Phosphorylated aminoacetal in the synthesis of new acyclic, cyclic, and heterocyclic polyphenol structures

Article abstract of DOI:10.1002/hc.21153

New phosphorylated aminoacetal has been synthesized by the Kabachnik-Fields reaction; its reactivity has been studied in acid-catalyzed condensation with linear polyphenols (2-methylresorcinol, resorcinol, pyrogallol) and the Mannich reaction with macrocy

Full text of DOI:10.1002/hc.21153

Heteroatom Chemistry
Volume 25, Number 3, 2014
Phosphorylated Aminoacetal in the Synthesis
of New Acyclic, Cyclic, and Heterocyclic
Polyphenol Structures
Liliya I. Vagapova,1 Alexander R. Burilov,1 Julia K. Voronina,1
Victor V. Syakaev,1 Dilyara R. Sharafutdinova,1
Lyaysan R. Amirova,2 Michael A. Pudovik,1 Airat R. Garifzyanov,3
and Оleg G. Sinyashin1
1A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian
Academy of Sciences, Kazan 420088, Russia
2General Organic and Petrochemical Synthesis Department, Institute of Petroleum, Chemistry, and
Nanotechnology, Kazan National Research Technological University, Kazan 420015, Russia
3Analytical Chemistry Department, A. Butlerov Institute of Chemistry, Kazan (Volga Region)
Federal University, Kazan 420008, Russia
Received 10 January 2013; revised 12 March 2014
this article online at wileyonlinelibrary.com. DOI
ABSTRACT: New phosphorylated aminoacetal has
10.1002/hc.21153
been synthesized by the Kabachnik–Fields reaction; its
reactivity has been studied in acid-catalyzed conden-
sation with linear polyphenols (2-methylresorcinol,
resorcinol, pyrogallol) and the Mannich reaction
INTRODUCTION
with macrocyclic polyphenol (calix[4]resorcinol). It
has been determined for the first time that acid-
catalyzed reaction of phosphorus-containing acetal
with resorcinol and its derivatives in ethanol in
the presence of hydrochloric acid gives new phos-
phorylated piperazines in addition to the com-
pounds of diarylmethane series. Condensation of
macrocyclic polyphenol (calix[4]resorcinol) with
formaldehyde and N-((dihexylphosphoryl)methyl)-2,
2-dimethoxyethylamine (the Mannich reaction) has
resulted in novel tetrasubstituted calixarene contain-
ing aminophosphine oxide and acetal groups on the
It has been known that acetals are promising com-
pounds for the synthesis of both macro- and hete-
rocyclic structures. In particular, N-benzyl(hetaryl)
aminoacetals represent attractive precursors for the
synthesis of many five- to seven-membered hetero-
cycles and alkaloids [1–4], as well as diarylmethane
derivatives [5, 6] with a broad range of pharmaco-
logical activity.
We have shown earlier that condensation of
functionally substituted acetals with resorcinol and
its derivatives in acidic media is a convenient
method to prepare unique linear and cyclic polyphe-
nols, namely, P,N-containing calix[4]resorcinols [7,
8], derivatives of diarylmethane series [9–11] in-
cluding those on macrocyclic framework [12],
and imidazolidine-2-ones containing polyphenol
fragments [13]. It was determined that synthe-
sized calix[4]resorcinols can be utilized in micellar
ꢀC
“upper rim” of molecule.
2014 Wiley Periodi-
cals, Inc. Heteroatom Chem. 25:178–185, 2014; View
Correspondence to: Liliya I. Vagapova; e-mail: vagapovan@
mail.ru.
Contract grant sponsor: Russian Foundation for Basic Research
Contract grant number: 12-03-31138_mol_a, 13-03-97073.
2014 Wiley Periodicals, Inc.
ꢀC
178

Phosphorylated Aminoacetal in Synthesis of New Acyclic, Cyclic, and Heterocyclic Polyphenol Structures 179
O
P
O
+ HP
C6H6
-H2O
O
O
C6H13
C6H13
C6H13
C6H13
+CH2O
H2N
Me
Me
N
H
Me
O
O
Me
1
SCHEME 1 Synthesis of N-((dihexylphosphoryl)methyl)-2,2-dimethoxyethylamine 1.
