Preparation of dialkyl 1-(Alkylamino)alkylphosphonates, alkyl [1-(Alkylamino)alkyl]phenylphosphinates and [1-(Alkylamino)alkyl] diphenylphosphine oxides via in situ generated iminium ions

Article abstract of DOI:10.1055/s-0029-1218817

The reaction of trialkyl phosphites, dialkyl phenylphosphonites or alkyl diphenylphosphinites with N-alkylalkanimines in the presence of hydrogen chloride gives dialkyl 1-(alkylamino)alkylphosphonates, alkyl amino)alkyl]phenylphosphinates or [1-(alkylamino)alkyl]diphenylphosphine oxides respectively, via Arbusov-like reaction of iminium salts generated in situ from N-alkylalkanimines. This reaction is an alternative and competitive to known method of preparation based on the addition of H-P compounds to N-alkylalkanimines, because it gives higher yields, no heating is necessary, and the isolation of products is easy. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0029-1218817

PAPER
2437
Preparation of Dialkyl 1-(Alkylamino)alkylphosphonates, Alkyl
[1-(Alkylamino)alkyl]phenylphosphinates and [1-(Alkylamino)alkyl]di-
phenylphosphine Oxides via ‘In Situ’ Generated Iminium Ions
1
-(Alkylamino)alkyl-S
u
a
bstituted
P
h
l
osphor
d
us
D
erivativ
e
es via Imin
m
ium Ions ar Goldeman, Mirosław Soroka*
Politechnika Wrocławska, Department of Chemistry, Wybrzeże Wyspiańskiego 27, 50370 Wrocław, Poland
Fax +48(71)3284064; E-mail: miroslaw.soroka@pwr.wroc.pl
Received 27 January 2010; revised 7 April 2010
Indeed, when we examined the reaction of triethyl phos-
phite with N-(triphenylmethyl)methanimine in the pres-
ence of stoichiometric amounts of hydrogen chloride in a
dry aprotic solvent (Et2O or CH2Cl2) at temperatures be-
Abstract: The reaction of trialkyl phosphites, dialkyl phenylphos-
phonites or alkyl diphenylphosphinites with N-alkylalkanimines in
the presence of hydrogen chloride gives dialkyl 1-(alkylami-
no)alkylphosphonates, alkyl [1-(alkylamino)alkyl]phenylphosphi-
nates
or
[1-(alkylamino)alkyl]diphenylphosphine
oxides low –10 °C [to prevent dealkylation of P(OEt)3], we found
that, using 31P NMR spectroscopy, that the crude reaction
mixture contains 95% of diethyl [(triphenylmethyl)ami-
no]methylphosphonate and a minor amount of diethyl
phosphonate, unreacted triethyl phosphite and about 2%
of an unidentified compound (d = 29.8). A similar result
was obtained when N-(triphenylmethyl)ethanimine was
employed. To exclude the possibility that the triethyl
phosphite was dealkylated by the hydrogen chloride to di-
ethyl phosphonate, which could also give the final diethyl
1-[(triphenylmethyl)amino]ethylphosphonate (1b) in the
reaction with N-(triphenylmethyl)ethanimine, we per-
formed a cross-experiment. Thus, when we mixed stoichi-
ometric amounts of N-(triphenylmethyl)ethanimine,
triethyl phosphite, dimethyl phosphonate, and hydrogen
chloride in dichloromethane, at a temperature below –10
respectively, via Arbusov-like reaction of iminium salts generated
‘in situ’ from N-alkylalkanimines. This reaction is an alternative
and competitive to known method of preparation based on the addi-
tion of H–P compounds to N-alkylalkanimines, because it gives
higher yields, no heating is necessary, and the isolation of products
is easy.
Key words: aminophosphonates, aminophosphinates, imines,
Schiff bases, nucleophilic addition
In 2006 we described1 in this journal the preparation of di-
alkyl 1-hydroxyalkylphosphonates in the reaction of tri-
alkyl phosphites with oxonium salts prepared ‘in situ’
from aldehydes or ketones and hydrogen chloride. Con-
tinuing our studies on the reaction of trialkyl phosphites
with onium salts, we turned our attention to iminium salts.
