Preparation of the library of fluorescent aromatic aminophosphonate phenyl and benzyl esters

Article abstract of DOI:10.1080/10426507.2015.1094658

Classical hydrophosphonylation of Schiff bases have been used for the preparation of library of diphenyl and dibenzyl aromatic aminomethylphosphonates N-substituted with aromatic moieties. The reaction, although being capricious provided the desired products in satisfactory yields. When using harsh reaction conditions conversion of diphenyl esters into monophenyl ones was observed. On the other hand, the use of more delicate conditions resulted in lack of hydrophosphonylation. The fluorescence studies revealed that the obtained library could be used for the construction of diagnostic microarrays.

Full text of DOI:10.1080/10426507.2015.1094658

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Preparation of the library of fluorescent aromatic
aminophosphonate phenyl and benzyl esters
Michał Górny vel Górniak & Paweł Kafarski
To cite this article: Michał Górny vel Górniak & Paweł Kafarski (2016) Preparation of the library
of fluorescent aromatic aminophosphonate phenyl and benzyl esters, Phosphorus, Sulfur, and
Silicon and the Related Elements, 191:3, 511-519, DOI: 10.1080/10426507.2015.1094658
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1094658
View supplementary material
Accepted author version posted online: 13
Jan 2016.
Submit your article to this journal
Article views: 20
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gpss20
Download by: [University of California, San Diego]
Date: 30 March 2016, At: 01:04

PHOSPHORUS, SULFUR, AND SILICON
, VOL. , NO. , –
http://dx.doi.org/./..
Preparation of the library of fluorescent aromatic aminophosphonate phenyl and
benzyl esters
Michał Górny vel Górniak and Paweł Kafarski
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland
ABSTRACT
ARTICLE HISTORY
Received  August 
Accepted  September 
Classical hydrophosphonylation of Schiff bases have been used for the preparation of library of diphenyl
and dibenzyl aromatic aminomethylphosphonates N-substituted with aromatic moieties. The reaction,
although being capricious provided the desired products in satisfactory yields. When using harsh reaction
conditions conversion of diphenyl esters into monophenyl ones was observed. On the other hand, the use
of more delicate conditions resulted in lack of hydrophosphonylation. The fluorescence studies revealed
that the obtained library could be used for the construction of diagnostic microarrays.
KEYWORDS
Aminophosphonate library;
fluorescence;
hydrophosphonylation
GRAPHICAL ABSTRACT
library the simple and efficient chemical procedures resulting
in a wide variety of structurally related compounds are indis-
pensable. In this paper, we have exploited addition of diphenyl
and dibenzyl phosphites to Schiff bases obtained from aromatic
aldehydes and aromatic amines as a mean to construct such a
library of fluorescent inhibitors.
Introduction
Diphenyl aminophosphonates and their short peptides are well
recognized from their ability to inhibit serine proteinases by
phosphonylating their active-site serine hydroxyl moiety.1–3 It
is also well acknowledged that tumor tissues are characterized
by overproduction of many proteases with some of them being
marker enzymes for cancerogenesis.4–6 Thus, the enzymatic
cocktails of healthy and cancer tissues differ significantly from
each other.
Results and discussion
We speculate that the use of aminophosphonate libraries Synthesis
of potential inhibitors of the proteinases (and most likely
The addition of phosphites to Schiff bases is one of the oldest
phosphatases) might be useful in construction of diagnostic
microarrays facilitating diagnosis based on biopsy. Indeed,
libraries of short peptides have been already considered as
potential diagnostic tools.7–10 In order to construct such a
and most commonly used procedure for aminophosphonate
synthesis.11–13 It also seems to be a trivial and simple reaction.
However, the synthesis of structurally overcrowded aminophos-
phonates starting from aromatic aldehydes, aromatic amines,
CONTACT Paweł Kafarski
pawel.kafarski@pwr.edu.pl
Wyspian´skiego , - Wrocław, Poland.
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzez˙e
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
In memoriam of Professor Reinhard Schmutzler.
Supplemental data for this article can be accessed on the publisher’s website at http://dx.doi.org/./..
©  Taylor & Francis Group, LLC

512
M. G. VEL GÓRNIAK AND P. KAFARSKI
Scheme . Outline of the synthesis.
and diphenyl or dibenzyl phosphites (Scheme 1) appeared to be
We speculate that this effect results from high packing of the
not an easy task. Dibenzyl and diphenyl phosphites substantially resulting diphenyl aminophosphonate molecules, which might
differ in nucleophilicity and thus are good models for studies force removal of phenol from the phosphonate moiety. On
on applicability of this reaction.14
the other hand, a similar reaction using dibenzyl phosphite
The first step of the synthesis was a choice and production of gave dibenzyl aminophosphonates in good to excellent yields
appropriate Schiff bases 1. They were obtained in moderate to (Table 1).
good yields by standard procedure. Unfortunately, none of the
As shown in Table 1 diphenyl and dibenzyl phosphonates
efforts to hydrophosphonylate bases 1za–1zg gave satisfactory (compounds 2) were successfully obtained by a slight modi-
results. In these cases, products were obtained in low yields as fication of the reaction conditions (reaction in THF in atmo-
components of complex reaction mixtures.
sphere of inert gas). The desired compounds were obtained
Quite surprisingly, addition of diphenyl phosphites to the with satisfactory yields (Table 1); however, their purification
Schiff bases derived from naphth-1-yl-methylamine carried caused quite substantial problems. Sterically overcrowded Schiff
out in elevated temperature in acetonitrile provided mostly bases obtained from o-nitrobenzaldehyde and anthracene-9-
monoesters 3 instead of the expected diphenyl esters 2 carboxyladehyde did not react with both phosphites in these
(Scheme 1; Table 1). The only exception was the addition of this conditions even after prolonged heating.
phosphite to Schiff base obtained from p-nitrobenzaldehyde,
Finally, addition of tris(trimethylsilyl) phosphites, which
which resulted in diphenyl ester 2Axc. The reaction of the Schiff were synthesized in situ, followed by delicate hydrolysis of
base obtained from 1-naphthylcarboxyaldehyde afforded the trimethylsilyl esters afforded corresponding aminophospho-
mixture of both mono (compound 2Axd) and diphenyl (com- nic acids 4 in moderate, albeit satisfactory, yields (Scheme 2;
pound 3Axd) esters.
Table 2). These compounds, however, appeared to be very
weakly soluble in any solvent (DMSO, alkaline and acidic water,
methanol).
Table . Diphenyl and dibenzyl N-substituted aminobenzylphosphonates.
Fluorescence
Compound R = Ph
Yield [%]
Compound R = CHPh
Yield [%]
A typical fluorescence (emission) measurement for selected
aminophosphonate esters dissolved in dimethyl sulfoxide
(DMSO) was determined using excitation wavelengths fixed at
254, 316, 346, and 366 nm. The best results have been obtained
at 366 nm (Figure 1a). Generally, strong quenching of DMSO
fluorescence by these compounds was observed.
3Axa








3Axb
2Axc
2Bxc
2Bxd
2Bxe
2Bxf
2Bxg





2Axd + 3Axd
3Axe
3Axf
3Axg
2Aya
Also fluorescence excitation measurements have been per-
formed by fixing the detection wavelengths at 360, 400, 440, and
480 nm. The most striking results were obtained for 400 nm
(Figure 1b). These studies indicated that the obtained libraries
could be useful for construction of fluorescent diagnostic chips.
2Byb
2Byc
2Byd
2Bye
2Byg