R
R
catalysis [14, 15] and are able to complexation with
rare earth metal ions [16, 17] and extraction of car-
bon nanotubes [18]. Derivatives of diarylmethane se-
HO
OH
HO
OH
NH2
Cl
ries are of interest as polydentate ligands [19].
R
-2MeOH
-4MeOH
P O
C6H13
HO
2
OH
+
C6H13
It should be noted that the type of the products,
which are formed during acid-catalyzed reaction of
resorcinol and its derivatives with functionally sub-
stituted acetals, depends substantially on the struc-
ture of the latter, as well as experimental conditions.
We followed research in this direction study-
ing the properties of previously unknown acetal
containing the aminophosphine oxide fragment.
Aminophosphine oxide derivatives are used as al-
kali and rare metal extractants due to their ability
to complexation [20, 21]. A combination of several
functional groups in one molecule (acetal and sec-
ondary amino group) would allow the use of the
compounds of this type as a universal synthetic block
for the design of macrocyclic and linear polyphenols,
promising polydentate ligands containing the phos-
phine oxide fragment.
EtOH/HCl
(1)
2a-c
O
P
2, 3:R=Me (a), H(b), OH(c)
C6H13
OH
R
C6H13
OH
N
N
OH
C6H13
R
HO
P
O
C6H13
3a-c
SCHEME 2 Interaction of resorcinol and its derivatives with
N-((dihexylphosphoryl)methyl)-2,2-dimethoxyethylamine 1 in
acidic media.
However, there were no published data on the syn-
thesis of piperazine derivatives containing aryl sub-
stituents in addition to phosphine oxide fragments.
2,5-Bis(2, 4-dihydroxy-3-methylphenyl)-1, 4-(bis
(dihexylphosphorylmethyl))piperazine 3а was iso-
lated with the yield of 15% in the case of 2-methyl
resorcinol and the yield of N-[2,2-bis(2,4-dihydroxy-
3-methylphenyl)ethyl]-N-((dihexylphosphoryl)meth
yl)amine hydrochloride 2а was 60%.
A subsequent study of the reaction showed that
condensation of acetal 1 with resorcinol and pyro-
gallol in ethanol in the presence of concentrated hy-
drochloric acid at the (acetal-to-polyphenol = 1:2)
reagent ratio proceeds in analogy with that described
above for the formation of the derivatives of diaryl-
methane series 2b,c with the yields of 20% and 35%,
respectively, and tetrasubstituted piperazines 3b,c.
It should be noted that the latter are formed in trace
amounts and were detected only in the reaction mix-
ture by means of MALDI mass spectrometry.
With an aim to study the effect of reaction
conditions on the type, yield, and ratio of formed
products, we varied temperature (20–80оС), time
of experiment, as well as reagent ratio and types of
solvents and acids.
RESULTS AND DISCUSSION
Phosphorylated acetal 1 was synthesized accord-
ing to the Kabachnik–Fields reaction of aminoac-
etaldehyde dimethylacetal with paraform and di-
hexylphosphinous acid in benzene catalyzed by
p-toluenesulfonic acid with the yield of 91%
(Scheme 1).
The reaction of 2-methylresorcinol with N-((dihe
xylphosphoryl)methyl)-2,2-dimethoxy-ethylamine 1
in ethanol in the presence of concentrated hy-
drochloric acid yields two types of products. In
MALDI mass spectra of reaction mixture, there were
signals of N-[2,2-bis(2,4-dihydroxy-3-methylphenyl)
ethyl]-N-((dihexylphosphoryl)-methyl)amine hydro
chloride 2а, m/e = 520 ([M – HCl + H]+), and
also product of cyclization, 2,5-bis(2,4-dihydroxy-3-
methylphenyl)-1, 4-(bis(dihexylphosphorylmethyl))
piperazine 3а, m/e = 791 [M + H]+ (Scheme 2).
Treatment of reaction mass by acetone enables one
to isolate compounds 2а and 3а.
