Phosphorylation of Betti Base with Bis(diethylamino)phosphoryl Chloride

Article abstract of DOI:10.1134/S1070363218110348

The reaction of bis(diethylamino)phosphoryl chloride with N-Boc-protected 1-(α-aminobenzyl)-2- naphthol (Betti base) proceeded via O-phosphorylation of the phenolic OH group to form the target product as trifluoroacetate salt. The latter reacted with O,O-diethyl thiophosphorylisothiocyanate to give thiourea bearing a chiral Betti base fragment.

Full text of DOI:10.1134/S1070363218110348

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 11, pp. 2453–2456. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © K.E. Metlushka, D.N. Sadkova, K.A. Nikitina, Z.R. Yamaleeva, K.A. Ivshin, O.N. Kataeva, V.A. Alfonsov, 2018, published in
Zhurnal Obshchei Khimii, 2018, Vol. 88, No. 11, pp. 1931–1934.
LETTERS
TO THE EDITOR
Dedicated to the 115th anniversary of B.A. Arbuzov’s birth
Phosphorylation of Betti Base
with Bis(diethylamino)phosphoryl Chloride
a
a
a
a
K. E. Metlushka , D. N. Sadkova , K. A. Nikitina , Z. R. Yamaleeva ,
a,b
a
a
K. A. Ivshin , O. N. Kataeva , and V. A. Alfonsov *
a
A.E. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences,
ul. Akademika Arbuzova 8, Kazan, Tatarstan, 420088 Russia
*
e-mail: alfonsov@yandex.ru
b
Butlerov Chemical Institute, Kazan (Volga Region) Federal University, Kazan, Tatarstan, Russia
Received June 21, 2018
Abstract—The reaction of bis(diethylamino)phosphoryl chloride with N-Boc-protected 1-(α-aminobenzyl)-2-
naphthol (Betti base) proceeded via O-phosphorylation of the phenolic OH group to form the target product as
trifluoroacetate salt. The latter reacted with O,O-diethyl thiophosphorylisothiocyanate to give thiourea bearing
a chiral Betti base fragment.
Keywords: Betti base, phosphorylation, thiourea
DOI: 10.1134/S1070363218110348
Chiral organophosphorus compounds are widely
O-phosphorylation, we carried out preliminary Boc-
protection of the amino group of the Betti base by
reacting with di-tert-butyl dicarbonate (Scheme 1). As
a result, the product 1 was obtained, which reacted
with tetraethyl diamidochlorophosphate in the
presence of potassium tert-butylate to form compound
used in modern asymmetric synthesis both as organo-
catalysts or chiral ligands, and as building blocks for
the production of biologically active substances [1–5].
In this regard, the search for methods for synthesizing
new specimens of this class of compounds is an urgent
task.
2 (δ = 13.68 ppm, Scheme 1). To remove the Boc-
P
protecting group, compound 2 without isolation was
treated with trifluoroacetic acid to form trifluoroacetate 3.
In continuation of our work on the study of the
possibility of phosphorylation of the Betti base and its
derivatives [6–9] with the aim of further application in
the asymmetric synthesis of phosphorus compounds,
we chose bis(diethylamino)phosphoryl chloride as the
phosphorylating agent. The introduction of additional
active groups into the chiral Betti base molecule
increases its functionality. In particular, the bis
It should be noted that the free base cannot be
isolated from the salt with trifluoroacetic acid even
when treated with an aqueous solution of sodium
carbonate. In the IR spectrum of 3, the absorption band
–1
at 1686 cm characteristic of the trifluoroacetate anion
and the broad band of the ammonium group at
(
diethylamino)phosphoryl group having pronounced
–1
2
933 cm are retained. The reason for the high
basic properties can provide the molecule with
additional activity when binding proton donors.
stability of compound 3 with respect to an aqueous
solution of sodium carbonate was made clear by
studying its structure by X-ray diffraction method
(Fig. 1). It can be seen from the obtained data that all
three protons of the ammonium group form strong
hydrogen bonds: two with trifluoroacetic acid anions,
and the third with strongly basic phosphoryl oxygen of
Direct phosphorylation of the Betti base is difficult
due to the presence of two active nucleophilic proton-
containing centers in the 1-(α-aminobenzyl)-2-
naphthol molecule that can compete in reaction with
electrophilic phosphorylating agents [7]. For selective
2
453

