Catalytic hydrophosphorylation of alkyl- and acylhydrazones

Article abstract of DOI:10.1007/s11172-010-0095-2

N-Boc- and N-acylhydrazino phosphonates were obtained for the first time by hydrophos- phorylation of the appropriate hydrazones of aliphatic and aromatic aldehydes and heterocyclic and aliphatic ketones in the presence of [tetra(tert-butyl)phthalocyanine

Full text of DOI:10.1007/s11172-010-0095-2

Russian Chemical Bulletin, International Edition, Vol. 59, No. 2, pp. 418—424, February, 2010
418
Catalytic hydrophosphorylation of alkylꢀ and acylhydrazones
E. D. Matveeva, T. A. Podrugina, I. N. Kolesnikova, M. V. Prisyazhnoi, G. G. Karateev, and N. S. Zefirov
Department of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (495) 939 0290. Eꢀmail: matveeva@org.chem.msu.ru
NꢀBocꢀ and Nꢀacylhydrazino phosphonates were obtained for the first time by hydrophosꢀ
phorylation of the appropriate hydrazones of aliphatic and aromatic aldehydes and heterocyclic
and aliphatic ketones in the presence of [tetra(tertꢀbutyl)phthalocyanine]aluminum chloride as
a catalyst.
Key words: catalysts, hydrazones, phosphorylation, αꢀhydrazino phosphonates, the Puꢀ
dovik reaction, [tetra(tertꢀbutyl)phthalocyanine]aluminum chloride, phthalocyanines, alumiꢀ
num complexes.
When developing a catalytic method for the synthesis
responding αꢀhydrazino phosphonates 7—11 in 15—60%
of αꢀamino phosphonates1—3 and αꢀhydrazino phosphoꢀ
nates4 with [tetra(tertꢀbutyl)phthalocyanine]aluminum
chloride (tPcAlCl) as a catalyst, we systematically studied
the behavior of alkylꢀ and acylhydrazones of various carꢀ
bonyl compounds in catalytic hydrophosphorylation. Such
reactions produce αꢀhydrazino phosphonic acids, which
often prove to be biologically active.5
yields (Scheme 1, Table 1).
Scheme 1
The use of the Pudovik reaction for hydrophosphoryꢀ
lation of Nꢀsubstituted hydrazones has been described
hitherto in a few papers mainly focusing on variation of
the phosphorus component.6—13 The literature data on
hydrophosphorylation of Nꢀmethylꢀ and NꢀBocꢀhydrꢀ
azones are lacking; hydrophosphorylation of Nꢀacetylꢀ
hydrazones has been studied only for unsaturated aldeꢀ
hyde derivatives.6 Moreover, according to the literature
data, reactions of N,Nꢀdimethylhydrazones of aliphatic
and aromatic aldehydes,7 oꢀnitrocinnamaldehyde,8 and
isatin9 with diethyl phosphite yield no αꢀhydrazino phosꢀ
phonates.
LiClO4ꢀcatalyzed reactions of aliphatic aldehydes with
N,Nꢀdimethylhydrazine and silylated phosphite afford
αꢀhydrazino phosphonates in good yields;10 however, aroꢀ
matic aldehydes remain inert under these conditions.
They react with dimethylhydrazine and trimethyl phosꢀ
phite only in the presence of TMSCl and LiClO411 or with
tetraalkylammonium salts as catalysts.12
We found that hydrophosphorylation of propanal meꢀ
thylhydrazone (1) does not occur in such solvents as ether,
CH2Cl2, DMF, and MeCN; yet this reaction was initiatꢀ
ed when the neat hydrazone was heated with a threeꢀ
fold excess of diethyl phosphite (DEP) at 80 °C in the
presence of tPcAlCl. Under these conditions, hydrophosꢀ
phorylation of methylꢀ and dimethylhydrazones of cyꢀ
clohexanone and 3ꢀnitrobenzaldehyde gives the corꢀ
The best results were achieved in the hydrophosphoryꢀ
lation of propanal methylꢀ and dimethylhydrazones. The
yields of the corresponding αꢀhydrazino phosphonates 7
and 10 were 60 and 45%, respectively. With cyclohexꢀ
Table 1. Synthesis of αꢀhydrazino phosphonates 7—11 from
methylꢀ and dimethylhydrazones
Hydrꢀ
azone
Substituents
H : DEP* t/h
Product
(yield (%))
R1
Et
R2
R3
1
2
H
H
H
1 : 3
1 : 3
16
24
7 (60)
8 (45)
—(CH2)5—
8 (50**)
3
4
5
6
3ꢀO2NC6H4
Et
—(CH2)5—
3ꢀO2NC6H4
H
H
H
1 : 3
1 : 3
1 : 3
1 : 6
70
16
24
70
9 (30)
10 (45)
11 (15)
—
Me
Me
Me
H
* The ratio hydrazone : HP(O)(OEt)2.
** With an equimolar amount of tPcAlCl.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 409—415, February, 2010.
1066ꢀ5285/10/5902ꢀ0418 © 2010 Springer Science+Business Media, Inc.

Phosphorylation of hydrazones
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
419
Table 2. Hydrophosphorylation of NꢀBocꢀ and Nꢀacetylhydrꢀ
azones
anone methylꢀ and dimethylhydrazones, the yields of the
corresponding αꢀhydrazino phosphonates 8 and 11 decrease
to 45% and 15%, respectively, and the reaction time increasꢀ
es. Prolonged heating of 3ꢀnitrobenzaldehyde Nꢀmethylꢀ
hydrazone affords αꢀhydrazino phosphonate 9 in 30%
yield, while 3ꢀnitrobenzaldehyde N,Nꢀdimethylhydrazone
resists hydrophosphorylation under the same conditions.
With cyclohexanone methylhydrazone as an example,
we studied the influence of the amount of the catalyst on
the yields of the reaction products. We assumed that coorꢀ
dination of the resulting αꢀhydrazino phosphonate by the
central Al atom could blockade the catalyst. However, the
reaction in the presence of an equimolar amount of tPcAlCl
gave αꢀhydrazino phosphonate 8 in 50% yield, which is
comparable with its yield for a 5 mol.% charge of the
catalyst (45%). Therefore, the moderate yield of product 8
is not related to the elimination of the catalyst from the
reaction zone.
Hydrꢀ
azone
Substituents
R2
H : DEP* t/h Product
(yield (%))
R1
R3
OBut 1 : 3
12
13
14
15
16
Et
Me
H
8
11
32
8
24 (60)
25 (65)
26 (52)
27 (70)
28 (60)
28 (40**)
29 (90)
30 (55)
31 (85)
31 (60*)
32 (85)
33 (88)
34 (55)
35 (35)
Me OBut 1 : 3
OBut 1 : 6
—(CH2)4
—(CH2)5—
—(CH2)6—
OBut 1 : 3
OBut 1 : 3
17
17 —(CH2)2NBoc(CH2)2— OBut 1 : 6
18 cycloꢀC3H5
Me OBut 1 : 6
19
8
90
6
Me
Me
Me
1 : 3
20
—(CH2)5—
Me
Me
Me
Me
1 : 3
1 : 6
1 : 6
1 : 6
1.5
6
60
40
21 —(CH2)2NBoc(CH2)2—
22 cycloꢀC3H5
23 Ph
Me
H
t
Thus, using PcAlCl as a catalyst, we effected for the
first time the hydrophosphorylation of propanal, 3ꢀnitroꢀ
benzaldehyde, and cyclohexanone Nꢀmethylhydrazones
and found that 3ꢀnitrobenzaldehyde dimethylhydrazone
cannot be transformed into the corresponding αꢀhydrꢀ
azino phosphonate under these conditions.