It was determined that temperature of the reac-
tion and an increase in time of experiment do not
influence substantially the ratio and yield of prod-
ucts 2а–с and 3а–с. On the other hand, the reagent
ratio was found to have a significant effect only on
the yield of compounds 2b and 2с.
The formation of compound 3а was unexpected,
but it is an interesting fact. Piperazine derivatives at-
tract the attention of researchers in organic synthesis
due to its pronounced biological activities [22, 23].
Heteroatom Chemistry DOI 10.1002/hc

180 Vagapova et al.
Condensation of polyphenols with acetal 1 at a
5:1 reagent ratio is followed by an increase in the
yields of compounds 2b and 2с up to 57% and 52%,
respectively.
The effect of solvents and catalysts on this re-
action is worth noting. For example, substitution of
Lewis acid (BF3·(OEt2)) for Brønsted acid (HCl) in
the reactions of resorcinol and 2-methylresorcinol
with aminoacetal 1 leads to uncontrolled forma-
tion of oligomers in ethanol; and conduction of this
reaction in a nonpolar solvent (chloroform) with
trifluoroacetic acid does not give the products of
condensation. There are unreacted polyphenol and
ammonium salt of compound 1 in the reaction
mixture.
Thus, optimal conditions for the synthesis of
derivatives of diarylmethane series 2а–с are as fol-
lows: conduction of the reaction in ethanol and hy-
drochloric acid at 5:1 reagent (polyphenol:acetal)
ratio and heating the reaction mixture for 1 h at
55–60оС. It should be noted that dropwise addition
of hydrochloric acid to the solution of aminophos-
phine oxide 1 and polyphenol in ethanol at 10оС is
desirable to avoid oligomerization.
FIGURE 1 Molecular structure of compound 3a.
center of inversion. Bond lengths, valence, and tor-
sion angles have the values, which are in the ranges
intrinsic for each type of bond. Configuration of
the phosphorus atom is tetrahedral, and O1P1C2,
O1P1C12, O1P1C18 angles are 114.77(2)º, 112.67(1)º,
and 110.95(1)º, respectively (Fig. 1).
The presence of phosphoryl and hydroxyl groups
results in the formation of classical hydrogen bond
between neighboring molecules in crystal; the dis-
tance from the hydrogen atom of the hydroxyl group
of one molecule to the oxygen atom of the phospho-
The structure and composition of products 2а–с
and 3а were confirmed by 1Н, 31Р, and 13С NMR spec-
troscopy; IR spectroscopy; mass spectrometry; ele-
mental analysis; and X-ray diffraction analysis (3а).
In 31Р NMR spectrum of compounds 2а–с, there
1
is one signal at 43–44 ppm. In Н NMR spectra of
˚
ryl group of another one corresponds to 2.73 A; and
compounds 2a–c, signals of methyl groups of hexyl
substituent at the phosphorus atom appear as a
triplet (0.85–0.87 ppm); methylene groups of hexyl
substituent as multiplets (1.26–1.42 ppm); methy-
lene groups of hexyl substituent at the phosphorus
atom as a multiplet (1.77 ppm); signals of methyl
groups as a singlet (for compound 2a, 1.99 ppm);
methylene groups bonded to phosphorus and ni-
trogen atoms as doublets (2.80 (СD3OD) and 3.28–
3.29 ppm (d6-DMSO)); methylene groups between
the nitrogen atom and the methine group as a dou-
blet (3.57–3.58 (d6-DMSO), 3.01 (СD3OD)); protons
of methine groups as a triplet (4.48, 4.82–4.99 ppm);
protons at ortho- (6.08–6.33 ppm) and meta- (6.39–
6.74 ppm) positions of aromatic nuclei as singlets;
protons of hydroxyl groups (8.45–8.94 ppm) and
protons of amino group (9.41 ppm) as broad sin-
glets. In IR spectra, absorption bands of Р=О (1205–
1207 cm−1), С=Сar (1606–1625 cm−1), and ОН
(3242–3249 cm−1) groups are detected.
angle O8H8···O1 is 172.3°. Two-dimensional layers
directed along the main diagonal of the parallelo-
gram of the unit cell are formed by these interactions
(Fig. 2).