Alkanimines are much stronger bases than aldehydes or
ketones, therefore they should be more easily converted
into the corresponding iminium salts by hydrogen chlo-
ride. Then, the iminium salt, a very strong electrophile
(and less sterically hindered than the starting
alkanimine2), should react with nucleophilic trialkyl phos-
phite giving the intermediate phosphonium salt, which
should be spontaneously transformed to give the final di-
alkyl 1-(alkylamino)alkylphosphonate, analogously to the
last step in the Arbuzov reaction (Scheme 1).
1
°C, we observed (31P and H NMR) only diethyl 1-[(tri-
phenylmethyl)amino]ethylphosphonate (1b, ~94%), but
not dimethyl 1-[(triphenylmethyl)amino]ethylphospho-
nate (Scheme 2). We identified also unreacted dimethyl
phosphonate (d = 11.7), methyl phosphonate (d = 8.4),
and traces of diethyl phosphonate (d = 10.0).
O
P
OEt
:P OEt
OEt
OMe
OMe
H-Cl
H
+
+
CPh3
N
CH2Cl2
OEt
O
P
OEt
O
R1
R1
H
N+
OMe
Cl–
(AlkO)3P
+
H-Cl
H
P
+ Et-Cl
N
N
CPh3
OMe
R2
R2
H
Scheme 2
Cl–
P+ OAlk
R1
N
OAlk
R1
O
OAlk
P
R2
– Alk-Cl
R2
N
OAlk
After NMR measurements, the crystalline diethyl 1-
[(triphenylmethyl)amino]ethylphosphonate (1b) was iso-
lated from the reaction mixture in 82% yield, and its struc-
ture was confirmed. This double cross-experiment shows
additionally that hydrogen chloride neither activates di-
alkyl phosphonate nor dealkylates the trialkyl phosphite
under the applied reaction conditions.
OAlk
H
H
Scheme 1
SYNTHESIS 2010, No. 14, pp 2437–2445
Advanced online publication: 15.06.2010
x
x.
x
x
.
2
0
1
0
To test this reaction, we examined some representative N-
(triphenylmethyl)alkanimines under similar conditions. In
DOI: 10.1055/s-0029-1218817; Art ID: T02310SS
© Georg Thieme Verlag Stuttgart · New York

2438
W. Goldeman, M. Soroka
PAPER
all cases the yields assayed by 31P NMR were between bound, to the alkanimines (Schiff bases) was used most
85% and 98%. In the cases of N-(triphenylmethyl)alkan- frequently. This reaction was described for the first time
imines derived from aromatic aldehydes, we obtained in 1952 by Pudovik,6a–c who used ‘anils’ (imines from
several crystalline dialkyl 1-[(triphenylmethyl)amino]alk- aniline) and dialkyl phosphonates in the presence of a cat-
ylphosphonates 1g–k with excellent yields, just by simple alytic amount of a base, and independently by Fields,6d
evaporation of the solvent. It is worthy of note that these who described the addition of dialkyl phosphonates to N-
compounds were not previously available.3 Also good re- alkyl-substituted alkanimines. Very soon this reaction
sults were obtained when some other N-alkylalkanimines was adapted by others, and became one of the best meth-
were applied.
ods for the preparation of N-substituted 1-aminoalkyl-
phosphonates, 1-aminoalkylphosphinates,14 and 1-
aminoalkylphosphine oxides.15 In fact, the papers pub-
lished later are modifications of the method published by
Pudovik and Fields. As ammonia does not give Schiff
bases, it was necessary for the preparation of the N-unsub-
stituted 1-aminoalkylphosphonates to use ‘ammonia
equivalents’, for example: benzylamine,16 optically active
1-phenylethylamines,17 1-phenylcycloalkylamine,18 benz-
hydrylamine,19 tritylamine,3 other amines,20 and also hy-
drazine.21
Also bis(2-chloroethyl) phenylphosphonite reacts with N-
(triphenylmethyl)methanimine in the presence of hydro-
gen chloride giving 2-chloroethyl phenyl{[(triphenyl-
methyl)amino]methyl}phosphinate (2a) in 79% yield.
Similarly, ethyl diphenylphosphinite reacts with N-(tri-
phenylmethyl)methanimine to give diphenyl{[(triphenyl-
methyl)amino]methyl}phosphine oxide (3c) in 79% yield.
All products were sufficiently pure for direct application,
however, if the product did not crystallize after evapora-
tion of the solvent, it could be isolated as the correspond-
ing oxalate, as described by Kowalik et al.4 The results are
summarized in Table 1.