2Ayc
2Ayd



PHOSPHORUS, SULFUR, AND SILICON
513
Scheme . Synthesis of N-substituted aminomethanephosphonic acids.
Chemistry, Wroclaw University of Technology using Waters
LCT Premier XE mass spectrometer (methods of ionization ESI
(electrospray ionization)).
Purities of the products were determined by both thin layer
chromatography (Silica Gel 60 with fluorescent indicator) and
by high-performance liquid chromatography (HPLC; Waters
600 apparatus equipped with Waters 2489 UV-Vis detector,
columns: SUPELCO Discovery Bio Wide pore C8 and Waters
Spherisorb ODS2 analyticaL; column).
UV and fluorescence determinations have been performed
using 5 mM DMSO solutions of aminophosphonates at 25°C
using Gemini XSP apparatus and SofMax Pro programme. The
Supplemental Materials contains sample chromatographic and
spectroscopic data for representative compounds (Figures S1–
S12).
Experimental
All solvents and reagents were purchased from commercial sup-
pliers, were of analytical grade, and were used without further
purification. Unless otherwise specified solvents were removed
with a rotary evaporator. Infrared spectra were measured on a
1600 FT-IR Perkin-Elmer spectrometer. 1H and 31P NMR exper-
iments were performed on a Bruker Avance TM DRX oper-
ating at 300.13 MHz (1H), 121.51 MHz (31P) and on Bruker
Avance II Ultrashield Plus 600.58 MHz (1H), 243.12 MHz
(31P) while 13C NMR studies on Bruker Avance II Ultrashield
Plus 600.58 MHz (1H) spectrometer operating 151.016 MHz
(13C) and Bruker Ultrashield 400.13 MHz (1H) spectrome-
ter operating 100.61 MHz (13C). Measurements were made in
CDCl3 (99.8 at.%D), DMSOd6 (99.8 at.%D), and MeOD (99.8%
at.%D) solutions at temperature 300 K, all solvents were supplied
by ARMAR AG (Dottingen, Switzerland). Chemical shifts are
reported in parts per million relative to tetramethylsilane (TMS)
or 85% H3PO4 used as external standards, while coupling con-
stants are reported in Hertz. Melting points were determined
on an Electrothermal 9200 apparatus and are reported uncor-
rected. Electrospray mass spectra were recorded at Faculty of
Synthesis of Schiff bases (1)—general procedure
Amine (0.03 mole) was dissolved in chloroform (30 mL). The
solution was heated to 40°C and the solution of appropriate
aldehyde (0.03 mole) in the same solvent (15 mL) was added
dropwise for 1 h with stirring. The reaction was continued
at this temperature for additional 8 h and left overnight at
room temperature. Then the solution was dried over anhy-
drous MgSO4 and the solvent was evaporated in vacuum. Evap-
oration of the chloroform resulted in crude product, which
was crystallized either from methanol or methanol–chloroform
mixture.
Table . N-substituted aminobenzylphosphonates.
Compound
Yield [%]
Compound
Yield [%]
4xa
4xb
4xc
4xd
4xe
4xf






4xg
4ya
4yc
4yc
4yf





Physicochemical data for Schiff bases are given in supple-
mentary material.

514
M. G. VEL GÓRNIAK AND P. KAFARSKI
Figure . Fluorescence spectra of chosen aminophosphonates: (a) emission spectra; (b) excitation spectra.
Addition of diphenyl phosphite to Schiff bases obtained
from naphth-1-ylmethylamine
heated to 80°C and the reaction carried out for additional 4–20 h
until precipitation of a white solid was observed. The product
precipitated completely after cooling to room temperature.
Filtering and washing with small portions of acetonitrile
provided the desired aminophosphonates of satisfactory
purity.
Schiff base 1× (0.005 mole) was dissolved in hot (40°C) ace-
tonitrile (20 mL). When the solution became clear, diphenyl
phosphite (0.005 mole) was added dropwise and the mixture was