Hydrophosphorylation of NꢀBocꢀ and Nꢀacetylhydrꢀ
azones was carried out under the same conditions as for
Nꢀalkylhydrazones (Scheme 2, Table 2).
* The ratio hydrazone : HP(O)(OEt)2.
** The reaction was carried out without a catalyst.
We found that, in contrast to Nꢀmethylꢀ and N,Nꢀdiꢀ
methylhydrazones, Nꢀacetylꢀ and NꢀBocꢀhydrazones can
be hydrophosphorylated in excess diethyl phosphite in the
absence of a solvent or a catalyst.
The advantage of the catalytic version of the reaction
was illustrated with cycloheptanone NꢀBocꢀhydrazone and
acetone Nꢀacetylhydrazone as examples. As expected, the
yields of hydrazino phosphonates 28 and 31 in the catalytꢀ
ic reaction are substantially higher than those in noncataꢀ
lytic hydrophosphorylation (see Table 2).
Scheme 2
It should be noted that the NꢀBocꢀhydrazino phosꢀ
phonates obtained are of particular interest because Bocꢀ
protection can easily be removed under the action of an
acid to give the corresponding αꢀhydrazino phosphonates
with a free hydrazine group. The latter compounds are
labile and easily decompose when stored.
With αꢀhydrazino phosphonate 29 as an example, we
eliminated both Bocꢀprotecting groups under the action
of trifluoroacetic acid and obtained αꢀhydrazino phosꢀ
phonate trifluoroacetate 36 (Scheme 3), which is a bioꢀ
isostere of the ligand to the GABAꢀreceptor14 (GABA is
gammaꢀaminobutyric acid).
The structures of αꢀhydrazino phosphonates 7—11 and
24—36 were confirmed by IR and 1H, 13C, and 31P NMR
spectroscopy and their compositions, by elemental analyꢀ
sis or mass spectrometry.
The IR spectra of all αꢀhydrazino phosphonates 7—11
and 24—36 show absorption bands at 1230—1280 (P=O)
and 3260—3390 cm–1 (N—H). For compounds 24—36,
the intense broadened bands at 1640—1695 cm–1 are due
to the carbonyl group. The 31P NMR spectra of αꢀhyꢀ
drazino phosphonates 7—11 and 24—36, the signals for
Replacement of alkyl groups by acyl ones (Boc and
acetyl) allowed the synthesis of earlier inaccessible αꢀhydrꢀ
azino phosphonates from ketone hydrazones. Their yields
are appreciably higher than those of the hydrophosphoryꢀ
lation products obtained from methylꢀ and dimethylꢀ
hydrazones (see Table 2).
The yields of Nꢀacetylhydrazino phosphonates 31—35
are comparable with, or higher than, the yields of αꢀhyꢀ
drazino phosphonates derived from NꢀBocꢀhydrazones
(e.g., compounds 31, 32). Unlike benzaldehyde NꢀBocꢀ
hydrazone, which is reluctant to catalytic hydrophosphoꢀ
rylation under these conditions, Nꢀacetylhydrazone forms
the corresponding hydrazino phosphonate 30 in 35% yield.
Acetophenone and indanone Nꢀacetylhydrazones resist
even tPcAlClꢀcatalyzed hydrophosphorylation.

420
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Matveeva et al.
Scheme 3
the IR spectra of 1ꢀ(Nꢀacetylhydrazino)cyclohexylphosꢀ
phonate 32 in CCl4 for fourfold and 40ꢀfold dilutions. The
absorption bands of the phosphoryl (1260 cm–1) and bound
NH groups (3340 cm–1) did not change in intensity or
frequency, which suggests intramolecular hydrogen bonding.
To sum up, we found the conditions for the syntheꢀ
sis of earlier unknown hydrazino phosphonates. Using
tPcAlCl as a catalyst, we hydrophosphorylated N,Nꢀdiꢀ
methylꢀ, Nꢀmethylꢀ, NꢀBocꢀ, and Nꢀacetylhydrazones.
The scope of this reaction was determined.
Experimental
NMR spectra were recorded on Bruker Avance 400 and
Bruker Avance 300 instruments (400.13 (1H), 100.61 (13C), and
161.98 MHz (31P)) in CDCl3 and DMSOꢀd6 with SiMe4 as the
internal standard (1H, 13C) and with 85% H3PO4 as the external
standard (31P). IR spectra were recorded on a URꢀ20 instrument
in CCl4. Elemental analysis was carried out on a VarioꢀII CHN
analyzer. Mass spectra were measured on a Finnigan MAT
INCOS 50 quadrupole mass spectrometer (EI, 70 eV, direct
inlet probe). Diethyl phosphite (Aldrich) was used as purchased.
[Tetra(tertꢀbutyl)phthalocyanine]aluminum chloride was preꢀ
pared according to a known procedure.16 The course of the reacꢀ
tion was monitored, and the purity of the eluates was checked,
by TLC on ALUGRAM SIL G/UV254 plates. The products were
separated by column chromatography on MN Kieselgel 60 silica
gel (0.04—0.063 mm/230—400 mesh ASTM).
the P atoms appear at δ 20—31. The proposed structures
of αꢀhydrazino phosphonates 7—11 and 24—36 agree with
their 1H and 13C NMR spectra (see Ref. 2).
In the NMR spectra of αꢀacetylhydrazino phosphoꢀ
nates 31—35, some signals are doubled. For instance, their
31P NMR spectra contain two signals for the P atom with
intensity ratios of 4 : 1 for 31—34 and 1 : 9 for 35. This
doubling can be attributed to either equilibrium between
cisꢀ and transꢀrotamers15 (structures A and B) with respect
to the hydrazide fragment or intramolecular hydrogen
bonding giving rise to two cyclic structures C and D.
Synthesis of substituted hydrazones 1—6 and 12—23 (general
procedure). A mixture of a carbonyl compound (3 mmol) and
a substituted hydrazine (3 mmol) was refluxed in hexane for
1—3 h. The reaction mixture was concentrated in vacuo and the
residue was distilled or recrystallized from ethanol to give comꢀ
pounds 1—6 and 12—23.
1ꢀMethylꢀ2ꢀpropylidenehydrazine (1). Yield 80%, b.p.
123—124 °C (cf. Ref. 17: b.p. 123 °C).
1ꢀCyclohexylideneꢀ2ꢀmethylhydrazine (2). Yield 90%, b.p.
