Exceptional effect of nitro substituent on the phosphonation of imines: The first report on phosphonation of imines to α-iminophosphonates and α-(N-phosphorylamino)phosphonates

Article abstract of DOI:10.1039/c5ra14393d

A novel and chemoselective method is reported for the simple phosphonation of imines. By change of the electronic effects of the substituents, this method offers the selective synthesis of either α-iminophosphonates or α-(N-phosphorylamino)phosphonates. The mild reaction condition makes this protocol very attractive for synthesis of these two classes of phosphorous compounds.

Full text of DOI:10.1039/c5ra14393d

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Exceptional effect of nitro substituent on the
phosphonation of imines: the first report on
phosphonation of imines to a-iminophosphonates
and a-(N-phosphorylamino)phosphonates†
Cite this: RSC Adv., 2015, 5, 100070
*
*
Somayeh Motevalli, Nasser Iranpoor, Elham Etemadi-Davan
and Khashayar Rajabi Moghadam
Received 21st July 2015
Accepted 13th November 2015
A novel and chemoselective method is reported for the simple phosphonation of imines. By change of the
electronic effects of the substituents, this method offers the selective synthesis of either a-
iminophosphonates or a-(N-phosphorylamino)phosphonates. The mild reaction condition makes this
protocol very attractive for synthesis of these two classes of phosphorous compounds.
DOI: 10.1039/c5ra14393d
www.rsc.org/advances
phosphonates by C–H bond activation.11 The palladium-
catalyzed C-3 dehydrogenative phosphonation of coumarin
derivatives is a typical example for the regioselective sp2 C–H
Introduction
Organic phosphorus compounds, particularly phosphonates
and their derivatives are considered as an important class of
organophosphorus compounds with widespread applications
in medicinal1 and agricultural chemistry.2 In biological chem-
istry, phosphonate compounds play an important role as
pharmaceuticals due to their unique structure and charge
distribution.3 In addition, there are reports for their uses in
organic synthetic blocks4 and as phophorous-containing
ligands for metal-catalyzed C–C bond formation.5 Therefore,
development of more convenient and efficient methods to form
the C–P bond is a current topic and challengeable to researchers
in organic chemistry. The Michaelis–Arbuzov reaction is a well-
known and classical method for C–P bond formation discovered
by August Michaelis in 1898.6 During the last few years signi-
cant advances have been achieved in the development of cross-
coupling methodologies for the synthesis of different classes of
aromatic phosphonate compounds. For example, the rst cross-
coupling arylboronic acids and H-phosphonate diesters using
catalytic amounts of copper(II)oxide and phenanthroline cata-
lyst in order to yield aryl phosphonates have been reported by
Zhuang and co-workers.7 Recently, metal-catalyzed direct C–H
bond functionalization has offered one of the most effective and
efficient pathways for C–P bond construction.8–11 There are
some examples in the literature in the development of C–P bond
forming reactions via direct C–H bond cleavage. A pyridine-
directed C–H phosphonation reaction with H-phosphonates
by palladium catalyst is an example for the preparation of aryl
bond functionalization.10 Since a-aminophosphoric acids are
the most widely studied classes of biologically active
compounds12 as well as important surrogates for carboxylic
amino acids,13 chemists have been encouraged in the progress
of methods for their synthesis. The phosphonation of sp3 C–H
bonds of adjacent to tertiary amines is an operative oxidative
protocol to afford a-aminophosphonates.9,14,15 In this regard,
metal catalysts such as Cu,9,15a,b,c Fe,15d,e,f Ru,15g,h V,15i,j and Mo15k
in the presence of an oxidant have been applied. a-Imino-
phosphonates are direct precursors of a-aminophosphonates
through the conversion of the imine moiety into amine. In order
to serve this purpose, simple reduction of the C–N double bond
or addition of nucleophiles to the imine carbon has been
applied.16 Hence, direct approach to a-aminophosphonates
based on the rhodium-, palladium- and ruthenium-catalyzed
hydrogenation of the corresponding olenic precursors are
developing remarkably in recent years.12,17 Beletskaya and co-
workers have achieved success for the hydrogenation of a-imi-
nophosphonates to optically active a-aminophosphonates with
enantiomeric excesses up to 94% by [Rh(COD)2]+SbF6ꢀ/(R)-
BINAP complex.12 In continuation of our work on the Pd cata-
lyzed coupling reactions and phosphonation of aryl halides,18
we were interested in oxidative phosphorylation of C–H bond of
ortho position of benzylidene moiety of Schiff bases, mainly due
to the importance of oxidative cross-coupling reactions from the
atom- and step-economical points of view and environmentally
friendly synthetic approach.19 In addition, Schiff bases as an
important class of organic compounds possess a wide variety of
applications in many elds including analytical, biological, and
inorganic chemistry.20 However, to our surprise, the separated
products from this protocol showed that instead of C–H
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran.