PHOSPHORUS, SULFUR, AND SILICON
515
Phenyl N-(naphth--ylmethyl)amino-o-nitrobenzylphospho- DMSO) δ 18.17 (s, diester), 6.98 (s, monoester); HRMS (ESI-
nate (3Axa)
TOF) m/z: [MH]+ Calcd. for C34H28NO3P: 530.1885, Found:
Phenyl N-(naphth-1-ylmethyl)amino-o-nitrobenzylphosphon- 530.1863, while for monoester: C34H28NO3P: 454.1572, Found:
ate (3Axa) was obtained as a cream color solid with a melt- 454.1589.
ing point of 133–134°C. 31P NMR (162 MHz, DMSO) δ 5.03;
1H NMR (400 MHz, DMSO) δ 8.05 (d, J = 8.2 Hz, 2H), 7.88
(d, J = 8.2 Hz, 2H), 7.83 (d, J = 7.3 Hz, 1H), 7.61 (t, J =
Phenyl N-(naphth--ylmethyl)naphth--ylaminomethylphos-
8.2 Hz, 2H), 7.49–7.34 (m, 4H), 7.08 (t, J = 7.9 Hz, 2H),
phonate (3Axe)
6.92–6.81 (m, 3H), 5.20 (d, J = 16.4 Hz, 1H, CHP), 4.65 and
4.95 (AB system, J = 13.4, 2H, CH2Ar); 13C NMR (101 MHz,
DMSO) δ 153.02, 152.94, 148.92, 148.87, 133.69, 133.33, 132.05,
130.67, 130.00, 129.32, 129.12, 128.94, 126.97, 126.41, 125.61,
125.17, 124.13, 122.91, 120.46, 120.42, 54,48 (d, J = 13.3,
CP), 47.63 (CH2); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for
C24H22N2O5P: 449.1266, Found: 449.1280.
Phenyl N-(naphth-1-ylmethyl)naphth-2-ylaminomethylphos-
phonate (3Axe) was obtained as a white solid, m.p. 224–226°C.
1
31P NMR (122 MHz, DMSO): δ 5.00; H NMR (601 MHz,
DMSO) δ 8.12 (d, J = 8.4 Hz, 1H), 8.05–7.72 (m, 5H), 7.72–7.55
(m, 2H), 8.55–7.29 (m, 4H), 7.27–7.02 (m, 2H), 6.93 (m, 3H),
5.00 (d, J = 13.6 Hz, 1H, CHP), 4.46 and 4.62 (AB system, J
= 14.3 Hz, 2H, CH2); 13C NMR (101 MHz, DMSO) δ 153.53,
133.63, 132.96, 132.82, 132.62, 132.07, 130.02, 129.87, 129.51,
129.25, 128.91, 128.74, 128.16, 127.91, 127.65, 126.93, 126.60,
126.44, 125.61, 124.37, 122.59, 120.73, 60.88 (d, J = 133.2 Hz,
CP), 47.43 (CH2); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for
C28H24NO3P: 454.1572, Found: 454.1583.
Phenyl N-(naphth--ylmethyl)amino-m-nitrobenzylphospho-
nate (3Axb)
Phenyl N-(naphth-1-ylmethyl)amino-m-nitrobenzylphospho-
nate (3Axb) was obtained as a white solid with a melting point
1
of 223–225°C. 31P NMR (162 MHz, DMSO) δ 4.97; H NMR
(400 MHz, DMSO) δ 8.33 (s, 1H), 8.14 (d, J = 7.9 Hz, 1H),
8.01 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 9.2 Hz, 2H), 7.78 (d, J
= 7.5 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.50–7.30 (m, 4H),
7.07 (t, J = 7.9 Hz, 2H), 6.95–6.77 (m, 3H), 5.05 (d, CHP, J
= 13.4 Hz, 1H), 4.54 and 4.59 (AB system, J = 14.5 Hz, 2H).
13C NMR (101 MHz, DMSO) δ 153.36, 153.29, 147.64, 137.25,
136.68, 133.58, 132.04, 130.22, 129.96, 129.56, 129.30, 128.89,
128.62, 126.99, 126.44, 125.59, 124.45, 124.37, 122.77, 120.48,
60.12 (d, J = 131.3, CP), 47.86 (CH2); HRMS (ESI-TOF) m/z:
[MH]+. Calcd. for C24H22N2O5P: 449.1266, Found: 449.1273.
Phenyl N-(naphth--ylmethyl)anthracen--ylaminomethyl-
phosphonate (3Axf)
Phenyl N-(naphth-1-ylmethyl)anthracen-9-ylaminomethylph-
osphonate (3Axf) was obtained as a yellow solid, m.p. 270–
272°C. 31P NMR (122 MHz, DMSO): δ 1.34; 1H NMR
(601 MHz, DMSO) δ 8.26–8.17 (m, H) 8.14 (d, J = 8.3 Hz, 1H),
8.04 (dd, J = 15.1 Hz, J = 8.1 Hz, 2H), 7.74 (d, J = 7.0 Hz,
1H), 7.66 8.04 (ddd, J = 11.5 Hz, J = 8.7 Hz, J = 5.3 Hz, 5H),
7.55–7.44 (m, 4H), 7.33–7.23 (m, 4H), 7.20 (dd, J = 19.6 Hz,
J = 11.6 Hz), 6.99 (d, J = 8.1 Hz, 2H), 6.99 (d, J = 18.4 Hz,
1H, CHP), 5.13–4.97 (m, 2H, CH2Ar); 13C NMR (101 MHz,
DMSO) δ 157.77, 153.01, 150.68, 133.68, 132.14, 131.62, 131.39,
130.78, 130.26, 129.92, 129.31, 128.92, 127.03, 126.63, 126.26,
125.58, 125.50, 125.11, 124.97, 124.07, 123.38, 122.95, 121.01,
120.97, 120.58, 119.20, 115.65, 55.13 (d, J = 133.3 Hz, CP), 48.65
(CH2); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for C32H26NO3P:
504.1729, Found: 504.1732.
Diphenyl N-(naphth--ylmethyl)amino-p-nitrobenzylphos-
phonate (2Axc)
Diphenyl N-(naphth-1-ylmethyl)amino-p-nitrobenzylphosph-
onate (2Axc) was obtained as a white solid with a melting
point of 220°C. 31P NMR (162 MHz, DMSO) δ 16.78; 1H NMR
(400 MHz, DMSO) δ 8.20 (d, J = 8.4 Hz, 1H), 8.16–8.08 (m,
1H), 8.04 (d, J = 8.7 Hz, 1H), 7.88–7.81 (m, 3H), 7.63 (d, J =
7.5 Hz, 1H), 7.57–7.50 (m, 1H), 7.48–7.27 (m, 4H), 7.24–7.14
(m, 3H), 7.14–7.03 (m, 3H), 6.99–6.79 (m, 3H), 4.75 (d, CHP,
J = 23.6 Hz, 1H), 3.94 and 4.21 (AB system, J = 13.6 Hz, 2H,
CH2Ar); 13C NMR (101 MHz, DMSO) δ 150.54, 150.26, 147.64,
135.21, 133.85, 133.65, 132.02, 131.93, 130.64, 130.23, 130.14,
129.55, 129.12, 128.88, 128.79, 128.13, 127.01, 126.90, 126.12,
125.74, 125.63, 124.63, 124.41, 123.86, 123.11, 122.61, 120.91,
120.64, 58.52 (-CH2-), 49.04 (J = 123.5 Hz, CP); HRMS (ESI-
TOF) m/z: [MH]+ Calcd. for C30H26N2O5P: 525.1580, Found:
525.1573.
Phenyl N-(naphth--ylmethyl)phenathren--ylaminomethyl-
phosphonate (3Axg)
Phenyl N-(naphth-1-ylmethyl)phenathren-9-ylaminomethyl-
phosphonate (3Axg) was obtained as a white solid, m.p. 183–
185°C. 31P NMR (162 MHz, DMSO) δ 6.05; 1H NMR (400 MHz,
DMSO) δ 8.75 (dd, J = 21.1, J = 8.3 Hz, 2H), 8.42 (s, 1H), 8.10
(d, J = 8.3 Hz, 1H), 7.84 (d, J = 8.1 Hz, 2H), 7.75 (d, J = 7.5 Hz,
2H), 7.64 (d, J = 7.0 Hz, 1H), 7.58 (t, J = 7.5 Hz, 2H), 7.47 (t,
J = 7.5 Hz, 1H), 7.40 (t, J = 7.5 Hz, 2H), 7.34–7.21 (m, 2H),
7.01 (t, J = 7.5 Hz, 2H), 6.90–6.78 (m, 3H), 5.24 (d, J = 14.6 Hz,
1H, CHP), 4.77 and 5.12 (AB system, J = 12.7 Hz, 2H, CH2);
13C NMR (101 MHz, DMSO) δ 153.37, 153.30, 133.60, 132.09,
131.17, 130.56, 130.30, 130.19, 129.82, 129.20, 128.92, 128.81,
Diphenyl and phenyl N-(naphth--ylmethyl)naphth--
ylaminomethylphosphonates (2Axd+3Axd)
Diphenyl and phenyl N-(naphth-1-ylmethyl)naphth-1- 127.40, 127.25, 126.81, 126.34, 125.52, 124.84, 123.56, 123.09,
ylaminomethylphosphonates (2Axd+3Axd) were obtained in a 122.68, 120.69, 55,66 (d, J = 127.3 Hz, CP), 47.75 (CH2); HRMS
molar ratio of 64:36 (diester to monoester) as determined ten- (ESI-TOF) m/z: [MH]+ Calcd. for C32H26NO3P: 504.1729,
tatively by integration of 31P NMR signals. 31P NMR (162 MHz, Found: 504.1716.