In IR spectrum of 3а, absorption bands of Р=О
(1210 cm1), С=Сar (1604 cm−1), and ОН (3184,
3500 cm−1) groups are detected.
According to X-ray analysis, a molecule of com-
pound 3а in a crystal is in special position at the
FIGURE 2 Crystal packing of compound 3a.
Heteroatom Chemistry DOI 10.1002/hc

Phosphorylated Aminoacetal in Synthesis of New Acyclic, Cyclic, and Heterocyclic Polyphenol Structures 181
It should be noted that tetrasubstituted piper-
cle, as well as type of used solvents, various num-
bers of aminoalkyl groups can be introduced in the
calix[4]resorcinol molecule according to the Man-
nich reaction [27–29]. We demonstrated that varia-
tion of stoichiometric reagent ratios (from 1:1:1 to
1:5:5) in the reaction under study as well as a solvent
(ethanol/benzene, methanol) does not affect remark-
ably the synthetic result; compound 5 is exclusively
formed in all experiments; only its yield changed.
The most optimal experimental conditions,
which enable one to prepare macrocycle 5 with the
maximum yield, are ethanol/benzene medium, calix
[4]resorcinol-to-formaldehyde-to-aminophosphine
oxide 1 reagent ratio of 1:5:5, and room temperature.
The product 5 represents an oily substance; the
presence of aminophosphine oxide substituents in
macrocycle 5 considerably improves its solubility
both in polar (alcohols, DMSO, acetone) and non-
polar (benzene, chloroform, diethyl ether) solvents
compared to its precursor 4. Unfortunately, the at-
tempts to grow the crystal, which is suitable for X-
ray diffractometry and is required for the determi-
nation of the cavity size and geometry of functional
groups of macrocycle 5, were ineffective.
azine 3а was isolated by us as free amine. This was
achieved by drying compound 3а under vacuum of
oil pump at 6 × 10−2 mmHg (0.06 Torr) for 3 h at t =
40оС. Preparation of diarylmethane derivatives 2а–с
with free amino group for subsequent participation
in complexation was of certain interest. Long drying
of these compounds under vacuum (0.06 Torr) also
results in the destruction of salt structure and forma-
tion of free bases, which, however, have extremely
poor solubility in organic solvents, thus complicat-
ing their subsequent application. Therefore, with
an aim to retain salt form, solvent removal from
products 2а–с was realized under mild conditions
(15 Torr, 30°C).
Following our studies, we chose calix[4]
resorcinol 4 as polyphenol to synthesize a macro-
cyclic polydentate ligand containing aminophos-
phine oxide fragments. It should be noted that these
macromolecules are obtained at acid-catalyzed con-
densation of aldehydes (acetals) with resorcinols;
therein orthopositions between hydroxyl groups of
resorcinol rings remain free for subsequent func-
tionalization [24].
We have shown earlier that these positions are
active in electrophilic substitution reactions with
methylene carbocations (the Mannich reaction, ben-
zylation, and so on) [25,26].
The presence of secondary amino group
in the phosphine oxide molecule 1 allows its
use for modification of “upper rim” of calix[4]
resorcinol by the Mannich reaction. Condensa-
tion of calix[4]resorcinol 4 with formaldehyde and
aminophosphine oxide 1 at a 1:5:5 reagent ratio
in an ethanol/benzene mixture at room temper-
ature yielded new tetrasubstituted macrocycle 5
(Scheme 3).
The structure of compound 5 was assigned by
NMR (1H, 31P, 13C) and IR spectroscopy; compo-
sition was proved according to elemental analysis
data. In 31P NMR spectrum of compound 5, there
is one signal at 46 ppm. In 1H NMR spectrum of
compound 5, there is no signal at 6.2 ppm corre-
sponding to orthoproton of resorcinol rings in the
calix[4]resorcinol matrix; this indicates the forma-
tion of a product of tetrasubstitution of macrocycle.