93—95 °C (20 Torr) (cf. Ref. 18: b.p. 95 °C (20 Torr)).
1ꢀMethylꢀ2ꢀ[(3ꢀnitrophenyl)methylidene]hydrazine (3). Yield
99%, m.p. 65—66 °C (cf. Ref. 18: m.p. 66 °C).
1,1ꢀDimethylꢀ2ꢀpropylidenehydrazine (4). Yield 75%, b.p.
111—112 °C (cf. Ref. 19: b.p. 112 °C).
2ꢀCyclohexylideneꢀ1,1ꢀdimethylhydrazine (5). Yield 90%, b.p.
68—70 °C (20 Torr) (cf. Ref. 20: b.p. 70 °C (20 Torr)).
1,1ꢀDimethylꢀ2ꢀ[(3ꢀnitrophenyl)methylidene]hydrazine (6).
Yield 99%, m.p. 55—56 °C (cf. Ref. 21: m.p. 56 °C).
1ꢀtertꢀButoxycarbonylꢀ2ꢀ(1ꢀmethylethylidene)hydrazine (13).
Yield 93%, m.p. 103—104 °C (cf. Ref. 22: m.p. 100—102 °C).
1ꢀtertꢀButoxycarbonylꢀ2ꢀcyclopentylidenehydrazine (14).
Yield 82%, m.p. 123—124 °C (cf. Ref. 23: m.p. 124—125 °C).
1ꢀtertꢀButoxycarbonylꢀ2ꢀcyclohexylidenehydrazine (15). Yield
85%, m.p. 134—135 °C (cf. Ref. 23: m.p. 134—135 °C).
1ꢀtertꢀButoxycarbonylꢀ2ꢀcycloheptylidenehydrazine (16).
Yield 83%, m.p. 122—123 °C (cf. Ref. 23: m.p. 121—122 °C).
1ꢀtertꢀButoxycarbonylꢀ4ꢀ[(tertꢀbutoxycarbonyl)hydrazono]ꢀ
piperidine (17). Yield 94%, m.p. 172—173 °C (cf. Ref. 24: m.p.
172—174 °C).
1
In the H and 13C NMR spectra, the signals for the
CH3 protons of the acetyl fragment appear at δ 1.8—2.07.
They are two singlets with intensity ratios of 4 : 1 for 31—34
and 9 : 1 for 35, which correlate with the 31P NMR data.
The signal for the αꢀC atom in the 13C NMR spectra of
αꢀacetylhydrazino phosphonates 31—35 appears as two
doublets at δ 55.20—63.25 (1JC,P = 142.0—162.3 Hz); the
signal for the carbonyl C atom appears as two singlets at
δ 165—175.
IR spectroscopy revealed intramolecular hydrogen
Nꢀ(1ꢀMethylethylidene)acetohydrazide (19). Yield 93%, m.p.
bonding in αꢀacetylhydrazino phosphonates. We recorded
133—134 °C (cf. Ref. 25: m.p. 134—135 °C).

Phosphorylation of hydrazones
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
421
NꢀCyclohexylideneacetohydrazide (20). Yield 88%, m.p.
125—126 °C (cf. Ref. 26: m.p. 124 °C).
Nꢀ(1ꢀCyclopropylethylidene)acetohydrazide (22). Yield 87%,
m.p. 110—111 °C (cf. Ref. 27: m.p. 110—112 °C).
NꢀBenzylideneacetohydrazide (23). Yield 93%, m.p. 138—140 °C
(cf. Ref. 28: m.p. 139—141 °C).
(m, 9 H, 4 CH2, ring, NH); 2.55 (s, 3 H, Me, NHMe); 4.00—4.11
(m, 4 H, 2 OCH2); 6.01 (br.s, 1 H, NH). 31P NMR (CDCl3), δ:
28.10. 13C NMR (CDCl3), δ: 16.20 (d, Me, POEt, 3JC,P = 6.1 Hz);
23.20 (d, CH2, ring, 3JC,P = 19.1 Hz); 25.03 (s, CH2, ring); 30.72
2
(d, CH2, ring, JC,P = 10.4 Hz); 40.32 (s, Me, NHMe); 62.51,
2
1
62.73 (both d, POCH2, JC,P = 5.8 Hz); 65.84 (d, C, JC,P
=
1ꢀtertꢀButoxycarbonylꢀ2ꢀpropylidenehydrazine (12). Yield
= 159.3 Hz). IR, ν/cm–1: 1260 (P=O); 3250, 3340 (NH).
Found (%): C, 49.76; H, 9.45; N, 10.40. C11H25N2O3P. Calcuꢀ
lated (%): C, 49.99; H, 9.53; N, 10.60. MS, m/z: 264 [M]+, 235
[M – Et]+, 206 [M – Et – Et]+, 138 [P(OH)(OEt)2]+, 127
[M – P(O)(OEt)2]+.
1
87%, m.p. 69—70 °C. H NMR (CDCl3), δ: 1.05, 1.11 (both t,
3
3 H, Me, JH,H = 7.6 Hz); 1.46, 1.49 (both s, 9 H, But);
2.08—2.17, 2.23—2.30 (both m, 2 H, CH2); 7.17 (br.s, 1 H,
NH); 8.01 (s, 1 H, CH=N). 13C NMR (CDCl3), δ: 10.36, 10.86
(both s, Me); 19.78, 25.63 (both s, CH2); 28.26 (s, Me, But);
80.78 (s, CMe3); 147.71, 148.41 (both s, C=N); 152.77 (s, C=O).
IR, ν/cm–1: 1700 (C=N); 1720 (C=O); 3280 (N—H). Found (%):
C, 55.61; H, 9.30; N, 16.29. C8H16N2O2. Calculated (%):
C, 55.79; H, 9.36; N, 16.27.
Diethyl [(2ꢀmethylhydrazino)(3ꢀnitrophenyl)methyl]phosꢀ
phonate (9) was obtained from 1ꢀmethylꢀ2ꢀ[(3ꢀnitrophenyl)ꢀ
methylidene]hydrazine (3). The yield was 30%. 1H NMR
3
(CDCl3), δ: 1.37 (t, 6 H, 2 Me, POEt, JH,H = 7.0 Hz); 1.94
(br.s, 1 H, NH); 3.11 (s, 3 H, Me, NHMe); 3.90 (d, 1 H, CH,
2JH,P = 8.3 Hz); 4.09—4.18 (m, 4 H, 2 OCH2); 7.21 (br.s, 1 H,
NH); 7.46 (dd, 1 H, C(5)H, arom., J = 7.8 Hz, J = 8.1 Hz); 7.81
(d, 1 H, C(6)H, arom., J = 7.8 Hz); 8.03 (d, 1 H, C(4)H, arom.,
J = 8.1 Hz); 8.38 (s, 1 H, C(2)H, arom.). 31P NMR (CDCl3), δ:
22.26. 13C NMR (CDCl3), δ: 16.63 (d, Me, POEt, 3JC,P = 5.4 Hz);
42.14 (s, Me, NHMe); 55.73 (d, CH, 1JC,P = 152.9 Hz); 63.01,
63.20 (both d, POCH2, 2JC,P = 6.9 Hz); 124.87, 125.16, 129.48,
132,04, 136.22, 148.50 (all s, Carom). IR, ν/cm–1: 1250 (N=O,
NO2, P=O); 1600, 1630 (N=O, NO2); 3260, 3340 (NH).