E-mail: somayeh.motevalli@gmail.com; iranpoor@susc.ac.ir
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c5ra14393d
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Table 1 Effect of different reaction parameters on phosphonation of
activation, C]N bond of imine underwent phosphorylation,
and produced a-iminophosphonates and a-(N-phosphor-
ylamino)phosphonates. Since a-iminophosphonates are
precursors of a-aminophosphonic acids, their simple and easy
synthesis is of importance. According to the literature review,
various methods for the synthesis of a-iminophosphonates
have been reported.12,16,21 For example, a-iminophosphonates
were synthesized at 120–170 ꢁC via the Arbuzov reaction of
triethylphosphite with imidoyl chlorides prepared by reacting
thionyl chloride and amides.12 Addition of sodium salt of dia-
lkylphosphites to the triple bond of nitriles represents another
route to form such compounds as reaction intermediates to
produce phosphoryl aminophosphonates; however, in the
reactions of nitriles with H-phosphonate dialkyl esters, the
iminophosphonates were never isolated as the reaction inter-
mediates.21 Also, a-iminophosphonates were prepared by aza-
Wittig reaction of phosphazenes derived from the addition of
trimethylphosphine to azides with a-ketophosphonates.16 In
this article, we disclose a novel metal free reaction for direct
oxidative phosphonation of imines to a-iminophosphonates
(Scheme 1a) or oxidative phosphonation followed by addition
process to offer a-(N-phosphorylamino)phosphonates (Scheme
1b). To the best of our knowledge, direct a-phosphonation of
imines leading to a-iminophosphonates and also a-(N-phos-
phorylamino)phosphonates has not been reported before. In
this work, we report for the rst time on the effect of substitu-
ents on the aromatic ring for phosphonation of imines to offer
either a-iminophosphonates or a-(N-phosphorylamino)
phosphonates.
(4-nitro-benzylidene)-(4-methoxy-phenyl)-aminea
Entry
Base
Solvent
Tem. (ꢁC)
Yieldb (%)
1c
2
3
4
5
6
7
8
9
10
11
12d
13e
14f
15
16
17
DBU
DBU
DBU
DBU
DBU
DBU
DABCO
Et3N
K2CO3
LiNH2
NaOAc
DBU
DBU
DBU
DBU
DBU
CH3CN
CH3CN
PEG200
EtOH
80
80
80
80
80
80
80
80
80
80
80
80
80
80
60
35
RT
58
60
0
0
Toluene
Solvent free
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
77
22
0
0
0
0
25
80
10
15
75
Trace
0
DBU
a
Reaction conditions: (4-nitro-benzylidene)-(4-methoxy-phenyl)-amine
(1a) (1 mmol), H-phosphonate diethyl ester (4 mmol), base (4 mmol),
b
c
solvent (4 mL). Isolated yield. Pd(OAc)2 (10 mol%, 10 mg) as
a catalyst, AgOAc as an oxidant (1.5 equiv., 0.25 g) were added to the
d
reaction mixture. Triethylphosphite was added to the mixture in
e
place of H-phosphonate diethyl ester. The amount of H-phosphonate
f
diethyl ester is 2 mmol. The amount of used DBU is 2 mmol. All of
the reactions were monitored by TLC aer 24 h.