2
454
METLUSHKA et al.
Scheme 1.
NH2
OH +
NHBoc
OH
O
O
CH Cl , Δ
2
2
t-BuO
O
Ot-Bu
1
O
Cl P(NEt2)2
t-BuOK, C H6
6
.
NH CF COO
NHBoc
O
3
3
(
1) CF COOH, CH Cl
3 2 2
O
(
2) 0.5 M. Na CO3
2
P(NEt2)2
O
P(NEt2)2
O
3
2
the neighboring molecule. In this case, structure of the
hydrogen-bonded dimer is realized.
using IR, NMR spectroscopy, mass spectrometry and
X-ray diffraction data (Fig. 2).
1
31
The H, P NMR and mass spectrometry data confirm
In summary, we obtained new products of the Betti
base phosphorylation, promising polyfunctional poly-
dentate chiral derivatives.
also the proposed structure of compound 3.
It is interesting to note that for carrying out the
reaction of salt 3 with O,O-diethyl phosphorylisothio-
cyanate, it is not necessary to isolate the free base. The
reaction readily proceeded with trifluoroacetate 3 to
form compound 4, which is a double phosphorylated
thiourea containing a chiral Betti base fragment
tert-Butyl (2-hydroxynaphth-1-yl)(phenyl)methyl-
carbamate 1 was synthesized according to the method
described in [7].
[2-(Tetraethyldiamidophosphoryloxy)naphth-1-
(
Scheme 2). Structure of compound 4 was established
yl](phenyl)methylammonium trifluoroacetate (3). A
Fig. 1. A fragment of the crystal packing of compound 3. Intermolecular hydrogen bonds are marked by a dotted line.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