516
M. G. VEL GÓRNIAK AND P. KAFARSKI
Addition of diphenyl and dibenzyl phosphites to Schiff
bases—general procedure
system, J = 12.0, J = 7.6 Hz, 2H, POCH2), 4.49 (d, J = 21.7 Hz,
1H, CHP), 3.87 and 4.14 (AB system, J = 13.2 Hz, 2H, CH2Ar);
13C NMR (101 MHz, DMSO) δ 137.04, 136.98, 136.84, 136.78,
135.61, 134.36, 133.86, 133.24, 133.09, 131.95, 128.83, 128.76,
128.61, 128.49, 128.36, 128.17, 128.02, 127.98, 127.72, 126.79,
126.70, 126.51, 126.32, 126.08, 125.79, 124.51, 68.07 (d, J =
6.7 Hz, POCH2), 67.35 (d, J = 6.8 Hz, POCH2), 59.75 (d, J
= 153.1 Hz, CHP), 48.99 (d, J = 17.8 Hz, CH2Ar); HRMS
(ESI-TOF) m/z: [MH]+ Calcd. for C40H34NO3P: 558.2198,
Found: 558.2207.
Schiff base (0.005 mole) was dissolved in THF (20 mL) and
warmed to 40°C. The mixture was stirred in an atmosphere
of argon until all the substrate dissolved. Then the appropri-
ate phosphite (0.005 mole) was added dropwise during 1 h. The
stirring was continued for additional 15 h and then the solvents
were removed in vacuo yielding dense oils. The products were
purified by Silica Gel 60 (230–400 mesh, ASTM) column chro-
matography using ethyl acetate-hexane (3:1 v/v) or ethyl acetate-
hexane-chloroform (3:1:6 v/v) mixtures as eluents.
Dibenzyl N-(naphth--ylmethyl)anthracen--ylaminomethyl-
phosphonate (2Bxf)
Dibenzyl N-(naphth--ylmethyl)amino-p-nitrobenzylphos-
phonate (2Bxc)
Dibenzyl N-(naphth-1-ylmethyl)anthracen-9-ylaminomethyl-
phosphonate (2Bxf) was obtained as a yellow oil. 31P NMR
Dibenzyl N-(naphth-1-ylmethyl)amino-p-nitrobenzylphosph-
1
(122 MHz, DMSO): δ 25.94; H NMR (601 MHz, DMSO) δ
onate (2Bxc) was obtained as a yellow solid, m.p. 136–138 °C.
9.31 (d, J = 8.2 Hz, 1H), 8.14 (dd, J = 19.8 Hz, J = 8.2 Hz,
3H), 7.97 (d, J = 8.5 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.76
(d, J = 8.1 Hz, 1H), 7.60–6.96 (m, 16H), 6.69 (d, J = 8.3 Hz,
2H), 5.89 (dd, J = 24.4 Hz, J = 5.8 Hz, 1H, CHP), 5.01 (d, J =
7.8 Hz, 2H, POCH2), 4.38 and 4.62 (ABX system, J = 12.1, J
= 7.5 Hz, 2H, POCH2), 4.11–3.86 (m, 2H, CH2Ar); 13C NMR
(101 MHz, DMSO) δ 170.78, 136.96, 136.90, 136.40, 136.34,
135.48, 133.77, 131.86, 131.46, 131.39, 131.37, 130.69, 130.64,
129.72, 129.30, 129.04, 128.80, 128.73, 128.56, 128.41, 128.23,
128.13, 128.11, 127.43, 127.06, 126.87, 126.19, 126.04, 125.63,
125.28, 124.53, 124.06, 67.95 (d, J = 6.9 Hz, POCH2), 67.25 (d,
J = 6.8 Hz, POCH2), 55.78 (d, J = 154.8 Hz, CHP), 50.01 (d, J
= 16.2 Hz, CH2Ar); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for
C40H34NO3P: 608.2355, Found: 608.2349.
1
31P NMR (122 MHz, DMSO): δ 23.4; H NMR (400 MHz,
DMSO) δ 8.11 (d, J = 8.4 Hz, 2H), 8.04 (d, J = 7.9 Hz, 1H),
7.87–7.80 (m, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.67 (dd, J = 8.8,
2.0 Hz, 2H), 7.46–7.09 (m, 12H), 7.06–7.00 (m, 2H), 4.91 (d, J
= 7.8 Hz, 2H, POCH2), 4.74 and 4.81 (ABX system, J = 12.1,
J = 8.1 Hz, 2H, POCH2), 4.47 (d, J = 22.7 Hz, 1H, CHP),
3.86 and 4.09 (AB system, J = 13.6 Hz, 2H, CH2Ar); 13C NMR
(101 MHz, DMSO) δ 147.41, 147.37, 145.16, 136.85, 136.79,
136.70, 136.64, 135.38, 133.83, 131.87, 130.36, 130.30, 128.81,
128.78, 128.69, 128.57, 128.49, 128.05, 127.91, 126.85, 126.35,
126.08, 125.75, 124.47, 123.67, 68.31 (d, J = 6.8 Hz, POCH2),
67.59 (d, J = 6.9 Hz, POCH2), 59.34 (d, J = 151.7 Hz, CHP),
49.28 (CH2Ar), 49.11 (CH2Ar); HRMS (ESI-TOF) m/z: [MH]+
Calcd. for C32H30N2O5P: 553.1892, Found: 553.1888.
Dibenzyl N-(naphth--ylmethyl)phenathren--ylaminome-
thylphosphonate (2Bxg)
Dibenzyl N-(naphth--ylmethyl)naphth--ylaminomethyl-
phosphonate (2Bxd)
Dibenzyl N-(naphth-1-ylmethyl)phenathren-9-ylaminometh-
ylphosphonate (2Bxg) was obtained as a yellow oil. 31P NMR
(162 MHz, DMSO) δ 25.24, 22.17; 1H NMR (400 MHz, DMSO)
δ 8.85–8.77 (m, 2H), 8.15–8.05 (m, 2H), 7.95–7,81 (m, 1H),
7.82 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.69–7.49
(m, 6H), 7.43–7.37 (m, 1H), 7.36–7.05 (m, 10H), 7.00 (t, J =
7.4 Hz, 1H), 6.78 (d, J = 7.4 Hz, 1H), 5.19 (d, J = 21.1 Hz,
1H, CPH), 5.02–4.88 (m, 2H, POCH2), 4.77–4.48 (m, 2H,
POCH2), 3.94 and 4.20 (AB system, J = 13.2 Hz, 2H, CH2Ar);
13C NMR (101 MHz, DMSO) δ 169.24, 142.98, 137.03, 136.96,
136.57, 135.67, 133.85, 132.00, 129.03, 128.92, 128.79, 128.73,
128.68, 128.66, 128.55, 128.48, 128.34, 128.24, 128.10, 127.95,
127.88, 127.83, 127.61, 127.52, 127.00, 126.85, 126.29, 126.08,
125.70, 124.70, 68.15 (d, J = 6.7 Hz, POCH2), 67.33 (d, J =
6.8 Hz, POCH2), 63.32 (s, CH2Ar), 48.93 (d, J = 127.8 Hz,
CHP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for C40H34NO3P:
608.2355, Found: 608.2284.
Dibenzyl N-(naphth-1-ylmethyl)naphth-1-ylaminomethylph-
osphonate (2Bxd) was obtained as a cream color solid, m.p.
1
108–109°C. 31P NMR (122 MHz, DMSO): δ 24.85; H NMR
(601 MHz, DMSO) δ 8.22–7.78 (m, 7H), 7.71–7.06 (m, 15H),
6.92–6.74 (m, 2H), 5.30 (d, J = 21.7 Hz, 1H, CHP), 4.98 (d, J
= 7.1 Hz, 2H, POCH2), 4.43 and 4.70 (ABX system, J = 12.1, J
= 7.4 Hz, 2H, POCH2), 3.86 and 4.12 (AB system, J = 12.3 Hz,
1H, CH2Ar); 13C NMR (101 MHz, DMSO) δ 137.05, 136.99,
136.67, 136.61, 135.66, 133.85, 132.89, 132.35, 131.99, 129.05,
128.79, 128.74, 128.52, 128.46, 128.25, 128.08, 127.96, 127.51,
126.91, 126.49, 126.28, 126.08, 125.89, 125.69, 124.68, 68.10 (d,
J = 6.7 Hz, POCH2), 67.26 (d, J = 6.8 Hz, POCH2), 51.08 (d,
J = 268.0 Hz, CHP), 49.14 (d, J = 17.8 Hz, CH2Ar); HRMS
(ESI-TOF) m/z: [MH]+ Calcd. for C36H32NO3P: 558.2198,
Found: 558.2207.
Dibenzyl N-(naphth--ylmethyl)naphth--ylaminomethyl-
phosphonate (2Bxe)
Dibenzyl N-(naphth-1-ylmethyl)naphth-2-ylaminomethylph- Diphenyl N-(naphth--yl)amino-o-nitrobenzylphosphonate
osphonate (2Bxe) was obtained as a white solid, m.p. 137°C. (2Aya)
1
31P NMR (122 MHz, DMSO): δ 24.63; H NMR (601 MHz, Diphenyl N-(naphth-1-yl)amino-o-nitrobenzylphosphonate
DMSO) δ 8.14 (d, J = 8.2 Hz, 1H), 8.05–7.79 (m, 6H), 7.71 (d, J (2Aya) was obtained as a yellow solid, m.p. 142–145°C. 31P
= 8.7 Hz, 1H), 7.59–7.34 (m, 6H), 7.34–7.11 (m, 8H), 7.11–6.98 NMR (243 MHz, DMSO) δ 13.49; 1H NMR (601 MHz, DMSO)
(m, 2H), 4.99 (d, J = 7.1 Hz, 2H, POCH2), 4.66 and 4.77 (ABX δ 8.34 (d, J = 7.0 Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H), 8.13 (d,