Results and discussion
Our initial study for Pd catalyzed C–H activation was on the
reaction of (4-nitro-benzylidene)-(4-methoxy-phenyl)-imine (1a),
with H-phosphonate diethylester in the presence of 4.0 equiv. of
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), Pd(OAc)2 (10 mol%),
and AgOAc (1.5 equiv.) as an oxidant in CH3CN at 80 ꢁC (Table 1,
entry 1). When the reaction was worked up, the obtained
product was found to be diethyl [a-(N-phosphoryl)-(4-methoxy-
phenyl)-amino]4-nitro-benzyl phosphonate (2a) in moderate
yield. We decided to eliminate both the Pd catalyst and the
oxidant from the reaction mixture. The obtained result showed
that again the product 2a is obtained in the same yield (Table 1,
entry 2). Further optimization of the reaction conditions was
focused on producing the product 2a in higher yield. Therefore,
the effects of different parameters were studied. The reaction
underwent with various solvent screenings and the best result
was acquired in toluene (Table 1, entry 5). According to the
results of Table 1, entry 6; the reaction did not work well under
solvent-free condition. In our optimization, several bases were
also studied for this reaction such as DABCO (1,4-diazabicyclo
[2.2.2]octane), Et3N, K2CO3, NaOAc, and LiNH2. The reaction
did not proceed by using DABCO, Et3N, K2CO3 and LiNH2 (Table
1, entries 7, 8, 9, 10) and using NaOAc as a base, the product was
obtained in low yield (Table 1, entry 11). According to these
results, we selected DBU as the most suitable base. Further-
more, by replacing the H-phosphonate diethyl ester with trie-
thylphosphite, the reaction failed under our optimized
conditions (Table 1, entry 12). Decreasing the amount of H-
phosphonate diethyl ester and DBU from four equimolar to two
resulted in very low yield (Table 1, entries 13, 14). Performing
the reaction at 60 ꢁC led to very good yield of the phosphonated
product 2a (Table 1, entry 15), while lowering the temperature to
ꢁ
35 C and room temperature, the reaction either was very slow
or did not occur at all (Table 1, entries 16, 17). One pot reaction
Scheme 1
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of 4-nitrobenzaldehyde, 4-methoxyaniline with H-phosphonate orientation effect on the yield and the scope of the reaction.
diethyl ester and DBU in toluene at 60 ꢁC gives a complex When the –NO2 group was placed in the ortho position of the
mixture.
ring, a very distinct steric effect was observed which changed
With optimized reaction conditions in hand; imine (1 the scope of the reaction. The characterization of the isolated
mmol), H-phosphonate diethyl ester (4 mmol), DBU (4 mmol), products showed that in these cases, instead of diphospho-
and toluene (4 mL) at 60 ꢁC, we examined various imines so as nates, the corresponding a-iminophosphonates have been ob-
to gauge the scope of the reaction (Table 2). Initially, various N- tained (Table 2, 2e, 2f, 2g). In this study, imines of (2-nitro-
aryl groups of (4-nitro-benzylidene)amines (1a–d) were investi- benzylidene)-(4-methoxy-phenyl)-amine (1e) and (2-nitro-
gated. When the substituent groups were placed on the para- benzylidene)-phenylamine (1g) produced their corresponding
position of the imino unit, we obtained higher yields of the a-iminophosphonates in 73% and 70%, respectively (Table 2,
diphosphonates, especially for those imines having electron- 2e, 2g). We also evaluated imines bearing electron withdrawing
withdrawing substituents (Table 2, 2a, 2b). (4-Nitro- groups other than –NO2 linked on the para-position of benzy-
benzylidene) amine bearing an electron-donating group at the lidene unit such as –Cl, and –F. First, the phosphonation
ortho-position such as –OCH3 has some steric effect and reaction of (4-chloro-benzylidene)-(4-methoxy-phenyl)-amine
therefore, slightly decreases the yield of the product (Table 2, (1l) was carried out under the same reaction conditions as
2c). The phosphonation reaction proceeded smoothly for 4- with 1a. Formation of a-aminophosphonate (Table 2, 2l24) from
nitrobenzylidene amine (1d) and the product was obtained in 1l directed us toward studying the electronic effect of the
71% yield (Table 2, 2d). We extended the phosphonation reac- substitutions. Since –NO2 as a strong withdrawing group has
tion to (2-nitro-benzylidene) amines in order to study the electronically impact on the phosphorylated products 2a–2g, we
did the phosphonation of (4-chloro-benzylidene)-(4-nitro-
phenyl)-amine (1m) with H-phosphonate diethyl ester and
ꢁ
DBU as a base in toluene at 60 C. The product was the corre-
sponding a-aminophosphonate (Table 2, 2m25). (4-Fluoro-
benzylidene)-(4-methoxy-phenyl)-amine (1n) as an imine pos-
sessing more electron-withdrawing halogen than 1l was also
applied in this cross-coupling reaction and the only obtained
product was found to be diethyl a-(4-methoxyphenylamino)-(4-
urorobenzyl)phosphonate in slightly higher yield than 2l
(Table 2, 2n). According to the observed results, the attachment
of –NO2 group on benzylidene unit of imine shows dis-
tinguishing electronic effect to product a-iminophosphonates
and a-(N-phosphorylamino)phosphonates (2a–2g). Encouraged
by these results, (3-nitro-benzylidene)-(4-methoxy-phenyl)-
amine (1k) was chosen as another example to study the orien-
tation and electronic effects of phosphonation reaction. It was
converted into the corresponding a-aminophosphonate with
excellent yield (Table 2, 2k23). As a result, the reaction is appli-
cable to substrates bearing –NO2 group in ortho and para
position of imines in order to generate a-iminophosphonate
and a-(N-phosphorylamino)phosphonates, and because of
subtle steric and electronic effects, it is highly chemoselective.