Compound 5 was synthesized from the rccc-
isomer of calix[4]resorcinol 4, which, according to
the literature data, does not transform into another
isomer even at high temperature [30–32]. In our
case, the reaction proceeds at room temperature and
this transformation is even less possible. It may be
concluded that at ambient temperature, compound
It is known from published data that, depend-
ing on the reagent ratio, structure of amines, length
of alkyl substituent on the “lower rim” of macrocy-
R
O
R
R
P
P
MeO
R
O
R
OMe
OMe
OMe
R
P
O
N
OMe
OMe
O
R
OMe
R
P
N
N
N
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
MeO
OH
OH
+4 CH2O +4 (1)
-4H2O
4
5
R= C6H13
SCHEME 3 Synthesis of calix[4]resorcinol 5, containing aminophosphine oxide and acetal groups.
Heteroatom Chemistry DOI 10.1002/hc

182 Vagapova et al.
1
of the synthesized compounds toward soft metals
ions.
5 adopts an rccc-configuration. The analysis of H
NMR spectra of compounds 4 and 5 shows that
four methine protons that link aromatic fragments
and four protons at four position of resorcinol rings
are equivalent and the position of these signals in
spectra almost does not change after chemical func-
tionalization of macrocycle 4 and corresponds to
(4.28 ppm (4, 5)) the protons of methine groups and
(7.20 (4) and 7.09 ppm (5)) the protons of aromatic
rings. In 1H NMR spectrum of compound 5, the
protons of methine groups linking methoxy groups
(4.31 ppm); methoxy groups (3.19 ppm); protons
of methylene groups bonded to the nitrogen atom
and methine group (2.86 ppm), phosphorus atom
(3.38 ppm), or resorcinol ring (3.82 ppm) also ap-
pear as one set of signals; this indicates on the high
symmetry of obtained macrocycle. The character of
absorption bands of hydroxyl groups in IR spectra of
compounds 4 (2256 cm−1) and 5 (3300 cm−1) almost
does not differ and is recorded in the range, which is
intrinsic for hydrogen-bonded hydroxyl groups. The
combination of the mentioned data confirms that,
despite relatively bulky substituents in orthoposition
of aromatic rings of calix[4]resorcinol 5, in CDCl3
solution, the spectrum corresponding to averaged
“cone” conformation is observed.
It is known from the published data that the for-
mation of zwitterionic structures in aminomethy-
lated calix[4]resorcinols is possible due to in-
tramolecular hydrogen bonds between hydroxy
groups and nitrogen atoms [33–35]. The analysis of
spectral data for compound 5 showed that 13С NMR
signals of aromatic carbon atoms that are linked to
hydroxyl groups are equivalent and appear in spec-
trum as singlet (151.1 ppm); in addition, there are no
absorption bands in the range of 2500–2600 cm−1
in IR spectrum of macrocycle 5; these facts indi-
cate the absence of an zwitterionic structures in our
case [35].
It was shown earlier that calix[4]arenes con-
taining aminophosphonate fragments on the up-
per rim of molecule are effective and selective
amino acid transfer agents compared with their lin-
ear counterparts [36] and lipophilic derivatives of
aminophosphine oxides participate both in mem-
brane transport of amino acids and as metal ion
extractants from acidic media [20, 21, 37]. It is an-
ticipated that the presence of lipophilic cavity with a
long alkyl chain and four thermally and hydrolyt-
ically stable aminophosphine oxide fragments in
synthesized calix[4]resorcinol would increase the
binding efficiency and selectivity with organic and
inorganic substrates compared with their linear
counterparts and unsubstituted calix[4]resorcinol.
We are currently exploring the extraction ability
EXPERIMENTAL
Spectroscopic Measurements
NMR experiments were performed on a Bruker
AVANCE-600 spectrometer (Karlsruhe, Germany) at
303 K equipped by 5 mm broadband probehead
working at 600.1 MHz in H and 150.9 MHz in 13C
1
experiments. Chemical shifts in 1H and 13C spec-
tra were reported relative to the solvent as inter-
nal standard (CDCl3, CD3OD, d6-DMSO). 31Р NMR
spectra were recorded on a Bruker AVANCE II-
400 (Karlsruhe, Germany, 161.9 MHz for 31P), and
chemical shifts were reported relative 85% H3PO4
as external standard. Assignment was accomplished
by means of COSY, 2D H-13C HSQC, and 2D H-
13C HMBC experiments. IR spectra were recorded
on a Bruker Vector-22 fourier spectrometer (Karl-
sruhe, Germany) in the wave number range from
4000 to 400 cm−1. MALDI mass spectra were ob-
tained on an ULTRAFLEX III mass spectrometer
(Bruker Daltonic GmbH, Bremen, Germany). Mea-
surements were conducted with the use of plastic
and metal plates. 2,5-Dihydroxybenzoic acid (2,5-
DHB) was used as matrix.