Found (%): C, 45.24; H, 6.30; N, 13.03. C12H20N3O5P. Calcuꢀ
lated (%): C, 45.43; H, 6.35; N, 13.24. MS, m/z: 317 [M]+, 288
[M – Et]+, 259 [M – Et – Et]+, 180 [M – P(O)(OEt)2]+, 138
[P(OH)(OEt)2]+.
1ꢀtertꢀButoxycarbonylꢀ2ꢀ(1ꢀcyclopropylethylidene)hydrazine
(18). Yield 90%, m.p. 112—114 °C. 1H NMR (CDCl3), δ: 0.68—0.74
(m, 4 H, 2 CH2, ring); 1.49, 1.50 (both s, 9 H, But); 1.60 (s, 3 H,
Me) 1.68—1.75 (m, 1 H, CH, ring). 13C NMR (CDCl3), δ: 4.83,
5.25 (both s, CH2, ring); 9.96, 12.01 (both s, CH, ring); 18.04,
20.25 (both s, Me); 28.27 (s, Me, But); 80.78 (s, CMe3); 152.87
(s, C=O); 153.2 (s, C=N). IR, ν/cm–1: 1630 (C=N); 1690
(C=O); 3250 (N—H). Found (%): C, 60.37; H, 9.36; N, 13.93.
C10H18N2O2. Calculated (%): C, 60.58; H, 9.15; N, 14.13.
4ꢀAcetylhydrazonoꢀ1ꢀtertꢀbutoxycarbonylpiperidine (21).
Yield 89%, m.p. 129—131 °C. 1H NMR (CDCl3), δ: 1.46 (s, 9 H,
But); 2.23 (s, 3 H, Me, Ac); 2.40—2.47 (m, 4 H, NCH2CH2,
ring); 3.55 (br.m, 4 H, NCH2CH2, ring); 9.61 (br.s, 1 H, NHAc).
13C NMR, δ: 20.47 (s, Me, Ac); 26.77 (s, NCH2CH2, ring);
28.40 (s, Me, But); 33.78 (s, NCH2CH2, ring); 80.11 (s, CMe3);
151.25 (s, C=O, Boc); 154.60 (s, C=N); 174.24 (s, C=O, Ac).
IR, ν/cm–1: 1640 (C=N); 1670, 1690 (C=O); 3240 (N—H).
MS, m/z: 255 [M]+.
Diethyl [1ꢀ(2,2ꢀdimethylhydrazino)propyl]phosphonate (10)
was obtained from 1,1ꢀdimethylꢀ2ꢀpropylidenehydrazine (4).
The yield was 45%. 1H NMR (CDCl3), δ: 1.01 (t, 3 H, Me,
J = 7.1 Hz); 1.26, 1.28 (both t, 6 H, 2 Me, POEt, 3JH,H = 7.0 Hz);
2
1.55—1.94 (m, 2 H, CH2); 2.73 (d, 1 H, CH, JH,P = 10.2 Hz);
Synthesis of αꢀhydrazino phosphonates 7—11 and 24—35
(general procedure). A mixture of a hydrazone (1 mmol), diethyl
phosphite (3—6 mmol), and PcAlCl (0.05 mmol) was stirred
under argon at 80 °C until the reaction was completed (monitorꢀ
ing by TLC). Then the mixture was diluted with CH2Cl2—MeOH
(70 : 1, 2 mL) and chromatographed on silica gel (column height
15 cm, column diameter 1.5—2.0 cm). The ratios of the reꢀ
agents, the reaction times, and the yields of the products are
given in Tables 1 and 2.
3.01 (s, 6 H, Me, NMe2); 3.99—4.13 (m, 4 H, 2 OCH2).
31P NMR (CDCl3), δ: 24.69. 13C NMR (CDCl3), δ: 16.99
(d, Me, POEt, 3JC,P = 4.8 Hz); 21.39 (s, Me); 43.04 (br.s, CH2);
t
1
47.98 (s, Me, NMe2); 56.92 (d, CH, JC,P = 147.0 Hz); 62.23,
62.76 (both d, POCH2, 2JC,P = 6.8 Hz). IR, ν/cm–1: 1260 (P=O);
3290, 3360 (NH). Found (%): C, 45.20; H, 9.84; N, 11.59.
C9H23N2O3P. Calculated (%):C, 45.37; H, 9.73; N, 11.76. MS,
m/z: 238 [M]+, 209 [M – Et]+, 180 [M – Et – Et]+, 138
[P(OH)(OEt)2]+, 101 [M – P(O)(OEt)2]+.
Diethyl [1ꢀ(2ꢀmethylhydrazino)propyl]phosphonate (7) was
obtained from 1ꢀmethylꢀ2ꢀpropylidenehydrazine (1). The yield
was 60%. 1H NMR (CDCl3), δ: 0.92 (t, 3 H, Me, 3JH,H = 7.3 Hz);
1.29, 1.30 (both t, 6 H, 2 Me, POEt, 3JH,H = 7.1 Hz); 1.52—1.70
Diethyl [1ꢀ(2,2ꢀdimethylhydrazino)cyclohexyl]phosphonate
(11) was obtained from 2ꢀcyclohexylideneꢀ1,1ꢀdimethylhydrꢀ
azine (5). The yield was 15%. H NMR (CDCl3), δ: 1.09—1.26
1
(m, 2 H, CH2, ring); 1.27, 1.29 (both t, 6 H, 2 Me, POEt,
3JH,H = 7.0 Hz); 1.35—1.80 (m, 8 H, 4 CH2, ring); 2.93 (s, 6 H,
2 Me, NMe2); 4.05—4.16 (m, 4 H, 2 OCH2). 31P NMR (CDCl3),
δ: 28.19. 13C NMR (CDCl3), δ: 16.19 (d, Me, POEt, 3JC,P = 6.1 Hz);
23.01 (d, CH2, ring, 3JC,P = 19.0 Hz); 25.13 (s, CH2, ring); 31.61
2
(m, 3 H, CH2, NH); 2.75 (d, 1 H, CH, JH,P = 10.3 Hz); 2.84
(s, 3 H, Me, NHMe); 4.06—4.14 (m, 4 H, 2 OCH2); 5.79 (br.s,
1 H, NH). 31P NMR (CDCl3), δ: 24.44. 13C NMR (CDCl3), δ:
3
16.27 (d, Me, POEt, JC,P = 6.6 Hz); 19.04 (s, Me); 39.84
(s, Me, NHMe); 43.27 (d, CH2, 2JC,P = 19.7 Hz); 58.44 (d, CH,
1JC,P = 154.6 Hz); 62.31, 62.50 (both d, POCH2, 2JC,P = 5.8 Hz).