Although the mechanism for this reaction is unclear, we
proposed the following probable mechanism. In the rst step,
diethyl phosphonate anion and salt A is formed from the
reaction of H-phosphonate diethyl ester and DBU as a base.
Then, the attack of diethyl phosphonate anion to imine in
Table 2 Phosphonation of imines in toluene using HP(O)(OEt)2 and
DBUa
ꢁ
toluene at 60 C produces adduct I which may be a key inter-
mediate in the reaction. The next step includes oxidation of
adduct I by salt A as shown in Scheme 2 and a-iminophosph-
onate forms in this stage. In the case of para-nitro derivatives,
subsequently, the obtained a-iminophosphonate reacts with
another equimolar of H-phosphonate diethyl ester to produce a-
(N-phosphorylamino)phosphonates. DBU is
a
chemical
compound used in organic synthesis as a catalyst, a complexing
ligand, and a well-known non-nucleophilic base. Herein, we
introduce dual possible role of DBU both as base and as
oxidant. To prove the possible role of DBU as an oxidant in the
a
All of the reactions have been monitored by TLC aer 24 h.
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Scheme 3
Experimental section
Melting points were determined and recorded in open capil-
laries with Buchi B-545 melting point instrument and were not
corrected. 1H and 13C NMR spectra were recorded on a Brucker
Avance DPX-250 spectrometers using CDCl3 and tetramethylsi-
lane (TMS) as internal standard in pure deuterated solvents. 31
P
Scheme 2 Proposed mechanism.
NMR spectra were recorded on a Brucker Avance DPX-400 Ultra
shield. FTIR spectra were run on a Shimadzu FTIR-8300 spec-
trophotometer. Mass spectra were acquired on a Shimadzu
GCMS-QP 1000 EX instrument at 70 eV. CHN analyses were
performed with a Vario EL, ElementarAnalyser system GmbH
(Hanau). The reaction monitoring was carried out on silica gel
analytical sheets. Purication of products was carried out by
column chromatography on the column of silica gel 60 Merck
(230–240 mesh) in glass columns (2 or 3 cm diameter).
reaction, we carried out four control experiments. According to
the results of these transformations, we conducted the rst
control experiment involving phosphonation of (4-nitro-
benzylidene)-(4-methoxy-phenyl)-amine 1a in the absence of
DBU in EtOH as a solvent at 60 ꢁC. The reaction monitoring
showed that 1a was converted almost completely into the cor-
responding a-aminophosphonate within 24 h. Then, DBU was
added to the reaction mixture and the desired product 2a was
produced. In the second control experiment, the reaction 1a
with H-phosphonate diethyl ester proceeded in toluene and in
the absence of DBU at 60 ꢁC. TLC analysis represented that the
reaction did not occur. We expanded the control experiments
using 1e as a starting material in both EtOH and toluene in the
absence of DBU at 60 ꢁC. The corresponding a-amino-
phosphonate was obtained in EtOH and then the addition of
DBU produced a-iminophosphonate 2e. However, the reaction
failed in toluene in the absence of DBU. Therefore, the presence
of DBU plays a synergic role to produce the desired products. In
order to get more insight into the proposed mechanism, the
reaction of 1g with H-phosphonate diethyl ester and DBU in
toluene at 60 ꢁC was done. The analysis of the reaction mixture
supports the hypothesis that DBU acts as an oxidant through
recognizing the reduced form of DBU in the reaction mixture.
General procedure for the preparation of imines22
Aldehyde (5.0 mmol) and 5.0 mmol of amine in ethanol (10.0
mL) were placed in a ask equipped with a magnetic stirrer, and
reux condenser. The reaction mixture was reuxed with stir-
ring for 24 h. Aer completion, the reaction mixture was cooled
to room temperature, and then mixture was le for crystalliza-
tion. Aer recrystallization from ethanol, the pure products
were obtained with excellent yield (1a–n).
