR, δ: 1.08, 1.24 (both t, 6 Н, 2 Me, JH,H = 7.1 Hz);
(C(3)HPy); 110.42 (C(3)ind); 111.51 (C(7)ind); 113.70 (C(5)HPy);
119.39, 119.58, 122.06 (C(4)Hind, C(5)Hind, C(6)Hind); 124.30
(d, C(2)Hind, 3JC,P = 5.8 Hz); 126.52 (d, C(9)ind, 3JC,P = 8.0 Hz);
136.29 (C(8)ind); 137.31 (C(4)HPy); 147.79 (C(6)HPy); 157.21
(d, C(2)Py, 3JC,P = 8.8 Hz). IR, ν/cm–1: 1040, 1070 (Р—О—C);
3.76—3.86, 3.93—4.01, 4.06—4.19 (all m, 1 Н, 1 Н, 2 Н, 2 ОCН2);
2
5.36 (d, 1 Н, CН, JH,P = 20.8 Hz); 6.77 (d, 2 Н, H(3)Py
,
,
,
3
H(5)Py, JH,H = 6.5 Hz); 7.06, 7.14 (both t, 1 Н each, H(5)ind
H(6)ind, 3JH,H = 7.7 Hz, 3JH,H = 7.6 Hz); 7.38 (d, 1 Н, H(7)ind
3JH,H = 8.1 Hz); 7.47 (d, 1 Н, H(2)ind
,
4JH,P = 2.5 Hz); 7.71

αꢀAminophosphonates based on aminophyridines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
125
(d, 1 Н, H(4)ind, 3JH,H = 7.8 Hz); 8.00 (d, 2 Н, H(2)Py, H(6)Py
,
3. N. S. Zefirov, E. D. Matveeva, ARKIVOC, 2008, (i), 1.
3JH,H = 6.1 Hz). 31P NMR, δ: 21.29. 13C NMR, δ: 15.18, 15.41
(both d, Me, 3JC,P = 5.1 Hz); 46.59 (d, CН, 1JC,P = 164.7 Hz);
63.09, 63.21 (both d, ОCН2, 2JC,P = 7.3 Hz); 107.99 (C(3)Hind);
108.09 (C(3)HPy, C(5)Py); 111.19 (C(7)Hind); 118.46, 119.07,
4. V. P. Kukhar, H. R. Hudson, Aminophosphonic and Aminoꢀ
phosphinic Acids, Ed. V. P. Kukhar, John Wiley and Sons,
New York, 2000.
5. J. Uziel, J. P. Genêt, Zh. Org. Khim., 1997, 33, 1605 [Russ.
J. Org. Chem. (Engl. Transl.), 1997, 33, No. 11].
6. B. Kaboudin, R. Nazari, Tetrahedron Lett., 2001, 42, 8211.
7. J. Wu, W. Sun, H.ꢀG. Xia, X. Sun, Org. Biomol. Chem., 2006,
4, 1663.
8. B. Kaboudin, K. Moradi, Tetrahedron Lett., 2005, 46, 2989.
9. E. Van Meenen, K Moonen, D. Acke, C. Stevens, ARKIVOC,
2006, (i), 31.
10. S. Bhagat, A. K. Chakraborti, J. Org. Chem., 2007, 72, 1263.
11. A. S. Remizov, T. I. Koroleva, V. K. Promonenkov, A. F.
Grapov, Zh. Obshch. Khim., 1981, 51, 341 [J. Gen. Chem.
USSR (Engl. Transl.), 1981, 51].
12. W. Burkhouse, H. Zimmer, Synth. Commun., 1988, 18, 1347.
13. T. Olszewski, B. Boduzek, S. Sobek, H. Kozlowski, Tetraheꢀ
dron, 2006, 62, 2183.
14. B. Boduszek, D. Vegh, A. Korenova, M. Usher, Pol. J. Chem.,
2001, 75, 1271.
15. B. Boduzek, T. Olszewski, Pol. J. Chem., 2002, 76, 1619.
16. E. D. Matveeva, T. A. Podrugina, E. V. Tishkovskaya, N. S.
Zefirov, Synlett, 2003, 2321.
17. E. D. Matveeva, T. A. Podrugina, M. V. Prisyazhnoi, N. S.
Zefirov, Izv. Akad. Nauk, Ser. Khim., 2006, 1164 [Russ. Chem.
Bull., Int. Ed., 2006, 55, 1209].
121.59 (C(4)Hind, C(5)Hind, C(6)ind); 124.40 (d, C(2)Hind
3JC,P = 5.8 Hz); 126.31 (d, C(9)ind 3JC,P = 7.3 Hz); 136.49
(C(8)ind); 148.14 (C(2)HPy, C(6)Py); 153.90 (d, C(4)Py
,
,
,
3JC,P = 8.8 Hz). IR, ν/cm–1: 1040, 1065 (Р—О—C); 1240 (Р=О);
1460 (C=N arom.); 1520, 1605 (C=C arom.); 3280 (N—Н).
Diethyl [hydroxy(1Hꢀindolꢀ3ꢀyl)methyl]phosphonate (14) was
isolated as a side product in the synthesis of αꢀaminophosphonate
13. M.p. 131—132 °C. Found (%): C, 55.33; Н, 6.60 N, 4.75.
C13Н18NО4P. Calculated (%): C, 55.12; Н, 6.41; N, 4.94.