1
1
X-Ray Measurements
Crystal data for 3a: C22H38NO3P, M = 395.42;
molecule in crystal is in special position at the centre
of inversion. colorless crystal 0.1 × 0.1 × 0.2 mm,
triclinic, space group P-1, Z = 2, a = 11.035(2),
˚
a = 10.427(6) b = 10.692(6), c = 12.020(7) A, α =
111.858(7), β = 104.361(7), γ = 101.083(8), V =
3
1142.9(11) A , ρcalc = 1.134 g cm−3, μ = 0.138 mm–
˚
˚
1, λ = 0.71073 A, T = 150 K, Bruker Smart Apex II
CCD diffractometer, 7043 reflections collected ( h,
k, l), 4165 independent and 1828 observed re-
flections [I ≥ 2 σ(I)], 234 refined parameters, R =
0.0996, wR2 = 0.1753, max. Residual electron den-
sity 0.590(–0.400) eA−3. CCDC 973062.
˚
Synthesis
The starting calix[4]resorcinol 4 was prepared as de-
scribed in [30].
N-((Dihexylphosphoryl)methyl)-2,2-dimethoxyet
hylamine, 1. Mixture of dihexylphosphinous acid
(1 g, 4.58 mmol), aminoacetaldehyde dimethylac-
etal (0.48 g, 4.58 mmol), and paraformaldehyde
(0.137 g, 4.58 mmol) was heated under reflux
Heteroatom Chemistry DOI 10.1002/hc

Phosphorylated Aminoacetal in Synthesis of New Acyclic, Cyclic, and Heterocyclic Polyphenol Structures 183
9.1 (br. s., 5H, OH, NH). 13С NMR (d6-DMSO),
δ = 9.2 (CH3Car), 13.8 (СH3CH2), 20.5, 21.8, 29.9,
in the flask equipped with Dean–Stark adapter
and reflux condenser for 3 h in the presence of
p-toluenesulfonic acid (0.01 g). After completion
of the reaction, potassium carbonate (0.12 g) was
added to the reaction mixture and heated under
reflux for additional 10 min; mixture was cooled
and washed three times with water. Organic layer
was separated and solvent was removed.
30.6 (CH3(CH2)4), 27.4 (CH2P, 1J
= 66 Hz),
PC
1
34.2 (CHCH2), 45.4 (PCH2NH, J
= 59 Hz), 51.6
PC
(CH2CH), 106.6 (Car), 111.4 (CarCH3), 118.5 (CarCH),
124.8 (Car), 153.1 (CarOH), 154.8 (CarOH). 31P NMR
(d6-DMSO), δ = 43.98 (s). MS (MALDI), m/z: = 520
[M – HCl + H]+, 542 [M – HCl + Na]+, 558 [M – HCl
+ K]+.
There is an oily product in residue. Yield: 1.4 g
(91%) compound 1, nD20 1.47. Anal. calcd for C17H38
NO3P: C, 60.87; H, 11.42; N, 4.18; P, 9.23. Found: C,
60.35; H, 11.56; N, 4.27; P, 9.13. IR (ν, cm−1): 1127
(COC), 1242 (P=O), 3338 (NH). 31Р NMR (CDCl3),
N-[2,2-Bis(2,4-dihydroxyphenyl)ethyl]-N-((dihex
ylphosphoryl)methyl)amine Hydrochloride, 2b. We
synthesized 2b in analogy with previous study
from 0.82 g (7.5 mmol) of resorcinol, 0.5 g
(1.5 mmol) of aminophosphine oxide in ethanol
(6 mL) and hydrochloric acid (1.5 mL). Residue was
precipitated from methanol to diethyl ether.