Usually, the reaction between alkanimine (Schiff base)
and dialkyl phosphonate starts spontaneously22 because
the Schiff base is basic enough to remove a proton from
the H–P moiety in the dialkyl phosphonate, simultaneous-
ly activating itself to the corresponding iminium ion.
However, the reaction is usually slow because the low ba-
sicity of alkanimines. To speed up the reaction it is neces-
sary to increase the temperature above 100 °C. An
addition of dialkyl phosphonates to alkanimines has also
some other limitations. The first is the low reactivity of
sterically hindered Schiff bases, for example, as dis-
cussed,3 the imines derived from triphenylmethylamine
and aromatic aldehydes, do not react with diethyl phos-
phonate. The second limitation is a side reaction, in many
cases dialkyl phosphonates react with alkanimines not by
addition, but by redox reaction, to give a secondary amine,
the product of the formal reduction of the Schiff base. The
main problem is the very low nucleophilicity of dialkyl
phosphonates.7 Our protocol solves all of these limita-
tions.
Surprisingly, we found no exact precedent for a similar re-
action,5 although the syntheses of dialkyl 1-(alkylami-
no)alkylphosphonates have been extensively studied and
described in the literature.6 We only found a few notes
concerning the reactions of trialkyl phosphites with alk-
animines, despite the fact that trialkyl phosphites are
obviously much better nucleophiles than dialkyl phospho-
nates.7 Trialkyl phosphites are P-nucleophiles since a free
electron pair is localized on the phosphorus atom. In 1969
Pudovik and Pudovik8 described trialkyl phosphites as un-
reactive towards benzylideneamines. Only in the presence
of phenol did trialkyl phosphites reacted with benzyli-
deneamines at temperatures above 130 °C giving the
corresponding dialkyl (alkylamino)phenylmethylphos-
phonates, but in rather low yields (23–30%). Despite this,
many authors have described the preparation of 1-ami-
noalkylphosphonates in a so-called ‘three component
coupling’ reaction9 (trialkyl phosphite, amine, and alde-
hyde), according to our experimental data, the real re-
agents in this reaction are in fact dialkyl phosphonates
obtained ‘in situ’ by instant hydrolysis of the starting tri-
alkyl phosphites by water produced when amine reacts
with the aldehyde. To the best of our knowledge, the only
precedent for the successful application of trialkyl phos-
phite to the preparation of a new P–C–N moiety is by anal-
ogy to the aminoalkylation, amidoalkylation reaction,
described by Shono et al.,10 and later by others.11,12
In summary, we have found that the reaction of trialkyl
phosphites, dialkyl phenylphosphonites as well as alkyl
diphenylphosphinites, with N-alkylalkanimines in the
presence of hydrogen chloride at a temperature below –10
°C is an excellent method for the preparation of dialkyl 1-
(alkylamino)alkylphosphonates, alkyl [1-(alkylami-
no)alkyl]phenylphosphinates,
and
[1-(alkylami-
no)alkyl]diphenylphosphine oxides. This procedure is
very simple, no heating is necessary, and gives the final
products with good yields. Moreover, the products are
usually of sufficient purity for direct use without the ne-
cessity for any additional operations. In many cases the
products just crystallize directly out of the reaction mix-
ture. The side products (volatile alkyl halides) could be
easily removed by simple evaporation. It is also possible
to obtain the so-called orthogonally protected derivatives
of 1-aminoalkylphosphonates or (1-aminoalkyl)phenyl-
phosphinates.
Searching common databases, we found only one applica-
tion of dialkyl phosphonites for the synthesis of ami-
noalkyl(phenyl)phosphinates. Thai13 described the
reaction of alkanimines with diethyl phenylphosphonite
in the presence of N,N-diethylaniline hydrochloride.