IR, ν/cm–1: 1260 (P=O); 3260, 3350 (NH). Found (%): C, 42.70;
H, 9.31; N, 12.29. C8H21N2O3P. Calculated (%): C, 42.85;
H, 9.44; N, 12.49. MS, m/z: 224 [M]+, 195 [M – Et]+, 166
[M – Et – Et]+, 138 [P(OH)(OEt)2]+, 87 [M – P(O)(OEt)2]+.
Diethyl [1ꢀ(2ꢀmethylhydrazino)cyclohexyl]phosphonate (8)
was obtained from 1ꢀcyclohexylideneꢀ2ꢀmethylhydrazine (2).
The yield was 45%. 1H NMR, δ: 1.11—1.27 (m, 2 H, CH2, ring);
1.32, 1.34 (both t, 6 H, 2 Me, POEt, 3JH,H = 7.0 Hz); 1.40—1.81
(d, CH2, ring, JC,P = 10.2 Hz); 45.88 (s, Me, NMe2); 62.41,
2
2
1
62.63 (both d, POCH2, JC,P = 6.4 Hz); 66.74 (d, C, JC,P
=
= 159.1 Hz). IR, ν/cm–1: 1260 (P=O); 3290, 3360 (NH).
Found (%): C, 51.54; H, 9.92; N, 9.90. C12H27N2O3P. Calcuꢀ
lated (%):C, 51.78; H, 9.78; N, 10.06. MS, m/z: 278 [M]+, 249
[M – Et]+, 220 [M – Et – Et]+, 141 [M – P(O)(OEt)2]+,138
[P(OH)(OEt)2]+.
Diethyl [1ꢀ(2ꢀtertꢀbutoxycarbonylhydrazino)propyl]phosꢀ
phonate (24) was obtained from hydrazone 12. The yield was
1
3
60%. H NMR (CDCl3), δ: 1.06 (t, 3 H, Me, JH,H = 7.5 Hz);

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Matveeva et al.
1
1.27, 1.28 (both t, 3 H each, 2 Me, POEt, 3JH,H = 7.2 Hz); 1.39
(s, 9 H, But); 1.51—1.62, 1.68—1.82 (both m, 1 H each, CH2);
3.00—3.06 (m, 1 H, CH); 3.84 (br.s, 1 H, NHNHBoc); 4.06—4.13
(m, 4 H, 2 OCH2); 6.48 (br.s, 1 H, NHNHBoc). 31P NMR
CH2, ring); 61.81 (d, C, JC,P = 141.9 Hz); 62.32 (d, OCH2,
2JC,P = 8.1 Hz); 79.63 (s, CMe3); 156.31 (s, C=O). IR, ν/cm–1
:
1030, 1060 (P—O—C); 1260 (P=O); 1710, 1740 (C=O);
3300, 3390 (N—H). Found (%): C, 52.53; H, 9.00; N, 7.58.
C16H33N2O5P. Calculated (%): C, 52.73; H, 9.13; N, 7.69.
1ꢀtertꢀButoxycarbonylꢀ4ꢀ(2ꢀtertꢀbutoxycarbonylhydrazino)ꢀ
4ꢀ(diethoxyphosphoryl)piperidine (29) was obtained from hydrꢀ
azone 17. The yield was 90%. 1H NMR (CDCl3), δ: 1.33 (t, 6 H,
(CDCl3), δ: 26.73. 13C NMR (CDCl3), δ: 11.10 (d, Me; 3JH,P
=
= 9.7 Hz); 16.50 (br.s, Me, POEt); 21.22 (s, CH2); 28.34 (s, Me,
1
But); 59.47 (d, CH, JC,P = 155.0 Hz); 61.99, 62.41 (both d,
OCH2, 2JC,P = 7.2 Hz, 2JC,P = 6.4 Hz); 80.45 (s, CMe3); 156.24
(s, C=O). IR, ν/cm–1: 1030, 1070 (P—O—C); 1260 (P=O); 1710
(C=O); 3290 (N—H). Found (%): C, 46.35; H, 8.73; N, 9.15.
C12H27N2O5P. Calculated (%): C, 46.44; H, 8.77; N, 9.03.
Diethyl [1ꢀ(2ꢀtertꢀbutoxycarbonylhydrazino)ꢀ1ꢀmethylethyl]ꢀ
phosphonate (25) was obtained from hydrazone 13. The yield
was 65%. 1H NMR (CDCl3), δ: 1.22 (d, 6 H, 2 Me, 3JH,P = 15.7 Hz);
1.27 (t, 6 H, 2 Me, POEt, 3JH,H = 7.1 Hz, 3JH,3H = 7.3 Hz); 1.37
(s, 9 H, But); 3.90 (br.d, 1 H, NHNHBoc, JH,H = 9.6 Hz);
4.06—4.12 (m, 4 H, 2 OCH2); 6.57 (br.s, 1 H, NHNHBoc).
31P NMR (CDCl3), δ: 29.37. 13C NMR (CDCl3), δ: 16.47
(d, Me, POEt, 3JC,P = 5.1 Hz); 20.75 (s, Me); 28.21 (s, Me, But);
56.38 (d, CH, 1JC,P = 150.0 Hz); 62.40 (d, OCH2, 2JC,P = 7.3 Hz);
79.87 (s, CMe3); 156.68 (s, C=O). IR, ν/cm–1: 1040, 1060
(P—O—C); 1260 (P=O); 1740 (C=O); 3260, 3340 (NH).
Found (%): C, 46.51; H, 8.64; N, 8.95. C12H27N2O5P. Calcuꢀ
lated (%): C, 46.44; H, 8.77; N, 9.03.
2 Me, POEt, JH,H = 7.1 Hz); 1.42, 1.43 (both s, 18 H, 2 But);
3
1.59—1.72, 1.74—1.90 (both m, 2 H each, NCH2CH2); 3.23—3.43
(m, 2 H, NCH2CH2); 3.70—3.95 (m, 3 H, NCH2CH2, NHNHꢀ
Boc); 4.10—4.19 (m, 4 H, 2 OCH2); 6.85 (br.s, 1 H, NHNHBoc).
31P NMR (CDCl3), δ: 27.01. 13C NMR (CDCl3), δ: 16.60
3
(d, Me, POEt, JC,P = 4.0 Hz); 27.51 (s, NCH2CH2, ring);
28.35, 28.49 (both s, Me, But, BocꢀN(CH2)2, BocNH); 37.71,
38.53 (both br.s, NCH2CH2, ring); 56.92 (d, C, 1JC,P = 148.6 Hz);
62.69 (d, POCH2, 2JC,P = 7.3 Hz); 79.43, 80.13 (both s, CMe3,
BocꢀN(CH2)2, BocNH); 154.75, 156.01 (both s, C=O, Bocꢀ
N(CH2)2, BocNH). IR, ν/cm–1: 1060, 1080 (P—O—C); 1260
(P=O); 1690, 1730 (C=O); 3290, 3320 (N—H). Found (%):
C, 50.49; H, 8.32; N, 9.23. C16H33N2O5P. Calculated (%):
C, 50.54; H, 8.48; N, 9.31.