1
3
δ = 47.33 (s). Н NMR (CDCl3): δ = 0.79 (t, JHH
=
7.10 Hz, 6H, CH2CH3), 1.21 (br. s., 8H, СH2), 1.29
(m, 4H, CH2), 1.48 (m, 4H, CH2), 1.62 (m, 4H, CH2P),
2.69 (br. s., 2H, NCH2), 2.83 (m, 2JPH = 12.10 Hz, 2H,
3
PCH2), 3.26 (s, 6Н, OCH3), 4.32 (t, JHH = 5.40 Hz,
Yield: 0.45 g (57%); mp 85–86°C. Anal. calcd for
C27H43NO5ClP: С, 61.41; Н, 8.21; Р, 5.87; N, 2.65;
Cl, 6.71. Found: С, 61.38; Н, 8.36; P, 5.68; N, 2.64;
Cl, 6.76. IR (ν, cm−1): 1208 (P=O), 1606 (C=C),
2626 (NH+), 3260 (OH). 31P NMR (d3-CD3OD): δ =
1Н, CH). MS (MALDI): m/z = 374 [M + K]+.
Reaction of 2-Methylresorcinol, Resorcinol, and
Pyrogallol with Aminophosphine Oxide, 1
1
3
43.37(s). H NMR (d3-CD3OD), δ = 0.85 (t, JHH
=
To the solution of 2-methylresorcinol (1.64 g,
13.24 mmol) and aminophosphine oxide 1 (1.21 g,
3.61 mmol) in EtOH (6 mL) in a three-necked flask
equipped with a condenser, magnetic stirrer, ther-
mometer, and dropping funnel, hydrochloric acid (3
mL) was added dropwise at 10°С. The reaction mix-
ture was stirred at room temperature for 2 h and
further heated from 55 to 60оС. After 1 h of heat-
ing, solvent was removed under the vacuum of water
pump, residue was washed with dry acetone, dried
under the vacuum of oil pump (0.06 Torr, 3 h, 40°C),
and 0.22 g (15.4%) compound 3а was obtained.
Solvent was removed from acetone filtrate un-
der the vacuum of water pump; residue was precip-
itated from ethanol to diethyl ether and dried un-
der the vacuum of water pump (15 Torr, 30°C) to a
constant weight. 1.2 g (60%) of compound 2а was
obtained.
6.70 Hz, 6Н, CH2CH3), 1.29 (br. s., 12H, CH2), 1.38
(m, 4H, CH2), 1.57 (m, 4H, CH2), 2.80 (d, 2JPH = 8.1
Hz, 2H, PCH2N), 3.01 (d, 3JHH = 6.6 Hz, 2Н, NHCH2),
4.48 (t, 3JHH = 6.60 Hz, 1H, CH), 6.08 (d, 3JHH = 8.37
Hz, 2H, CHar), 6.23 (s, 2H, CHar), 6.70 (d, 3JHH = 8.37
Hz, 2H, CHar), 8.88, 8.94 (br. s., 4H, OH), 9.19 (br. s.,
1H, NH). 13С NMR (d6-DMSO), δ = 14.8 (СH3CH2),
21.5, 22.8, 30.7, 31.9 (CH3(CH2)4), 27.9 (CH2P, 1JPC
=
66.0 Hz), 35.4 (CHCH2), 43.1 (PCH2NH, 1JPC = 59.0
Hz), 51.6 (CH2CH), 103.6 (CHar), 107.1 (CarH), 118.1
(CarCH), 130.2 (CHar), 156.6 (CarOH), 157.9 (CarOH).
MS (MALDI), m/z = 491 [M – HCl + K]+.
N-[2,2-Bis(2,3,4-trihydroxyphenyl)ethyl]-N-
((dihexylphosphoryl)methyl)amine
Hydrochloride,
2c. We synthesized 2c from 0.5 g (1.5 mmol)
aminophosphine oxide 1 and 0.95 g (7.5 mmol) of
pyrogallol in 6 mL ethanol and 2 mL hydrochlo-
ric acid in analogy with previous study, residue
was reprecipitated from acetone to diethyl ether.