General procedure for phosphorylation of imines
A mixture of imine (1.0 mmol), H-phosphonate diethyl ester (0.5
mL, 4.0 mmol), and DBU (0.48 mL, 4.0 mmol), in toluene (4 mL)
was heated at 60 ꢁC for 24 h. Aer completion, the reaction
mixture was cooled to room temperature and the solvent was
evaporated under vacuum. Then, the crude organic mixture was
puried by silica gel column chromatography (petroleum ether/
ethyl acetate 4 : 1) to obtain the desired products in moderate to
excellent yield.
1
According to the H- and 13C-NMR (see the ESI†), the presence
of N–H and C–H signals at 4.9 and 3.18 ppm, respectively and
the absence of the signal for the carbon of C]N and the pres-
ence of C–H signal at 77.2 ppm in the reduced form of DBU are
strong evidences for the reduction of DBU in this processes.
Additionally, to prove the second phosphorylation in the
proposed manner, we prepared the a-iminophosphonate of
imine 1a by described procedure in the literature.12 Then, the
puried a-iminophosphonate was allowed to react with H-
phosphonate diethyl ester and DBU in toluene at 60 ꢁC. Aer 24
h, bisphosphonate 2a was obtained as the main product
(Scheme 3).
Typical procedure for the preparation of N-(4-methoxyphenyl)-
4-nitrobenzamide26
To a reuxing solution of Ph2PCl (0.27 mL, 1.5 mmol) and
imidazole (0.30 g, 4.5 mmol) in 5 mL dichloromethane, iodine
(0.37 g, 1.5 mmol) and 4-nitrobenzoic acid (0.33 g, 2.0 mmol)
were added consecutively. Aer few minutes, p-anisidine (0.24
g, 2.0 mmol) was added to the reaction mixture and was le
stirring at reux for 20 min. Then, the organic layer was washed
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with saturated aqueous sodium carbonate (3 ꢂ 5 mL) and NMR (CDCl3, 250 MHz) d (ppm): 8.16 (d, 2H, J ¼ 9 Hz), 8.08 (d,
aqueous sodium thiosulfate (2 ꢂ 5 mL), and dried over Na2SO4. 2H, J ¼ 9 Hz), 7.63 (d, 2H, J ¼ 9 Hz), 7.21 (d, 2H, J ¼ 9 Hz), 5.83
2
3
The desired product was obtained by column chromatography (dd, 1H, J (H–P) ¼ 24.6 Hz, J (H–P) ¼ 11.8 Hz), 4.31–3.85 (m,
over silica gel with n-hexane/ethyl acetate (5 : 1) as eluent (yield: 8H), 1.35 (t, 3H, J ¼ 7 Hz), 1.29 (mt, 3H), 1.20 (t, 3H), 1.12 (t, 3H,
88%).
J ¼ 7 Hz); 13C-NMR (CDCl3, 62.9 MHz) d (ppm): 147.8, 146.2,
3
2
144.5, 141.5 (d, J (C–P) ¼ 3.5 Hz), 131.1 (d, J (C–P) ¼ 7.9 Hz),
130.4, 123.6 (d, 2J (C–P) ¼ 7.9 Hz), 63.0–63.7 (m, 4C, –CH2–), 58.4
(dd, –CH–, 2J (C–P) ¼ 5.5 Hz, 1J (C–P) ¼ 161.0 Hz), 15.9–16.4 (m,
4C, –CH3); 31P-NMR (CDCl3, 162 MHz) d (ppm): 19.28 (d, 3J (P–P)
¼ 20.5 Hz), 4.51 (d, 3J (P–P) ¼ 20.5 Hz); IR (KBr): n [cmꢀ1] 2977.9,
2916.2, 1595.9, 1519.8, 1350.1, 1249.8, 1026.1, 972.1; MS (70 eV,
EI): m/z (%): 545, M+ (0.4), 408 (100.0); anal. calcd for
Typical procedure for the preparation of N-(p-anisyl)-4-
nitrobenzenecarboxyimidoyl chloride12
A mixture of N-(4-methoxyphenyl)-4-nitrobenzamide (0.27 g, 1.0
mmol) and thionylchloride (0.38 mL, 5.3 mmol) were stirred at
ꢁ
80 C for 8 h. Excess SOCl2 was removed under reduced pres-
sure, and the residue was puried by column chromatography
over silica gel using n-hexane/ethyl acetate as eluent (7 : 1)
affording the product as pale yellow crystals; yield: 0.24 g (75%).