PHOSPHORUS, SULFUR, AND SILICON
517
J = 8.0 Hz, 1H), 7.83 (d, J = 5.8 Hz, 1H), 7.77 (t, J = 7.5 Hz, (m, 11H), 6.66 (d, J = 7.5 Hz, 1H), 6.58–6.52 (m, 1H), 5.73
1H), 7.64 (t, J = 7.6 Hz, 1H), 7.53 (d, J = 6.0 Hz, 2H), 7.36–7.28 (dd, J = 25.6, J = 9.2 Hz, 1H, CHP), 5.16 (d, J = 8.0 Hz, 2H,
(m, 4H), 7.24 (t, J = 7.4 Hz, 1H), 7.22–7.13 (m, 2H), 7.07 POCH2), 5.07–4.94 (m, 2H, POCH2); 13C NMR (151 MHz,
(d, J = 7.5 Hz, 2H), 6.97–6.91 (m, 2H), 6.75 (d, J = 7.5 Hz, DMSO) δ 148.25, 139.71, 136.82, 136.78, 136.60, 135.35, 134.41,
1H), 6.62 (d, J = 7.4 Hz, 1H), 6.57 (dd, J = 27.4, J = 10.0 Hz, 130.10, 128.90, 128.82, 128.77, 128.68, 128.65, 128.51, 128.48,
1H, CHP); 13C NMR (151 MHz, MeOD) δ 158.60, 151.27, 128.45, 128.20, 128.06, 128.04, 126.65, 126.38, 125.11, 124.38,
150.87, 150.81, 150.28, 142.92, 142.82, 135.33, 135.27, 131.36, 123.62, 123.15, 122.41, 118.64, 107.08, 68.47 (d, J = 6.9 Hz,
131.15, 130.81, 130.65, 129.23, 127.53, 127.45, 126.90, 126.02, POCH2), 68.04 (d, J = 6.8 Hz, POCH2), 54.70 (d, J = 151.7 Hz,
125.64, 123.76, 121.65, 121.23, 121.20, 120.45, 120.08, 116.50, CP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for C31H27N2O5P:
108.02, 68.31, 52.08 (d, J = 158.5 Hz, CP); HRMS (ESI-TOF) 539.1736, Found: 539.1735.
m/z: [MH]+ Calcd. for C27H22N2O5P: 511.1423, Found: 511.
1434.
Dibenzyl N-(naphth--ylmethyl)amino-p-nitrobenzylphos-
phonate (2Byc)
Diphenyl N-(naphth--yl)amino-p-nitrobenzylphosphonate
(2Ayc)
Dibenzyl N-(naphth-1-ylmethyl)amino-p-nitrobenzylphosph-
onate (2Byc) was obtained as a brownish oil. 31P NMR
1
Diphenyl N-(naphth-1-yl)amino-p-nitrobenzylphosphonate (243 MHz, DMSO) δ 21.91; H NMR (601 MHz, DMSO) δ
(2Ayc) was obtained as a yellow solid, m.p. 116–117°C. 31P 8.24 (d, J = 8.3 Hz, 1H), 8.17 (d, J = 8.2 Hz, 2H), 7.95 (d, J
NMR (243 MHz, DMSO) δ 14.38; 1H NMR (601 MHz, DMSO) = 8.6 Hz, 2H), 7.83–7.78 (m, 1H), 7.53–7.49 (m, 2H), 7.43–
δ 8.36–8.32 (m, 1H), 8.29 (d, J = 8.3 Hz, 2H), 8.19 (d, J = 7.21 (m, 11H), 7.17 (t, J = 7.8 Hz, 1H), 6.59 (d, J = 7.6 Hz,
8.5 Hz, 2H), 7.84–7.79 (m, 1H), 7.53–7.48 (m, 2H), 7.38–7.31 1H), 6.41 (t, J = 7.6 Hz, 1H), 5.69 (dd, J = 26.0, J = 8.9 Hz,
(m, 4H), 7.28 (d, J = 8.2 Hz, 1H), 7.25–7.18 (m, 3H), 7.15 (d, 1H, CHP), 5.15 (d, J = 8.2 Hz, 2H, POCH2), 5.03–4.96 (m, 2H,
J = 8.1 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.82 (m, 1H), 6.76 POCH2); 13C NMR (151 MHz, MeOD) δ 148.32, 145.99, 135.21,
(d, J = 7.4 Hz, 1H), 6.09 (dd, J = 27.3, 10.0 Hz, 1H, CHP); 130.74, 130.71, 129.81, 129.71, 129.66, 129.61, 129.52, 129.48,
13C NMR (151 MHz, DMSO) δ 150.66, 150.60, 150.35, 150.28, 129.32, 129.28, 129.17, 129.07, 128.97, 128.87, 127.70, 127.41,
147.81, 144.27, 142.17, 142.07, 134.46, 130.45, 130.29, 129.84, 127.21, 126.01, 125.13, 124.53, 122.98, 119.51, 107.92, 69.37 (d,
128.40, 126.60, 125.88, 125.83, 125.07, 124.68, 123.91, 122.81, J = 6.8 Hz, POCH2), 68.99 (d, J = 6.8 Hz, POCH2), 55.92 (d,
120.99, 120.97, 120.79, 119.27, 119.11, 115.70, 107.57, 55.67 (d, J = 150.0 Hz, CHP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for