There are many publications6 devoted to the preparation
of 1-(alkylamino)alkylphosphonates, but simple addition
of phosphorus compounds containing at least one H–P
Synthesis 2010, No. 14, 2437–2445 © Thieme Stuttgart · New York

PAPER
1-(Alkylamino)alkyl-Substituted Phosphorus Derivatives via Iminium Ions
2439
Table 1 Dialkyl 1-(Alkylamino)alkylphosphonates, Alkyl [1-(Alkylamino)alkyl]phenylphosphinates, and [1-(Alkylamino)alkyl]diphe-
nylphosphine Oxides
R1
N
R1
R3
R4
O
P
R3
R4
H-Cl
N
+
AlkO
P
R2
R2
– Alk-Cl
H
>90% (by NMR)
50–99% isolated
Entry
1
R1
H
R2
R3
R4
Product
1a
1b
1c
Yielda (%)
57
CPh3
CPh3
CPh3
CPh3
CPh3
CPh3
CPh3
CPh3
CPh3
CPh3
CPh3
Pr
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Ph
OEt
2
Me
Et
OEt
81
3
OEt
72
4
Pr
OEt
1d
1e
89
5
i-Pr
Bu
Ph
OEt
89
6
OEt
1f
50
7
OEt
1g
1h
1i
92b
94b
94b
~100b
94b
75c
76c
55c
69c
51c
88c
68c
81c
78c
62c
58c
74c
79
8
4-MeOC6H4
4-ClC6H4
2-MeOC6H4
4-O2NC6H4
4-MeOC6H4
Ph
OEt
9
OEt
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
OEt
1j
OEt
1k
1l
OEt
s-Bu
s-Bu
t-Bu
OEt
1m
1n
1o
1p
1q
1r
4-MeOC6H4
Ph
OEt
OEt
4-MeOC6H4
Ph
t-Bu
OEt
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CHPh2
CHPh2
CHMePh
CPh3
Pr
OEt
CHEt2
i-Pr
OEt
OEt
1s
3-pyridyl
CHEt2
Ph
OEt
1t
OEt
1u
1v
1w
2a
2b
2c
OEt
Ph
OEt
H
O(CH2)2Cl
O(CH2)2Cl
O(CH2)2Cl
O(CH2)2Cl
Ph
Ph
Ph
76c
60c
55c
80
Ph
CH2Ph
Pr
Ph
3-MeC6H4
Ph
Ph
2d
3a
3b
3c
CH2Ph
Pr
Ph
4-MeOC6H4
H
Ph
Ph
74
CPh3
Ph
Ph
79
a Isolated product (yields assayed by 31P NMR are almost quantitative).
b Crystallized after evaporation of solvent.
c Isolated also as oxalates.
Synthesis 2010, No. 14, 2437–2445 © Thieme Stuttgart · New York

2440
W. Goldeman, M. Soroka
PAPER
HCl (~0.05 mol) in Et2O. The mixture was stirred for ~2 h at this
temperature and then it was placed in the freezer (below –10 °C)
overnight. Solvent and volatile byproducts were evaporated under
vacuum (warm water bath, below 40 °C) to give a solid or oily res-
idue, which was recrystallized (hexane, 25 mL, freezer, –10 °C, 24
h). Then the product was filtered, washed with a cold hexane (3 × 5
mL) and air dried.
Noncrystallizing products were isolated as oxalates by a known3
procedure. Thus, the oily residue was dissolved in acetone (10 mL),
and a soln of oxalic acid (hydrated, 7.2 g, 0.060 mol) in acetone (30
mL) was added dropwise. The crystallizing mixture was kept in the
freezer as it described above, the product was filtered, washed with
a cold acetone (4 × 5 mL), and air dried.
NMR spectra were recorded on a Bruker Avance 300 MHz spec-
trometer. Lock and shim was performed on the deuterium signal
from CDCl3, chemical shifts were calculated from the chemical
shift of the deuterium lock and were not calibrated. FT-IR spectra
were measured on a Perkin Elmer 2000 spectrophotometer as KBr
pellets (1/200) for crystalline products or as a film for liquid prod-
ucts. Melting points were determined on the Boetius microscope
with electrical hot plate and were corrected. Since all compounds
described in this paper melted with decomposition, their melting
points are useless for their characterization. The carbonyl com-
pounds were distilled before use. All reagents and solvents were of
commercial quality. The procedures and isolations of products de-
scribed in this paper were not optimized.
Bis(2-chloroethyl) Phenylphosphonite
Diethyl [(Triphenylmethyl)amino]methylphosphonate (1a)
Yield: 57%; mp 112–114 °C (CH2Cl2–hexane) (Lit.3 115–117 °C).
PhPCl2 (8.9 g, 0.050 mol) was added dropwise to a cold soln (~0 °C)
of oxirane (4.8 g, 0.11 mol) in CH2Cl2 (30 mL) The mixture was
stirred at this temperature for ~0.5 h, then it was evaporated under
vacuum (warm water bath, below 40 °C) to give the crude product
which was used in the reaction without purification.