C
21H29N3O10P2: C, 46.24; H, 5.36; N, 7.70. Found: C, 46.25; H,
5.75; N, 8.00.
Diethyl-[a-(N-phosphoryl)-(2-methoxy-phenyl)-amino]4-nitro-
ꢁ
benzyl phosphonate (2c). Pale yellow solid (mp: 115–115.5 C);
Typical procedure for the preparation of diethyl a-(p-
anisylimino)-4-nitrobenzylphosphonate12
1H-NMR (CDCl3, 250 MHz) d (ppm): 8.12–8.09 (m, 2H), 7.91–7.88
(m, 2H), 6.76–6.60 (m, 2H), 6.49–6.41 (m, 1H), 6.10 (d, 1H, J ¼ 7.5
Hz), 5.68–5.64 (m, 1H), 4.21–3.96 (m, 11H), 1.23–1.09 (m, 12H);
13C-NMR (CDCl3, 62.9 MHz) d (ppm): 13C-NMR (CDCl3, 62.9
To a 3-necked round ask equipped with a magnetic stirrer, N-
(p-anisyl)-4-nitrobenzenecarboxyimidoyl chloride (0.32 g, 1.0
mmol) and triethylphosphite (0.25 mL, 1.5 mmol) was added
under Ar. The reaction mixture was stirred at 140 ꢁC for 8 h and
then puried by column chromatography over silica gel with n-
hexane/ethyl acetate as eluent (4 : 1) giving iminophosphonate
as a yellow oil; yield: 0.3 g (70%).
2
MHz) d (ppm): 158.2, 143.2, 136.3, 130.2 (d, J (C–P) ¼ 4.1 Hz),
129.6, 122.5, 119.6, 118.6, 116.6, 64.1–64.4 (m, 4C, –CH2–), 57.8
(broad s, 1C, –CH–), 55.7 (1C, –OCH3), 16.2 (broad s, 4C, –CH3);
31P-NMR (CDCl3, 162 MHz) d (ppm): 20.76, 17.51; IR (KBr): n
[cmꢀ1] 2985.6, 2931.6, 1596.9, 1519.8, 1458.1, 1342.4, 1249.8,
1164.9, 1118.6, 1026.1, 972.1, 856.3, 740.6; MS (70 eV, EI): m/z
(%): 530, M+ (5.7), 255 (100.0); anal. calcd for C22H33N2O9P2: C,
49.81; H, 6.08; N, 5.28. Found: C, 49.50; H, 5.78; N, 5.08.
Diethyl-[a-(N-phosphoryl)-(phenyl)-amino]4-nitro-benzyl phos-
Typical procedure for the preparation of diethyl [a-(N-
phosphoryl)-(4-methoxy-phenyl)-amino]4-nitro-benzyl
phosphonate (2a)
To a 25 mL round ask containing a-iminophosphonate (0.21 g, phonate (2d). Yellow oil; 1H-NMR (CDCl3, 250 MHz) d (ppm): 8.06
0.5 mmol) prepared from previous reaction was added H- (d, 2H, J ¼ 8.2 Hz), 7.51 (d, 2H, J ¼ 8.7 Hz), 7.20–7.14 (m, 3H),
phosphonate diethyl ester (0.125 mL, 1.0 mmol), and DBU 6.95–6.90 (m, 2H), 5.66 (dd, 1H, 2J (H–P) ¼ 23.5 Hz, 3J (H–P) ¼ 11.5
(0.145 mL, 1.0 mmol), in toluene (2 mL) and heated at 60 ꢁC for Hz), 4.25–3.74 (m, 8H), 1.28 (t, 3H, J ¼ 7 Hz), 1.21 (mt, 3H), 1.09
24 h. The solvent was removed in vacuo. Then, the crude organic (mt, 3H), 1.02 (t, 3H, J ¼ 7 Hz); 13C-NMR (CDCl3, 62.9 MHz)
mixture was puried by silica gel column chromatography d (ppm): 147.9, 131.8 (d, 2J (C–P) ¼ 8.4 Hz, two peaks), 131.6, 128.3,
(petroleum ether/ethyl acetate 4 : 1) to obtain the bisphospho- 128.0, 123.2, 123.0, 62.6–63.1 (m, 4C, –CH2–), 59.6–59.7 (m, 1C,
nate product.