J = 155.4 Hz, CP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for C31H27N2O5P: 539.1736, Found: 539.1735.
C30H25N2O5P: C27H22N2O5P: 511.1423, Found: 511.1438.
Dibenzyl N-(naphth--yl)naphth--ylmethylaminophos-
Diphenyl N-(naphth--yl)naphth--ylaminomethylphos-
phonate (2Byd)
phonate (2Ayd)
Dibenzyl N-(naphth-1-yl)naphth-1-ylmethylaminophospho-
Diphenyl N-(naphth-1-yl)naphth-1-ylaminomethylphospho- nate (2Byd) was obtained as a cream color solid, m.p. 137–
nate (2Ayd) was obtained as a brown solid, m.p. 139–144°C. 139°C. 31P NMR (243 MHz, DMSO) δ 23.25; 1H NMR
31P NMR (243 MHz, DMSO) δ 15.55; H NMR (601 MHz, (601 MHz, DMSO) δ 8.54 (d, J = 8.3 Hz, 1H), 8.24 (d, J =
1
DMSO) δ 8.35 (d, J = 8.1 Hz, 1H), 8.22 (d, J = 4.7 Hz, 8.1 Hz, 1H), 8.00 (d, J = 7.8 Hz, 2H), 7.91 (t, J = 10.9 Hz, 1H),
1H), 8.01 (d, J = 8.2 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.80 7.79 (d, J = 7.8 Hz, 1H), 7.63–7.57 (m, 2H), 7.55–7.45 (m, 3H),
(d, J = 7.5 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.60 (t, J = 7.36–7.27 (m, 5H), 7.24 (t, J = 7.1 Hz, 1H), 7.19 (t, J = 8.3 Hz,
7.5 Hz, 1H), 7.56–7.48 (m, 3H), 7.33 (t, J = 7.5 Hz, 2H), 3H), 7.06 (t, J = 7.9 Hz, 1H), 6.95 (d, J = 7.6 Hz, 2H), 6.42
7.25–7.09 (m, 8H), 6.82–6.76 (m, 1H), 6.74 (d, J = 7.9 Hz, (d, J = 6.5 Hz, 2H), 6.13 (dd, J = 24.5, j = 8.5 Hz, 1H, CHP),
2H), 6.58 (d, J = 7.6 Hz, 1H), 6.51 (dd, J = 25.8, 9.5 Hz, 5.17 (d, J = 8.32, 2H, POCH2), 4.59 and 4.91 (ABX system, J =
1H, CHP); 13C NMR (151 MHz, DMSO) δ 150.55 (dd, J = 12.8, J = 7.4 Hz, 2H, POCH2); 13C NMR (151 MHz, DMSO) δ
67.0, 9.9 Hz), 142.36, 142.26, 134.41, 133.84, 132.00, 131.83, 142.20, 142.11, 136.94, 136.90, 136.48, 136.44, 134.35, 133.87,
130.24, 130.18, 129.85, 129.34, 129.26, 128.42, 127.17, 126.75, 132.82, 131.83, 131.79, 129.24, 128.84, 128.66, 128.56, 128.50,
126.43, 126.38, 125.93, 125.75, 125.61, 125.13, 124.65, 124.07, 128.22, 128.06, 127.84, 126.95, 126.65, 126.38, 126.24, 126.01,
122.63, 121.12, 121.10, 120.49, 120.47, 119.27, 118.87, 115.71, 125.86, 125.27, 124.23, 124.15, 121.87, 118.38, 106.66, 68.38 (d,
107.19, 65.40, 51.82 (d, J = 159.3 Hz, CP); HRMS (ESI-TOF) J = 6.9 Hz, POCH2), 67.98 (d, J = 6.6 Hz, POCH2), 51.45 (d,
m/z: [MH]+ Calcd. for C33H26NO3P: 516.1729, Found: 516. J = 152.6 Hz, CP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for
1740.
C35H30NO3P: 544.2042, Found: 544.2048.
Dibenzyl N-(naphth--yl)amino-m-nitrobenzylphosphonate
Dibenzyl N-(naphth--yl)naphth--ylmethylaminophos-
(2Byb)
phonate (2Bye)
Dibenzyl N-(naphth-1-yl)amino-m-nitrobenzylphosphonate Dibenzyl N-(naphth-1-yl)naphth-2-ylmethylaminophospho-
(2Byb) was obtained as a brownish oil. 31P NMR (243 MHz, nate (2Bye) was obtained as a brownish solid, m.p. 133–136°C.
1
1
DMSO) δ 22.23; H NMR (601 MHz, DMSO) δ 8.62 (s, 1H), 31P NMR (243 MHz, DMSO) δ 23.24; H NMR (601 MHz,
8.28 (d, J = 7.8 Hz, 1H), 8.18–8.12 (m, 2H), 7.80 (d, J = 7.9 Hz, DMSO) δ 8.27 (d, J = 7.7 Hz, 1H), 8.21 (s, 1H), 7.90 (d, J
1H), 7.63 (t, J = 7.9 Hz, 1H), 7.53–7.49 (m, 2H), 7.43–7.15 = 7.2 Hz, 2H), 7.88–7.82 (m, 2H), 7.80 (d, J = 7.3 Hz, 1H),