PHOSPHORYLATION OF BETTI BASE
2455
Scheme 2.
S
S
P(OEt)2
.
NH CF COO
S
HN
N
3
3
H
SCN P(OEt)2
O
O
P(NEt2)2
O
CH
3
CN
P(NEt2)2
O
3
4
mixture of 15 mL of anhydrous benzene, 0.6 g
1.72 mmol) of compound 1, and 0.21 g (1.89 mmol)
off, washed with cold aceto-nitrile, and dried in a
(
vacuum. Yield 0.32 g (69.8%), mp 164–166°С
–
1
of potassium t-butoxide was stirred for 30 min, and
then cooled to 5°C. A solution of 0.41 g (1.81 mmol)
of bis(diethylamino)phosphoryl chloride in 2 mL of
anhydrous benzene was added. The resulting mixture
was kept at room temperature in an argon atmosphere
for 24 h, then the precipitate was filtered off. The
solvent was removed at a reduced pressure. A mixture
of 3 mL of trifluoroacetic acid and 6 mL of methylene
chloride was added to the residue. After stirring for
(CH CN). IR spectrum, ν, cm : 1007 s (P–O–C ),
3
A
l
k
1026 s (P–O–C ), 1243 s (P=O), 1350 s (S=C–NH),
Alk
1546 s (S=C–NH), 1598 w (C=C ), 1625 w (C=C ),
Ar
Ar
1
3080 br (NH). Н NMR spectrum, δ, ppm: 0.78 t and
1.32 t (6Н, OCH CH , J = 7.1 Hz), 1.04 t and 1.08 t
(12Н, NCH CH , J = 7.1 Hz), 3.04–3.32 m (8Н,
3
2
3
НН
3
2
3
НН
NCH CH ), 3.85–3.93 m (2Н, OCH CH , H ), 4.11–
2
3
2
3
A
3
4.19 m (2Н, OCH CH , H ), 7.08 d (1Н, NH, J =
2
3
B
НP
13.4 Hz), 7.21–8.06 m (12Н, PhCH + Н ), 8.84 br. s
Ar
3
1
1
.5 h at room temperature, the volatiles were removed
at a reduced pressure. The residue was dissolved in
0 mL of methylene chloride, and 10 mL of 0.5 M.
(1Н, NH). P NMR spectrum, δ , ppm: 14.27, 56.83.
Mass spectrum (ESI ), m/z: 651.3 [M + H] , 1323.4
[2M + Na] . Found, %: С 55.52; Н 6.61; N 8.42; P
P
+
+
+
1
aqueous solution of sodium carbonate was added. The
resulting mixture was stirred for 1 h at room
temperature, then the organic layer was separated, and
the aqueous layer was extracted with methylene
chloride (2 × 5 mL). The organic layers were
combined and dried with Na SO . The solvent was
9.40; S 9.87. С Н N O P S . Calculated, %: 55.37; Н
6.81; N 8.61; P 9.52; S 9.85.
3
0
44
4
4 2 2
31
P NMR spectra were recorded on a Bruker
Avance-400 instrument (161.98 MHz), relative to the
1
external standard (85% H PO ). H NMR spectra were
3
4
2
4
recorded on
a
Bruker Avance-400 instrument
removed at a reduced pressure, and the residue was
crystallized from acetonitrile. Yield 0.64 g (67.4%),
(400.13 MHz) relative to the signals of residual protons
of CDCl . IR spectra were recorded on a Bruker
–
1
3
mp 198–199°C (CH CN). IR spectrum, ν, cm : 1225 s
3
Tensor 27 spectrometer from KBr pellets. Mass spec-
trometry was performed on an AmazonX instrument.
Melting points were measured on a Boetius melting
point microscope.
(
(
1
3
P=O), 1599 w (C=C ), 1628 w (C=C ), 1686 s
Ar Ar
+
1
C=O), 2933 br (NH ). Н NMR spectrum, δ, ppm:
3
3
.03 t and 1.07 t (12Н, NCH CH , J = 7.1 Hz), 2.88–
2 3 НН
.21 m (8Н, NCH CH ), 6.65 s (1Н, PhCH), 7.25–7.41
2
3
31
m (8Н, Н ), 7.84–8.01 m (3Н, Н ). P NMR
spectrum: δ 15.08 ppm. Mass spectrum (ESI ), m/z:
3
Ar
Ar
+
P
+
+
+
67.3 [M – NEt ] , 440.2 [M + H] , 879.5 [2M + H] .
2
Found, %: С 58.75; Н 6.56; N 7.40; P 5.43. С Н F N O P.
27
35
3
3
4
Calculated, %: С 58.58; Н 6.37; N 7.59; P 5.60.
1
-[(2-Tetraethyldiamidothiophosphatoxynaphth-
-yl)methyl]-3-(O,O-diethylthiophosphoryl)thiourea
4). To a solution of 0.39 g (0.7 mmol) of compound 3
1
(
in 12 mL of CH CN, a solution of 0.163 g (0.77 mmol)
3
of O,O-diethyl thiophosphorylisothio-cyanate in 3 mL
of CH CN was added at room temperature. The
3
mixture was stirred at room tem-perature for 4 h, and
then kept for 1 day at 10°C. The crystals were filtered
Fig. 2. General view of the molecule of compound 4 in the
crystal.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

2
456
METLUSHKA et al.
X-Ray diffraction study of the crystals of com-
pounds 3 and 4 was carried out on a Bruker AXS
CONFLICT OF INTERESTS
No conflict of interests was declared by the authors.
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2
1
3
7
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4
are triclinic
3
C H N O P S , 0.101 × 0.211 × 0.315 mm , M =
6
3
0
44
4
4 2 2
1
0.1134/S107036321603004X
50.75 g/mol, space group P-1, Z = 2, a = 8.6379(8) Å,
b = 11.6272(11) Å, c = 17.4633(17) Å, α = 79.662(2)°,
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3
β = 87.055(2)°, γ = 80.189(2)°, V = 1699.8(2) Å , d
=
calc
3
–1
1
.271 g/cm , μ = 0.290 mm , 25861 reflection were
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the range of θ from 1.80° to 28.00°, 8132 independent
9
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=
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2
0
.0444, wR = 0.1039. The maximum and minimum
3
residual electron density peaks are 0.665 and –0.352 e/Å .
1
1
1
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in Cambridge Crystallographic Data Center [CCDC
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1
849405 (3), 1849404 (4)].
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018