–CH–), 54.3 (broad s, 1C, –CH–), 15.9–16.4 (m, 4C, –CH3); 31P-NMR
Diethyl
[a-(N-phosphoryl)-(4-methoxy-phenyl)-amino]4- (CDCl3, 162 MHz) d (ppm): 19.60, 3.08; IR (KBr): n [cmꢀ1] 2985.6,
nitro-benzyl phosphonate (2a). Diethyl [a-(N-phosphoryl)-(4- 2931.6, 1596.9, 1527.5, 1490.1, 1442.7, 1350.1, 1257.5, 1164.9,
methoxy-phenyl)-amino]4-nitro-benzyl phosphonate (2a) was 1026.1, 972.1, 864.1, 794.6; MS (70 eV, EI): m/z (%): 500, M+ (1.0),
obtained as yellow oil; yield: 0.414 g, 78%; 1H-NMR (CDCl3, 250 363 (100.0); anal. calcd for C21H31N2O8P2: C, 50.40; H, 6.04; N,
MHz) d (ppm): 8.06 (d, 2H, J ¼ 9 Hz), 7.49 (d, 2H, J ¼ 9 Hz), 6.82 5.60. Found: C, 50.12; H, 5.72; N, 5.30.
(d, 2H, J ¼ 9 Hz), 6.66 (d, 2H, J ¼ 9 Hz), 5.63 (dd, 1H, 2J (H–P) ¼
Diethyl a-(p-anisylimino)-2-nitrobenzylphosphonate (2e).
23.1 Hz, 3J (H–P) ¼ 11 Hz), 4.23–3.78 (m, 8H), 3.70 (d, 3H, J ¼ 1 Pale yellow solid (mp: 77–78 ꢁC); 1H-NMR (CDCl3, 250 MHz)
Hz), 1.30 (t, 3H, J ¼ 7 Hz), 1.20 (mt, 3H), 1.10 (mt, 3H), 1.02 (t, d (ppm): 8.09–8.07 (m, 1H), 7.75–7.73 (m, 1H), 7.43–7.24 (m,
3H, J ¼ 7 Hz); 13C-NMR (CDCl3, 62.9 MHz) d (ppm): 13C-NMR 4H), 7.07–7.03 (m, 2H), 4.01–3.87 (m, 7H), 1.21–1.18 (m, 6H);
(CDCl3, 62.9 MHz) d (ppm): 159.0, 147.7, 142.1 (d, 2J (C–P) ¼ 13C-NMR (CDCl3, 62.9 MHz) d (ppm): 161.4, 159.3, 149.7, 132.5,
2
4
6.0 Hz), 132.9, 131.9 (d, J (C–P) ¼ 8.4 Hz), 129.4, 123.2, 113.4, 130.0, 126.8 (d, J (C–P) ¼ 4.0 Hz), 122.8, 121.2, 120.0, 114.2,
2
1
2
62.6–63.0 (m, 4C, –CH2–), 58.5 (dd, –CH–, J (C–P) ¼ 8.3 Hz, J 113.6, 62.7 (d, 2CH2, J (C–P) ¼ 5.3 Hz), 55.6 (OCH3), 16.0 (d,
3
(C–P) ¼ 162.1 Hz), 55.2 (1C, –OCH3), 15.9–16.4 (m, 4C, –CH3); 2CH3, J (C–P) ¼ 6.4 Hz); 31P-NMR (CDCl3, 162 MHz) d (ppm):
3
31P-NMR (CDCl3, 162 MHz) d (ppm): 19.94 (d, J (P–P) ¼ 21.8 2.76; IR (KBr): n [cmꢀ1] 2985.6, 2931.6, 2839.0, 1643.2, 1604.7,
Hz), 5.71 (d, 3J (P–P) ¼ 21.8 Hz); IR (KBr): n [cmꢀ1] 2985.6, 1512.1, 1450.4, 1388.7, 1296.1, 1249.8, 1172.6, 1026.1, 972.1,
2931.6, 2869.9, 1604.7, 1519.8, 1350.1, 1249.8, 1026.1, 964.3, 833.2, 756.0; anal. calcd for C18H21N2O6P: C, 55.10; H, 5.39; N,
864.1; anal. calcd for C22H32N2O9P2: C, 49.81; H, 6.08; N, 5.28. 7.14. Found: C, 54.85; H, 5.04; N, 6.84.
Found: C, 49.42; H, 5.83; N, 4.98.