518
M. G. VEL GÓRNIAK AND P. KAFARSKI
7.55–7.48 (m, 4H), 7.43–7.14 (m, 11H), 6.69 (d, J = 7.3 Hz, 1H), N-(Naphth--ylmethyl)amino-o-nitrobenzylphosphonic acid
6.41–6.34 (m, 1H), 5.60 (dd, J = 24.9, j = 8.0 Hz, 1H, CHP), (4xa)
5.17 (d, J = 7.7 Hz, 2H, POCH2), 4.88 and 5.02 (ABX system, N-(Naphth-1-ylmethyl)amino-o-nitrobenzylphosphonic acid
J = 12.6 Hz, J = 7.8 Hz; 2H, POCH2); 13C NMR (151 MHz, (4xa) was obtained as a white solid, m.p. 255°C. 31P NMR
MeOD) δ 143.21, 143.12, 137.78, 137.74, 137.55, 137.51, 135.34, (162 MHz, DMSO) δ 15.41; NMR (601 MHz, DMSO) δ 8.35
135.20, 134.02, 133.85, 129.82, 129.72, 129.65, 129.55, 129.46, (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.07–7.97 (m, 1H), 7.69–7.55
129.39, 129.35, 129.18, 129.06, 129.02, 128.95, 128.86, 128.80, (m, 2H), 5.02 (d, J = 20.2 Hz, 1H, CHP), 4.56 (s, 2H, CH2);
128.37, 128.32, 127.54, 127.49, 127.35, 127.15, 126.01, 125.13, 13C NMR (101 MHz, DMSO) δ 133.66, 131.08, 130.28, 129.61,
122.83, 119.20, 107.93, 69.15 (d, J = 6.7 Hz, POCH2), 68.79 129.12, 27.78, 127.22, 126.74, 125.82, 123.93, 120.20, 78.49
(d, J = 6.8 Hz, POCH2), 56.44 (d, J = 151.3 Hz, CP); HRMS (CH2), CP overshadowed by DMSO; HRMS (ESI-TOF) m/z:
(ESI-TOF) m/z: [MH]+ Calcd. for C35H30NO3P: 544.2042, [MH]− Calcd. for C18H17N2O5P: 371.0797, Found: 371.0841.
Found: 544.2048.
N-(Naphth--ylmethyl)amino-m-nitrobenzylphosphonic acid
(4xb)
N-(Naphth-1-ylmethyl)amino-m-nitrobenzylphosphonic acid
Dibenzyl N-(naphth--yl)phenathren--ylaminomethylphos- (4xb) was obtained as a white solid, m.p. 215°C. 31P NMR
phonate (2Byg)
(243 MHz, DMSO) δ 10.52 1H NMR (601 MHz, DMSO) δ 8.49
Dibenzyl N-(naphth-1-yl)phenathren-9-ylaminomethylphos- (d, J = 1.2 Hz, 1H), 8.22 (d, J = 8.0 Hz, 2H), 8.00 (d, J = 7.9 Hz,
phonate (2Byg) was obtained as a white solid; m.p. 121°C. 31
P
2H), 7.93 (t, J = 10.5 Hz, 1H), 7.72 (d, J = 7.0 Hz, 1H), 7.68 (t,
NMR (122 MHz, DMSO): δ 25.94; 1H NMR (601 MHz, DMSO) J = 8.0 Hz, 1H), 7.64–7.58 (m, 2H), 7.55 (t, J = 7.7 Hz, 1H),
δ 8.94 (d, J = 8.2 Hz, 1H), 8.84 (d, J = 8.4 Hz, 1H), 8.62 (d, J 5.05 and 5.12 (AB system, J = 14.8 Hz, 2H, CH2), 4.67 (d, J =
= 8.0 Hz, 1H), 8.38 (d, J = 2.4 Hz, 1H), 8.31 (d, J = 8.4 Hz, 13.4 Hz, 1H, CHP); HRMS (ESI-TOF) m/z: [MH]− Calcd. for
1H), 7.86 (d, J = 7.9 Hz, 1H), 7.82–7.72 (m, 3H), 7.68 (t, J = C18H17N2O5P: 371.0797 Found: 371.0795.
7.6 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.56 (t, J = 7.5 Hz, 1H),
7.51 (t, J = 7.4 Hz, 1H), 7.34 (d, J = 7.0 Hz, 2H), 7.30–7.25
N-(Naphth--ylmethyl)amino-p-nitrobenzylphosphonic acid
(4xc)
(m, 3H), 7.23–7.16 (m, 2H), 7.13 (t, J = 7.2 Hz, 2H), 7.05 (t,
J = 7.8 Hz, 1H), 6.95 (d, J = 7.5 Hz, 2H), 6.56 (t, J = 7.6 Hz,
N-(Naphth-1-ylmethyl)amino-p-nitrobenzylphosphonic acid
1H), 6.44 (d, J = 7.6 Hz, 1H), 6.15 (dd, J = 24.4, 8.5 Hz, 1H,
(4xc) was obtained as a white solid, m.p. 184–185°C. 31P NMR
CHP), 5.25–5.13 (m, 2H, POCH2), 5.00–4.66 (m, 2H, POCH2);
1
13C NMR (151 MHz, DMSO) δ 142.28, 142.19, 136.94, 136.90,
136.45, 136.41, 134.39, 131.31, 130.62, 130.57, 130.14, 128.98,
128.82, 128.64, 128.60, 128.54, 128.45, 128.18, 127.79, 127.62,
127.56, 127.48, 127.20, 126.67, 126.41, 125.27, 124.91, 124.37,
124.03, 123.30, 122.11, 118.48, 106.72, 68.44 (d, J = 6.8 Hz,
POCH2), 67.99 (d, J = 6.7 Hz, POCH2), 51.66 (d, J = 148.3 Hz,
CP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for C39H32NO3P:
594.2198, Found: 594.2207.
(243 MHz, DMSO) δ 10.82; H NMR (601 MHz, DMSO) δ
8.13 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 8.3 Hz, 1H), 7.95–7.90 (m,
1H), 7.88 (d, J = 8.2 Hz, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.61 (d,
J = 7.0 Hz, 1H), 7.55–7.48 (m, 1H), 7.43 (t, J = 7.6 Hz, 1H),
4.41 and 4.54 (AB system, J = 14.0 Hz, 2H, CH2), 4.38 (d, J =
18.8 Hz, 1H, CHP); HRMS (ESI-TOF) m/z: [MH]− Calcd. for
C18H17N2O5P: 371.0797; Found: 371.0790.
N-(Naphth--ylmethyl)naphth--ylaminomethylphosphonic
acid (4xd)
N-(Naphth-1-ylmethyl)naphth-1-ylaminomethylphosphonic
acid (4xd) was obtained as a white solid, m.p. 260–264°C. 31
P
Synthesis of N-substituted aminobenzylphosphonic
acids—general procedure
1
NMR (122 MHz, D2O) δ 16.12; H NMR (300 MHz, D2O) δ
8.15 (s, 1H), 7.96–7.83 (m, 2H), 7.79 (d, J = 8.3 Hz, 1H), 7.68
(d, J = 7.9 Hz, 1H), 7.63–7.41 (m, 5H), 7.30 (t, J = 7.4 Hz,
1H), 7.25–7.14 (m, 2H), 7.07 (d, J = 6.7 Hz, 1H), 4.68 (d, J =
18.5 Hz, 1H, CHP), 3.69 and 3.77 (AB system, J = 13.5 Hz, 2H,
CH2); HRMS (ESI-TOF) m/z: [MH]− Calcd. for C34H28NO3P:
530.1885, Found: 530.1863, while for monoester: C22H20NO3P:
376.1103, Found: 376.1112.
Triethyl phosphite (0.23 g, 1.85 mmole) was dissolved in
dichloromethane (20 mL) and trimethylsilyl bromide (2.55 g,
16.5 mmole) was added under an argon atmosphere. The
obtained solution was left for 24 h.
To the solution of Schiff base (1.7 mmole) in
dichloromethane (20 mL) cooled in ice-bath, a solution of
tri(trimethylsilyl) phosphite was added under argon. The solu-
tion was allowed to reach room temperature and was stirred at
room temperature for 20 h. Then the volatile components of the N-(Naphth--ylmethyl)naphth--ylaminomethylphosphonic
reaction mixture were evaporated and the oily residue was dis- acid (4xe)
solved in a methanolic solution of water (5%, 15 mL) and stirred N-(Naphth-1-ylmethyl)naphth-2-ylaminomethylphosphonic
at room temperature for an additional 24 h. The crude product acid (4xe) was obtained as a white solid, m.p. 199–200°C. 31P
was precipitated by the addition of diethyl ether (100 mL). After NMR (122 MHz, DMSO): δ 12.20; 1H NMR (601 MHz, DMSO)
washing with three portions of dry ether (10 mL each) products δ 8.03–7.86 (m, 5H), 7.81 (s, 2H), 7.75–7.59 (m, 2H), 7.58–7.45
of satisfactory purity crystallized from the solution.
(m, 3H), 7.44–7.30 (m, 2H), 4.43 (s, 2H, CH2), 4.28 (d, J =