3
1H NMR, δ: 1.09, 1.24 (both t, 6 Н, 2 Me, JH,H = 7.1 Hz);
3.79—3.86, 3.92—3.99, 4.02—4.10 (all m, 1 Н, 1 Н, 2 Н,
2 ОCН2); 5.26 (d, 1 Н, CН, 2JH,P = 10.7 Hz); 7.02, 7.08 (both t,
3
1 Н each, H(5)ind, H(6)ind
7.31 (d, 1 Н, H(7)ind
,
3JH,H = 7.5 Hz, JH,H = 7.6 Hz);
,
3JH,H = 7.8 Hz); 7.36 (s, 1 Н, H(2)ind);
7.66 (d, 1 Н, H(4)ind
,
3JH,H = 7.8 Hz). 31P NMR, δ: 21.73.
3
13C NMR, δ: 14.67, 14.81 (both d, Me, JC,P = 5.1 Hz);
2
61.79, 61.87 (both d, ОCН2, JC,P = 8.0 Hz); 62.56 (d, CН,
1JC,P = 147.1 Hz); 109.13 (C(3)Hind); 110.1 (C(7)Hind); 117.70,
117.99, 120.45 (C(4)Hind, C(5)Hind, C(6)ind); 123.11 (d, C(2)Hind
,
3JC,P = 6.5 Hz); 124.94 (d, C(9)ind
,
3JC,P = 8.1 Hz); 135.01
(C(8)ind). IR, ν/cm–1: 1030, 1065 (Р—О—C); 1230 (Р=О);
1530, 1620 (C=C arom.); 3330 (ОН).
Diethyl (1ꢀhydroxycyclohexyl)phosphonate (15) was isolated
as the major product in the reaction of cyclohexanone,
2ꢀaminopyridine, and diethyl phosphite according to the general
procedure. M.p. 72—73 °C (cf. Ref. 25: m.p. 72—73 °C). 1H NMR, δ:
18. E. D. Matveeva, N. S. Zefirov, Zh. Org. Khim., 2006, 42,
1254 [Russ. J. Org. Chem. (Engl. Transl.), 2006, 42, No. 8].
19. E. D. Matveeva, T. A. Podrugina, M. V. Prisyazhnoi,
I. N. Rusetskaya, N. S. Zefirov, Izv. Akad. Nauk, Ser. Khim.,
2007, 768 [Russ. Chem. Bull., Int. Ed., 2007, 56, 798].
20. E. D. Matveeva, T. A. Podrugina, M. V. Prisyazhnoi, N. S.
Zefirov, Vestn. MGU, Ser. 2. Khim., 2007, 48, 333 [Vestn.
Mosk. Univ., Ser. Khim. (Engl. Transl.), 2007, 48, No. 5].
21. I. V. Galkina, V. I. Galkin, R. A. Cherkasov, Zh. Obshch.
Khim., 1998, 68, 1469 [Russ. J. Gen. Chem. (Engl. Transl.),
1998, 68].
3
1.17—1.25 (m, 1 Н, Hcycl); 1.30 (t, 6 Н, Me, JH,H = 7.0 Hz);
1.49—1.52, 1.60—1.70, 184—1.88 (all m, 2 Н, 5 H, 2 H, Hcycl);
3.62 (br.s, 1 Н, OH); 4.10—4.17 (m, 4 Н, 2 ОCН2). 31P NMR,
3
δ: 26.87. 13C NMR, δ: 16.52 (d, Me, JC,P = 5.1 Hz); 20.01 (d,
2
C(2)H2, C(6)H2, JC,P = 11.0 Hz); 25.34 (C(4)H2); 31.45
2
(C(3)H2, C(5)H2); 62.62 (d, OCH2, JC,P = 7.3 Hz); 70.94 (d,
1
C(1), JC,P = 164.7 Hz). IR, ν/cm–1: 1040, 1085 (Р—О—C);
1235 (Р=О); 3300 (ОН).
22. I. V. Galkina, A. A. Sobanov, V. I. Galkin, R. A. Cherkasov,
Zh. Obshch. Khim., 1998, 68, 1465 [Russ. J. Gen. Chem. (Engl.
Transl.), 1998, 68].
23. E. D. Matveeva, N. S. Zefirov, Dokl. Akad. Nauk, 2008,
420, 492 [Dokl. Chem. (Engl. Transl.), 2008].
24. S. A. Mikhalenko, S. V. Barkanova, O. L. Lebedev, E. A.
Luk´yanets, Zh. Obshch. Khim., 1971, 41, 2735 [J. Gen. Chem.
USSR (Engl. Transl.), 1971, 41].
25. V. S. Abramov, Zh. Obshch. Khim., 1952, 22, 647 [J. Gen.
Chem. USSR (Engl. Transl.), 1952, 22].
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ03ꢀ00611),
the Division of Chemistry and Materials Science of the
Russian Academy of Sciences (Programs Nos 1 and 9),
and the Presidium of the Russian Academy of Sciences
(Program No. 9P).
References
1. V. P. Kukhar´, V. A. Soldatenko, Usp. Khim., 1987, 56, 1504
[Russ. Chem. Rev. (Engl. Transl.), 1987, 56, No. 9].
2. R. A. Cherkasov, V. I. Galkin, Usp. Khim., 1998, 67, 940
[Russ. Chem. Rev. (Engl. Transl.), 1998, 67, No. 10].
Received September 4, 2008;
in revised form December 25, 2008