Diethyl [1ꢀ(2ꢀtertꢀbutoxycarbonylhydrazino)ꢀ1ꢀcycloproꢀ
pylethyl]phosphonate (30) was obtained from hydrazone 18. The
yield was 55%. 1H NMR (CDCl3), δ: 0.40—0.45, 0.47—0.55
Diethyl [1ꢀ(2ꢀtertꢀbutoxycarbonylhydrazino)cyclopentyl]ꢀ
phosphonate (26) was obtained from hydrazone 14. The yield
was 52%. 1H NMR (CDCl3), δ: 1.29 (t, 6 H, 2 Me, POEt,
3JH,H = 7.1 Hz); 1.38 (s, 9 H, But); 1.56—1.73, 1.78—1.91 (both
m, 4 H each, ring); 3.73 (br.s, 1 H, NHNHBoc); 4.07—4.15
(m, 4 H, 2 OCH2); 6.73 (br.s, 1 H, NHNHBoc). 31P NMR
(CDCl3), δ: 29.91. 13C NMR (CDCl3), δ: 16.52 (d, Me, POEt,
3
(both m, 4 H, CH2, ring); 0.97, 0.99 (both d, 3 H, Me, JH,P
=
3
= 16.2 Hz, JH,P = 16.1 Hz); 1.12—1.19 (m, 1 H, CH, ring);
1.32—1.37 (m, 6 H, 2 Me, POEt); 1.41, 1.42 (both s, 9 H, But);
4.01 (br.s, 1 H, NHNHBoc); 4.13—4.23 (m, 4 H, 2 OCH2); 6.54
(br.s, 1 H, NHNHBoc). 31P NMR (CDCl3), δ: 28.51, 29.63.
13C NMR (CDCl3), δ: 0.15 (d, CH2, ring, 3JC,P = 8.0 Hz); 1.52
(s, CH2, ring); 13.78 (br.s, Me, CH, ring); 16.58 (br.s, Me,
POEt); 28.33 (s, Me, But); 58.83 (d, C, 1JC.P = 152.6 Hz); 62.46,
3
3JC,P = 5.2 Hz); 24.52 (d, CH2, ring, JC,P = 11.0 Hz); 28.23
2
(s, Me, But); 32.20 (d, CH2, ring, JC,P = 4.4 Hz); 62.31
(d, OCH2, 2JC,P = 7.3 Hz); 66.32 (d, C, 1JC,P = 152.3 Hz); 79.74
(s, CMe3); 156.45 (s, C=O). IR, ν/cm–1: 1040, 1060 (P—O—C);
1255 (P=O); 1740 (C=O); 3290, 3390 (N—H). Found (%):
C, 50.17; H, 8.71; N, 8.18. C14H29N2O5P. Calculated (%):
C, 49.99; H, 8.69; N, 8.33.
62.74 (both d, OCH2, JC,P = 7.3 Hz); 79.95 (s, CMe3); 156.61
2
(s, C=O). IR, ν/cm–1: 1040, 1060 (P—O—C); 1260 (P=O); 1720,
1740 (C=O); 3300 (N—H). Found (%): C, 50.24 ; H, 8.85;
N, 8.58. C14H29N2O5P. Calculated (%): C, 49.99; H, 8.69;
N, 8.33.
Diethyl [1ꢀ(2ꢀtertꢀbutoxycarbonylhydrazino)cyclohexyl]ꢀ
phosphonate (27) was obtained from hydrazone 15. The yield
was 70%. 1H NMR (CDCl3), δ: 1.14—1.24 (m, 1 H, ring); 1.30
(t, 6 H, 2 Me, POEt, 3JH,H = 7.1 Hz), 1.39—1.43 (m, 1 H, ring);
1.40 (s, 9 H, But); 1.55—1.63 (m, 3 H, ring); 1.73—1.80 (m, 4 H,
ring); 3.77 (br.s, 1 H, NHNHBoc); 4.06—4.15 (m, 4 H, 2 OCH2);
6.79 (br.s, 1 H, NHNHBoc). 31P NMR (CDCl3), δ: 29.07.
Diethyl [1ꢀ(2ꢀacetylhydrazino)ꢀ1ꢀmethylethyl]phosphonate
(31) was obtained from Nꢀ(1ꢀmethylethylidene)acetohydrazide
(19). The yield was 85%. 1H NMR (CDCl3), δ: 1.28, 1.30 (both
d, 6 H, 2 Me, 3JH,P = 15.2 Hz, 3JH,P = 15.7 Hz); 1.34, 1.35 (both
t, 6 H, 2 Me, POEt, 3JH,H = 7.0 Hz, 3JH,H = 7.1 Hz); 1.97, 2.08
(both s, 3 H, Me, Ac); 4.13—4.21 (m, 5 H, 2 OCH2 NHNHAc);
7.83 (br.s, 1 H, NHNHAc). 31P NMR (CDCl3), δ: 28.75, 29.75.
13C NMR (CDCl3), δ: 16.53 (both d, Me, POEt, 3JC,P = 4.1 Hz);
19.59, 21.05 (both s, C(O)CH3); 21.06 (s, Me); 55.89, 56.62
3
13C NMR (CDCl3), δ: 16.54 (d, Me, POEt, JC,P = 5.1 Hz);
19.76 (d, CH2, ring, 3JC,P = 10.3 Hz); 25.37, 27.60 (both s, CH2,
1
1
1
ring); 28.26 (s, Me, But); 58.33 (d, C, JC,P = 145.6 Hz); 62.31
(both d, C, JC,P = 143.0 Hz, JC,P = 160.6 Hz); 62.69, 62.84
2
2
2
(d, OCH2, JC,P = 7.4 Hz); 79.65 (s, CMe3); 155.91 (s, C=O).
(both d, OCH2, JC,P = 7.3 Hz, JC,P = 7.2 Hz); 168.38 175.83
(both s, C=O). IR, ν/cm–1: 1040, 1065 (P—O—C); 1250 (P=O);
1640, 1660 (C=O); 3280 (N—H). Found (%): C, 42.83; H, 8.57;
N, 11.13. C9H21N2O4P. Calculated (%): C, 42.85; H, 8.39;
N, 11.11.
IR, ν/cm–1: 1030, 1050 (P—O—C); 1260 (P=O); 1735
(C=O); 3290 (N—H). Found (%): C, 51.71; H, 8.70; N, 7.88.
C15H31N2O5P. Calculated (%): C, 51.42; H, 8.92; N, 7.99.