PHOSPHORUS, SULFUR, AND SILICON
519
14.4 Hz, 1H, CHP); HRMS (ESI-TOF) m/z: [MH]− Calcd. for
132.28, 127.78, 126.55, 124.07, 124.02, 123.26, 122.64, 121.02,
120.94, 120.92, 118.57, 117.29, 105.13, 53.31 (d, J = 152.70,
CP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for C17H15N2O5P:
359.0797, Found: 357.0703.
C22H20NO3P: 376.1103, Found: 376.1094.
N-(Naphth--ylmethyl)anthracen--ylaminomethylphos-
phonic acid (4xf)
N-(Naphth--yl)amino-p-nitrobenzylphosphonic acid (4yc)
N-(Naphth-1-yl)amino-p-nitrobenzylphosphonic acid (4yc)
was obtained as a green solid, m.p. 123–126°C. 31P NMR
(243 MHz, MeOD) δ 15.30, 14.98; 1H NMR (601 MHz, MeOD)
δ 6.66–6.55 (m, 3H), 6.26–6.17 (m, 4H), 6.00–5.88 (m, 3H), 5.55
(s, 1H), 3.52 (d, J = 22.1 Hz, 1H, CHP); 13C NMR (151 MHz,
MeOD) δ 145.77, 144.31, 139.77, 132.83, 127.13, 127.10, 126.57,
123.97, 123.92, 123.14, 122.34, 121.39, 118.40, 55.37 (d, J
= 144.50, CP); HRMS (ESI-TOF) m/z: [MH]+ Calcd. for
C30H25N2O5P: C27H22N2O5P: 357.0640, Found: 357.0641.
N-(Naphth-1-ylmethyl)anthracen-9-ylaminomethylphospho-
nic acid (4xf) was obtained as a yellow solid, m.p. 189°C. 31P
NMR (243 MHz, DMSO) δ 12.20; 1H NMR (601 MHz, DMSO)
δ 8.82 (d, J = 8.9 Hz, 1H), 8.72 (s, 1H), 8.20–8.09 (m, 3H),
8.01–7.95 (m, 2H), 7.85 (d, J = 9.1 Hz, 1H), 7.71 (d, J = 7.1 Hz,
1H), 7.69–7.53 (m, 4H), 7.52–7.48 (m, 1H), 7.46 (t, J = 7.7 Hz,
1H), 7.44–7.39 (m, 1H), 5.99 (d, J = 22.0 Hz, 1H, CHP), 4.94
and 5.01 (AB system, J = 13.8 Hz, 2H, CH2); HRMS (ESI-TOF)
m/z: [MH]− Calcd. for C26H22NO3P: 426.1259, Found: 426.
1251.
N-(Napht--yl)anthracen--ylaminomethylphosphonic acid
(4yf) (MG/II/-pha)
N-(Naphth--ylmethyl)phenathren--ylaminomethylphos-
phonic acid (4xg)
N-(Napht-1-yl)anthracen-9-ylaminomethylphosphonic acid
(4yf) (MG/II/25-pha) was obtained as a yellow solid and decom-
posed at 267°C. 31P NMR (243 MHz, MeOD+NaOD/D2O) δ
20.61; 1H NMR (601 MHz, DMSO+NaOD/D2O) δ 8.48 (d, J =
13.2 Hz, 3H), 8.24 (d, J = 8.6 Hz, 1H), 7.51 (t, J = 7.8 Hz, 3H),
7.37 (d, J = 8.6 Hz, 3H), 7.27 (d, J = 7.8 Hz, 2H), 7.18 (t, J =
11.6 Hz, 1H), 7.13 (d, J = 7.5 Hz, 1H), 6.96 (d, J = 7.5 Hz, 1H),
6.73 (d, J = 8.4 Hz, 1H), 4.15 (d, J = 25.6 Hz, 1H, CHP); HRMS
(ESI-TOF) m/z: [MH]− Calcd. for C25H20NO3P: 412.1103,
Found: 412.1120.
N-(Naphth-1-ylmethyl)phenathren-9-ylaminomethylphosph-
onic acid (4xg) was obtained as a yellow solid, 229°C. 31P NMR
1
(243 MHz, DMSO) δ 11.81; H NMR (601 MHz, DMSO) δ
8.93 (d, J = 8.1 Hz, 1H), 8.88 (d, J = 8.3 Hz, 1H), 8.34 (s, 1H),
8.23 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.2 Hz, 1H), 8.02–7.96
(m, 2H), 7.87 (d, J = 7.8 Hz, 1H), 7.79–7.67 (m, 5H), 7.57 (t,
J = 7.3 Hz, 1H), 7.52 (dd, J = 15.1, 7.4 Hz, 2H), 5.65 (d, J =
16.4 Hz, 1H, CHP), 4.90 and 5.24 (AB system, J = 13.4 Hz, 2H,
CH2); 13C NMR (101 MHz, DMSO) δ 133.64, 132.09, 130.80,
130.69, 130.39, 130.25, 130.12, 128.99, 128.47, 128.16, 128.06,
127.67, 127.34, 127.26, 127.06, 126.53, 125.65, 124.86, 124.24,
123.85, 123.35, 55.00 (d, J = 140.4 Hz, CP), 48.30 (CH2); HRMS
(ESI-TOF) m/z: [MH]− Calcd. for C26H22NO3P: 426.1259,
Found: 426.1263.
Funding
This work was supported in part by Wroclaw Research Centre EIT+ under
the project BioMed (POIG.01.01.02–02–003/08) financed from the Euro-
pean Regional Development Fund (Operational Programme Innovative
Economy, 1.1.2) and in part by a statutory activity subsidy from the Pol-
ish Ministry of Science and Higher Education.
N-(Naphth--yl)amino-o-nitrobenzylphosphonic acid (4ya)
N-(Naphth-1-yl)amino-o-nitrobenzylphosphonic acid (4ya)
was obtained as a green-yellow solid, m.p. 130°C, decompo-
1
sition 131°C. 31P NMR (243 MHz, MeOD) δ 16.56; H NMR
References
(601 MHz, MeOD) δ 6.67 (d, J = 8.4 Hz, 1H), 6.49 (d, J =
8.2 Hz, 1H), 6.29–6.21 (m, 2H), 6.05–5.90 (m, 4H), 5.68 (d, J =
8.2 Hz, 1H), 5.66–5.60 (m, 1H), 5.02 (d, J = 7.5 Hz, 1H), 4.68 (d,
J = 22.0 Hz, 1H, CHP); 13C NMR (151 MHz, MeOD) δ 148.55,
139.59, 132.97, 131.35, 130.99, 126.63, 126.59, 126.50, 126.47,
124.32, 124.22, 124.00, 123.28, 122.19, 118.39, 116.56, 103.99,
50.02 (d, J = 147.30, CP); HRMS (ESI-TOF) m/z: [MH]+ Calcd.
for HRMS (ESI-TOF) m/z: [MH]+ Calcd for C17H15N2O5P:
359.0797, Found: 357.0744.
1. Sien´czyk, M.; Oleksyszyn, J. Curr. Med. Chem. 2009, 16, 1673-1687.
2. Mucha, A.; Kafarski, P.; Berlicki, Ł. J. Med. Chem. 2011, 54, 5955-5980.
3. Grzywa, R.; Sien´czyk, M. Curr. Pharm. Des. 2013, 19, 1154-1178.
4. Rakashandra, S.; Rana, F.; Rafiq, S.; Masood, A.; Amin, S. Biotechnol.
Molec. Biol. Rev. 2012, 7, 90-101.
5. Roy, D. M.; Walsh, L. A. Breast Cancer: Targets and Therapy 2014, 6,
81-91.
ˇ
6. Cufer, T. Radiol. Oncol. 2004, 38, 85-92.
7. Hamby, C. V.; Libre, M.; Uptat, S.; Wormser, G. P. Clin. Diagn. Lab.
Immunol. 2005, 12, 801-807.
8. Andersen, H.; Bier, F. F. Methods Mol. Biol. 2009, 509, 123-134.
9. Uttamchandani, M.; Yao, S. Q., Curr. Pharm. Des. 2008, 14, 2428-2438.
10. Carmona, S. J.; Sartor, P. A.; Leugizamón, M. S.; Campetella, O. E.;
Aguero, F. PLoS One. 2012, 7, e50748-50761.
N-(Naphth--yl)amino-m-nitrobenzylphosphonic acid (4yb)
N-(Naphth-1-yl)amino-m-nitrobenzylphosphonic acid (4yb)
was obtained as a green solid, m.p. 103–107°C. 31P NMR
(243 MHz, MeOD) δ 20.17; 1H NMR (601 MHz, MeOD) δ 6.91
(s, 1H), 6.64–6.53 (m, 2H), 6.38 (d, J = 7.7 Hz, 1H), 6.18 (d, J
= 8.2 Hz, 1H), 5.99 (t, J = 7.9 Hz, 1H), 5.93 (t, J = 7.7 Hz, 1H),
5.88 (t, J = 7.6 Hz, 1H), 5.65 (d, J = 8.2 Hz, 1H), 5.57 (t, J =
7.8 Hz, 1H), 4.95 (d, J = 7.6 Hz, 1H), 3.81 (d, J = 25.3 Hz, 1H,
CHP); 13C NMR (151 MHz, MeOD) δ 146.85, 139.44, 132.89,
11. Tyka, R. Tetrahedron Lett. 1970, 11, 677-680.
12. Kafarski, P.; Zon´, J. In: Aminophosphonic and Aminophosphinic Acids.
Chemistry and Biological Activity. Kukhar, V. P.; Hudson, H.R. Eds.;
John Wiley & Sons: Chichester 2000; Chapter 2: 33-59.
13. Tang, C.; Chen, Z.; Xiao, H.; Wang X.; Zhang G.; Hu, D. Phosphorus
Sulfur Silicon Relat. Elem. 2015, 190, 585-595.
14. Alcaine, A.; Marqués-Lópes, E.; Merino, P.; Tejero, T.; Herrer, R. P. Org.
Biomol. Chem. 2011, 9, 2777-2783.