Yield 0.43 g (52%); mp 128–130°C. Anal. calcd for
C27H43NO7ClP: С, 57.90; Н, 7.74; Р, 5.53; N, 2.50;
Cl, 6.33. Found: С, 57.81; Н, 7.82; P, 5.53; N, 2.51;
Cl, 6.37. IR (ν, cm−1): 1207 (P=O), 1608 (C=C),
2624 (NH+), 3265 (OH). 31P NMR (d6-DMSO): δ =
43.71(s). 1H NMR (d6-DMSO): δ = 0.86 (t, 3JHH = 6.7
Hz, 6Н, CH2CH3), 1.27 (br. s., 8H, CH2), 1.33 (m, 4H
CH2), 1.42 (m, 4H, CH2), 1.80 (m, 4H, PCH2CH2),
N-[2,2-Bis(2,4-dihydroxy-3-methylphenyl)ethyl]-
N-((dihexylphosphoryl)methyl)amine Hydrochloride,
2a. Yield 1.2 g (60%); mp 124–125°C. Anal. calcd
for C29H47NO5ClP: С, 62.63; Н, 8.52; Р, 5.57; N, 2.52;
Cl, 6.38. Found: С, 62.58; Н, 8.46; P, 5.58; N, 2.54;
Cl, 6.36. IR (ν, cm−1): 1205 (P=O), 1606 (C=C),
2620 (NH+), 3249(OH). 1H NMR (d6-DMSO), δ 0.87
3
(t, JHH = 6.7 Hz, 6Н, CH3), 1.26–1.34 (br. s., 12H,
CH2), 1.42 (m, 4H, CH2), 1.77 (m, 4H, CH2P), 1.99
2
(s, 6H, CH3), 3.28 (d, JPH = 5.7 Hz, 2H, PCH2N),
3
3
3
3.57 (d, JHH = 6.9 Hz, 2Н, CH2N), 4.99 (t, JHH
=
3.29 (br. s., 2H, PCH2), 3.56 (d, JHH = 7.70 Hz, 2Н,
3
3
7.7 Hz, 1H, CH), 6.33 (d, JHH = 8.4 Hz, 2H,
NHCH2), 4.82 (t, JHH = 7.70 Hz, 1H, CH), 6.23 (d,
3
3
CHar), 6.74 (d, JHH = 8.4 Hz, 2H, CHar), 8.4, 8.9,
3JHH = 8.41 Hz, 2H, CHar), 6.39 (d, JHH = 8.41 Hz,
Heteroatom Chemistry DOI 10.1002/hc

184 Vagapova et al.
2H, CHar), 8.45, 8.62 (br. s., 4H, OH). MS (MALDI),
m/z = 524 [M – HCl + H]+, 546 [M – HCl + K]+.
(NCH2CH), 103.8 (CH(OCH3)2), 110.1 (CarCH2),
122.6 (CarCH), 124.1 (CHar), 151.1 (CarOH).
2,5-Bis(2,4-dihydroxy-3-methylphenyl)-1,4-(bis
REFERENCES
(dihexylphosphorylmethyl))-piperazine,
3a. Yield
0.22 g (15%); mp 225–226°C. Anal. calcd for C44H76
N2O6P2: С, 66.81; Н, 9.68; Р, 7.83; N, 3.54. Found: С,
66.58; Н, 9.88; P, 7.59; N, 3.56. IR (ν, cm−1): 1210
(P=O), 1604 (C=C), 3184, 3150 (OH). 31Р NMR
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(d6-DMSO), δ = 45.55(s). H NMR (d6-DMSO), δ =
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6Н, CH3), 1.17–1.22 (br. s., 24H, CH2), 1.55 (br. s.,
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PC
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59.0 Hz), 57.5 (CH2CH), 107.6 (MeCHar), 111.8
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4,6,10,12,16,18,22,24-Octahydroxy-5,11,17,23-
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(CHCH2N), 52.8 (NCH2P, JPC = 78.0 Hz), 52.9
3
(CH2Car, JPC = 5.6 Hz), 54.3 (CH(OCH3)2), 54.6
Heteroatom Chemistry DOI 10.1002/hc

Phosphorylated Aminoacetal in Synthesis of New Acyclic, Cyclic, and Heterocyclic Polyphenol Structures 185
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