Diethyl [1ꢀ(2ꢀtertꢀbutoxycarbonylhydrazino)cycloheptyl]ꢀ
phosphonate (28) was obtained from hydrazone 16. The yield
Diethyl [1ꢀ(2ꢀacetylhydrazino)cyclohexyl]phosphonate (32)
was obtained from Nꢀcyclohexylideneacetohydrazide (20). The
yield was 85%. 1H NMR (CDCl3), δ: 1.04—1.07 (m, 1 H, ring);
1.28, 1.30 (both t, 6 H, 2 Me, POEt, 3JH,H = 7.1 Hz); 1.40—1.89
(m, 9 H, ring); 1.89, 2.12 (both s, 3 H, Me); 4.06—4.15 (m, 4 H,
2 OCH2); 3.95 (br.s, 1 H, NHNHAc); 8.01 (br.s, 1 H,
NHNHAc). 31P NMR (CDCl3), δ: 27.87, 29.19. 13C NMR
1
was 60%. H NMR (CDCl3), δ: 1.28, 1.29 (both t, 6 H, 2 Me,
POEt, 3JH,H = 7.1 Hz); 1.38 (br.s, 9 H, But); 1.42—1.58 (m, 6 H,
ring), 1.59—1.76 (m, 4 H, ring); 1.59—1.76 (m, 2 H, ring); 3.67
(br.s, 1 H, NHNHBoc); 4.07—4.12 (m, 4 H, 2 OCH2); 6.74
(br.s, 1 H, NHNHBoc). 31P NMR (CDCl3), δ: 30.74. 13C NMR
(CDCl3), δ: 16.47 (d, Me, POEt, 3JC,P = 5.8 Hz); 22.15 (d, CH2,
3
3
ring, JC,P = 8.8 Hz); 28.25 (s, Me, But); 30.66, 31.54 (both s,
(CDCl3), δ: 16.39, 16.45 (both d, Me, POEt, JC,P = 5.1 Hz);

Phosphorylation of hydrazones
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
423
19.39, 21.11 (both s, C(O)CH3); 19.72, 19.99 (both d, CH2,
ature for 4 h. The solvent and the trifluoroacetic acid were reꢀ
moved on a rotary evaporator to a constant weight. The yield of
salt 36 was 475 mg (99%), a slightly yellowish oil. 1H NMR
(DMSOꢀd6), δ: 1.20, 1.23 (both t, 6 H, 2 Me, POEt, 3JH,H = 7.2 Hz);
1.85—2.20 (m, 5 H, 2 CH2, ring, NH); 3.12—3.37 (m, 4 H,
2 CH2, ring); 4.08, 4.16 (both dq, 4 H, 2 OCH2, 3JH,P = 8.7 Hz,
3JH,H = 7.2 Hz); 4.62 (br.s, 2 H, NH, ring, NH2). 31P NMR
(DMSOꢀd6), δ: 27.27, 28.43. 13C NMR (DMSOꢀd6), δ: 18.36,
18.45 (both d, Me, POEt, 3JC,P = 5.7 Hz); 27.02 (s, CH2, ring);
3
ring, JC,P = 10.9 Hz); 25.01, 27.37 (both s, CH2, ring); 57.76,
1
1
58.35 (both d, C, JC,P = 142.0 Hz, JC,P = 161.0 Hz), 62.47,
2
62.66 (both d, OCH2, JC,P = 7.4 Hz); 166.81, 174.99 (both s,
C=O). IR, ν/cm–1: 1040, 1070 (P—O—C); 1230 (P=O); 1665
(C=O); 3280 (N—H). Found (%): C, 49.24; H, 8.68; N, 9.35.
C12H25N2O4P. Calculated (%): C, 49.31; H, 8.62; N, 9.58.
4ꢀ(2ꢀAcetylhydrazino)ꢀ1ꢀtertꢀbutoxycarbonylꢀ4ꢀ(diethoxyꢀ
phosphoryl)piperidine (33) was obtained from hydrazone 21. The
yield was 88%. 1H NMR (CDCl3), δ: 1.33 (t, 6 H, 2 Me, POEt,
3JH,H = 7.1 Hz); 1.42, 1.44 (both s, 9 H, But); 1.69—1.90 (m, 4 H,
CH2CH2N); 1.94, 2.15 (both s, 3 H, Me); 3.17—3.30, 3.71—3.90
(both m, 2 H each, CH2CH2N, ring); 4.12—4.20 (m, 4 H,
OCH2); 4.62 (br.s, NHNHAc); 7.96 (s, NHNHAc). 31P NMR
(CDCl3), δ: 26.27, 27.24. 13C NMR (CDCl3), δ: 16.55 (d, Me,
2
40.37, 40.85 (both d, CH2, ring, JC,P = 8.0 Hz), 55.63, 57.23
1
(both d, C, JC,P = 150.9 Hz); 67.47, 68.19 (both d, POCH2,
2JC,P = 8.0 Hz). MS, m/z: 251 [M]+, 181 [NH2—NH=CH—
—P(O)(OEt)2]+.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ03ꢀ00611),
the Russian Academy of Sciences (Basic Research Proꢀ
grams 1ꢀOKhNM and 9ꢀOKhNM), and the Presidium of
the Russian Academy of Sciences (Grant 9P).
3
POEt, JC,P = 4.0 Hz); 19.67, 21.29 (both s, C(O)CH3); 27.45
(s, CH2CH2N); 28.45 (s, Me, But); 37.81, 38.50 (both br.s,
1
1
CH2CH2N); 56.44, 56.99 (both d, C, JC,P = 147.0 Hz, JC,P
=
2
= 160.6 Hz); 63.04 (d, OCH2, JC,P = 7.2 Hz); 79.60, 79.91
(both s, CMe3); 154.72 (s, C=O, Boc); 168.03, 174.78 (both s,
C=O, Ac). IR, ν/cm–1: 1040, 1060 (P—O—C); 1255 (P=O); 1670,
1685 (C=O); 3280 (N—H). Found (%): C, 48.81; H, 8.18; N, 10.56.
C16H32N3O6P. Calculated (%): C, 48.85; H, 8.20; N, 10.68.
Diethyl [1ꢀ(2ꢀacetylhydrazino)ꢀ1ꢀcyclopropylethyl]phosꢀ
phonate (34) was obtained from hydrazone 22. The yield was
55%. 1H NMR (CDCl3), δ: 0.37—0.54 (m, 4 H, CH2, ring);
0.89, 0.96 (both d, 3 H, Me, 3JH,P = 16.2 Hz, 3JH,P = 15.9 Hz);
1.14—1.22 (m, 1 H, CH, ring); 1.30, 1.31 (both t, 6 H, 2 Me,
POEt, 3JH,H = 7.1 Hz); 1.92, 2.04 (both s, 3 H, Me); 4.07—4.22
(m, 4 H, 2 OCH2); 4.91 (br.s, 1 H, NHNHAc); 7.86 (br.s, 1 H,
NHNHAc). 31P NMR (CDCl3), δ: 27.91, 28.67. 13C NMR
References
1. E. D. Matveeva, T. A. Podrugina, E. V. Tishkovskaya, N. S.
Zefirov, Synlett., 2003, 2321.
2. 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].
3. N. S. Zefirov, E. D. Matveeva, ARKIVOC, 2008, (i), No. 1,
1—17.
4. E. D. Matveeva, T. A. Podrugina, I. N. Kolesnikova, N. S.
Zefirov, Izv. Akad. Nauk, Ser. Khim., 2010, 571 [Russ. Chem.
Bull., Int. Ed., 2010, 59, No. 3].