Diethyl-[a-(N-phosphoryl)-(4-nitro-phenyl)-amino]-4-nitro-
benzyl phosphonate (2b). Pale yellow solid (mp: 87–88 C); H- MHz) d (ppm): 8.13–8.08 (m, 1H), 7.79–7.75 (m, 1H), 7.62–7.54
Diethyl
a-(ortho-anisylimino)-2-nitrobenzylphosphonate
1
(2f). Pale yellow solid (mp: 147–148 ꢁC); H-NMR (CDCl3, 250
1
ꢁ
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(m, 1H), 7.40–7.25 (m, 4H), 7.12–7.11 (m, 1H), 7.10–7.08 (m,
1H), 4.08–3.81 (m, 4H), 3.78 (d, 3H, J ¼ 1.8 Hz), 1.22 (mt, 3H),
1.13 (mt, 3H); 13C-NMR (CDCl3, 62.9 MHz) d (ppm): 157.6, 156.2,
147.9, 133.0, 132.3, 130.6, 128.6, 126.6, 126.4, 121.3, 120.4,
113.8, 111.9, 62.6 (d, 2CH2, 2J (C–P) ¼ 4.8 Hz), 55.8 (OCH3), 15.9–
16.1 (m, 2CH3); 31P-NMR (CDCl3, 162 MHz) d (ppm): 2.50; IR
(KBr): n [cmꢀ1] 2977.9, 2893.0, 1604.7, 1504.4, 1473.3, 1300.1,
1280.6, 1249.8, 1164.9, 1010.6, 979.8, 840.9, 763.8; MS (70 eV,
EI): m/z (%): 392, M+ (1.1), 223 (100.0); anal. calcd for
C18H21N2O6P: C, 55.10; H, 5.39; N, 7.14. Found: C, 55.38; H,
5.74; N, 7.46.
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Diethyl a-(phenylimino)-2-nitrobenzylphosphonate (2g).
1
Yellow oil, H-NMR (CDCl3, 250 MHz) d (ppm): 8.12–8.09 (m,
1H), 7.78–7.74 (m, 1H), 7.60–7.50 (m, 5H), 7.33–7.30 (m, 2H),
4.03–3.91 (m, 4H), 1.16 (t, 6H, J ¼ 7 Hz); 13C-NMR (CDCl3, 62.9
MHz) d (ppm): 157.9, 156.8, 151.8, 141.3, 132.9, 131.0, 129.0,
128.7, 126.9 (d, 3J (C–P) ¼ 6.3 Hz), 121.3, 113.7, 62.8 (d, 2CH2, 2J
(C–P) ¼ 5.6 Hz), 16.0 (d, 2CH3, 3J (C–P) ¼ 6.7 Hz); 31P-NMR
(CDCl3, 162 MHz) d (ppm): 4.49; IR (KBr): n [cmꢀ1] 2985.6,
2931.6, 1658.7, 1596.9, 1504.4, 1473.5, 1388.7, 1257.5, 1164.9,
1110.9, 1049.2, 1010.6, 979.8, 840.9, 748.3; MS (70 eV, EI): m/z
(%): 362, M+ (0.4), 179 (100.0); anal. calcd for C17H19N2O5P: C,
56.35; H, 5.29; N, 7.73. Found: C, 56.05; H, 5.01; N, 7.50.
Diethyl a-(p-anisylimino)-4-nitrobenzylphosphonate. Yellow
oil; 1H-NMR (CDCl3, 250 MHz) d (ppm): 8.17 (d, 2H, J ¼ 16.7 Hz),
7.77 (d, 2H, J ¼ 16.7 Hz), 7.19–6.90 (m, 4H), 4.73–4.23 (m, 4H),
3.91 (s, 3H), 1.39–1.14 (m, 6H); 13C-NMR (CDCl3, 62.9 MHz)
d (ppm): 198.7, 160.5, 151.5, 145.0, 137.5 (d, 2J (C–P) ¼ 4.9 Hz),
129.3 (d, 2J (C–P) ¼ 4.5 Hz), 122.7, 122.6, 115.5, 60.2 (d, –CH2–,2J
(C–P) ¼ 5.7 Hz), 53.0 (1C, –OCH3), 16.6 (d, –CH3, 3J (C–P) ¼ 4.7
Hz); 31P-NMR (CDCl3, 162 MHz) d (ppm): 4.85.
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Conclusions
In summary, we have developed a novel and efficient method of
oxidative phosphonation of imines with H-phosphonate diethyl
ester using DBU both as base and as oxidant with high che-
moselectivity. Also, we studied the electronic and orientation
effects of substituents on the phosphonation of imines.
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Acknowledgements
We acknowledge the support of this work by Shiraz university
research council and the grant from National Elite Foundation
of Iran.
Notes and references
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