3
(CDCl3), δ: –0.30, 0.33 (both d, CH2, ring, JC,P = 9.6 Hz,
3JC,P = 8.0 Hz); 1.16, 2.03 (both s, CH2, ring); 13.25, 13.38
(both s, CH3); 13.54, 14.62 (both s, CH, ring); 16.46, 16.52
(both d, Me, POEt, 3JC,P = 5.6 Hz, 3JC,P = 4.9 Hz); 19.60, 20.97
5. P. Diel, L. Maier, Eur. Pat. Appl. EP, 1985, 143 078; Chem.
Abstr., 1985, 103, 215544m.
6. C. Stevens, E. Meenen, K. Masschelein, K. Moonen,
A. Blieck, Synlett., 2007, 2549.
1
(both s, C(O)CH3); 57.79, 59.15 (both d, C, JC,P = 145.3 Hz,
2
1JC,P = 163.0 Hz); 62.49, 62.44, 63.17 (all d, OCH2, JC,P
=
= 7.2 Hz); 167.77, 175.84 (both s, C=O). IR, ν/cm–1: 1030,
1065 (P—O—C); 1240 (P=O); 1670 (C=O); 3280 (N—H).
Found (%): C, 47.23; H, 8.44; N, 10.23. C11H23N2O4P. Calcuꢀ
lated (%): C, 47.48; H, 8.33; N, 10.07.
7. L. V. Ryapisova, L. B. Kashevarova, S. V. Fridland, I. G.
Shaikhiev, Zh. Obshch. Khim., 2000, 70, 1631 [Russ. J. Gen.
Chem. (Engl. Transl.), 2000, 70].
8. L. V. Ryapisova, Fosforilirovannye proizvodnye nesimmetrichꢀ
nogo dimetilgidrazina: sintez i issledovanie svoistv [Phosphoryꢀ
lated Derivatives of Asymmetric Dimethylhydrazine: Synthesis
and Study of the Properties], Ph.D. (Chem.) Thesis, Author´s
Abstract, Kazan, 1998, p. 15 (in Russian).
9. L. V. Ryapisova, L. B. Kashevarova, I. G. Shaikhiev, S. V.
Fridland, Zh. Obshch. Khim., 1997, 67, 2061 [Russ. J. Gen.
Chem. (Engl. Transl.), 1997, 67].
10. A. Heydari, A. Javidan, M. Schaffie, Tetrahedron Lett., 2001,
42, 8071.
11. A. Heydari, M. Mehrdad, M. Schaffie, M. Abdolrezaie,
R. Hajinassirei, Chem. Lett., 2002, 31, 1146.
12. A. Heydari, A. Arefi, Catal. Commun., 2007, 8, 1023.
13. C.ꢀL. Lien, C.ꢀT. Hsu, Int. J. Appl. Sci. Eng., 2008, 6, 11.
14. M. Chebib, G. A. R. Johnston, J. Med. Chem., 2000, 43,
1427.
15. N. W. Owens, C. Braun, F. Schweizer, J. Org. Chem., 2007,
72, 4635.
16. S. A. Mikhalenko, S. V. Barkanova, O. L. Lebedev, E. A.
Luk´yanets, Zh. Obshch. Khim., 1971, 41, 2735 [Russ. J. Gen.
Chem. (Engl. Transl.), 1971, 41].
Diethyl [(2ꢀacetylhydrazino)(phenyl)methyl]phosphonate (35)
was obtained from Nꢀbenzylideneacetohydrazide 23. The yield
1
was 35%. H NMR (CDCl3), δ: 1.21, 1.25 (both t, 6 H, 2 Me,
POEt, 3JH,H = 7.1 Hz); 1.83, 2.09 (both s, 3 H, Me); 3.95—4.07
(m, 4 H, OCH2); 4.50 (d, 1 H, CH; 2JH,P = 14.4 Hz); 5.27 (br.s,
NHNHAc); 7.30—7.37 (m, 3 H, arom.); 7.43—7.46 (m, 2 H,
arom.); 7.60 (br.s, NHNHAc). 31P NMR (CDCl3), δ: 20.46,
20.93. 13C NMR (CDCl3), δ: 16.11, 16.29 (both br.s, Me, POEt);
19.62, 20.89 (both s, C(O)CH3); 62.25, 62.54 (both d, CH,
1
1JC,P = 142.9 Hz, JC,P = 151.8 Hz); 62.75, 63.32 (both d,
POCH2, 2JC,P = 7.2 Hz, 2JC,P = 6.6 Hz); 128.31, 128.44, 128.94
3
2
(d, JC,P = 5.6 Hz); 133.90 (d, JC,P = 7.3 Hz) (Carom); 169.46,
175.36 (both s, C=O). IR, ν/cm–1: 1040, 1055 (P—O—C); 1260
(P=O); 1670 (C=O); 3270 (N—H). Found (%): C, 52.02; H,
7.10; N, 9.50. C13H21N2O4P. Calculated (%): C, 52.00; H, 7.05;
N, 9.33.
Diethyl (4ꢀhydrazinopiperidinꢀ4ꢀyl)phosphonate dihydrotriꢀ
fluoroacetate (36). αꢀHydrazino phosphonate 29 (1 mmol) was
dissolved in CH2Cl2 (5 mL). Then trifluoroacetic acid (5 mL)
was added and the reaction mixture was stirred at room temperꢀ

424
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Matveeva et al.
17. B. V. Ioffe, V. S. Stopskii, Z. I. Sergeeva, Zh. Org. Khim.,
1968, 4, 986 [J. Org. Chem. USSR (Engl. Transl.), 1968, 4].
18. R. H. Wiley, G. Irick, J. Org. Chem., 1959, 24, 1925.
19. G. S. Gol´din, Zh. Org. Khim., 1970, 6, 754 [J. Org. Chem.
USSR (Engl. Transl.), 1970, 6].
20. D. Todd, J. Am. Chem. Soc., 1949, 71, 1356.
21. H. McKennis, J. H. Weatherby, E. P. Dellis, Anal. Chem.,
1958, 30, 499.
25. M. Majchrzak, M. Bekhazi, I. TseꢀSheepy, J. Warkentin,
J. Org. Chem., 1989, 54, 1842.
26. A. Kurtz, C. Niemann, J. Org. Chem., 1961, 26, 1843.
27. T. V. Troepol´skaya, R. A. Sitdikov, Z. S. Titova, A. P. Stolꢀ
yarov, Yu. P. Kitaev, Izv. Akad. Nauk SSSR, Ser. Khim.,
1980, 1280 [Bull. Acad. Sci. USSR, Div. Chem. Sci.
(Engl. Transl.), 1980, 29].
28. M. Okimoto, T. Chiba, J. Org. Chem., 1990, 55, 1070.
22. G. Kaupp, U. Pogodda, J. Schmeyers, Chem. Ber., 1994,
127, 2249.
23. L. Spialter, D. O´Brien, G. Untereiner, W. Rush, J. Org.
Chem., 1965, 30, 3278.
24. R. McGirk, C. Cyr, W. Ellis, E. White, J. Org. Chem., 1974,
39, 3851.
Received July 16, 2009;
in revised form October 30, 2009