IR (KBr): 3278 (NH), 1245 (P=O), 1050 (P–O–C), 1025 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 1.37 (t, J = 7.05 Hz, 6 H, CH3),
1.63 (br s, 1 H, NH), 2.50 (d, J = 13.8 Hz, 2 H, CH2P), 4.20 (dq,
J = 7.0, 13.1 Hz, 4 H, CH2O), 7.19 (t, J = 7.2 Hz, 3 H, p-ArH), 7.28
(t, J = 7.2 Hz, 6 H, m-ArH), 7.47 (d, J = 7.2 Hz, 6 H, o-ArH).
N-Alkylalkanimines
N-Alkylalkanimines were prepared by modification of previously
described protocol.3 Thus, an aldehyde (0.050 mol) was added
dropwise to the soln of amine (0.050 mol) in CH2Cl2 (30 mL) at ~0
°C, then the mixture was stirred overnight at r.t. (ca. 20 °C), dried
(anhyd Na2SO4, 10 g). The Na2SO4 was removed by suction,
washed with CH2Cl2 (4 × 5 mL), and the collected filtrates were
used directly as a soln of a crude N-alkylalkanimine.
31P NMR (121 MHz, CDCl3): d = 28.5.
Anal. Calcd for C24H28NO3P: N, 3.42; P, 7.56. Found: N, 3.53; P,
7.52.
Diethyl 1-[(Triphenylmethyl)amino]ethylphosphonate (1b)
Yield: 81%; mp 140–141 °C (CH2Cl2–hexane).
IR (KBr): 3261 (NH), 1237 (P=O), 1052 (P–O–C), 1015 cm–1 (P–
O–C).
Diethyl 1-[(Triphenylmethyl)amino]ethylphosphonate (1b);
Cross-Coupling Experiment
To a cold (ca. –10 °C, ice/NaCl bath) soln of N-(triphenylmeth-
yl)ethanimine3 (5.7 g, 0.020 mol), P(OEt)3 (3.3 g, 0.020 mol), and
HP(O)(OMe)2 (2.2 g, 0.020 mol) in CH2Cl2 (40 mL) was added
dropwise cold (ca. –10 °C) HCl (~0.02 mol) in Et2O soln. The mix-
ture was stirred for ~1 h at the same temperature and then it was kept
in the freezer (below –10 °C) overnight. Then, ~0.25 mL was taken
from the mixture, evaporated to dryness in vacuo (cold water bath),
1H NMR (300 MHz, CDCl3): d = 0.35 (dd, J = 6.9, 18.3 Hz, 3 H,
CH3), 1.28 (t, J = 7.1 Hz, 6 H, CH3CH2O), 1.74 (d, J = 6.7 Hz, 1 H,
NH), 3.00–3.10 (m, 1 H, CHP), 4.23 (dq, J = 7.3, 14.6 Hz, 4 H,
CH2O), 7.19 (t, J = 7.3 Hz, 3 H, p-ArH), 7.29 (t, J = 7.3 Hz, 6 H, m-
ArH), 7.47 (d, J = 7.3 Hz, 6 H, o-ArH).
31P NMR (121 MHz, CDCl3): d = 30.2.
the residue was dissolved in CDCl3 (0.50 mL) and analyzed by 31
P
Anal. Calcd for C25H30NO3P: N, 3.31; P, 7.31. Found: N, 3.50; P,
7.17.
1
and H NMR spectroscopy. No trace of dimethyl 1-[(triphenyl-
methyl)amino]ethylphosphonate was found. The main product was
identified as diethyl 1-[(triphenylmethyl)amino]ethylphosphonate
(1b) [partially as its hydrochloride, which was confirmed by wash-
ing the sample in the NMR tube with sat. aq NaHCO3 (0.5 mL) and
measuring the NMR spectra again]. The mixture contained also un-
reacted HP(O)(OMe)2, a minor amount of methyl phosphonate, and
traces of HP(O)(OEt)2.
Diethyl 1-[(Triphenylmethyl)amino]propylphosphonate (1c)
Yield: 72%; mp 122–124 °C (CH2Cl2–hexane).
IR (KBr): 3256 (NH), 1234 (P=O), 1057 (P–O–C), 1024 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 0.58 (t, J = 7.2 Hz, 3 H, CH3),
0.65–0.87 (m, 2 H, CH2), 1.37 (t, J = 7.0 Hz, 6 H, CH3CH2O), 2.22
(d, J = 7.4 Hz, 1 H, NH), 2.93–3.05 (m, 1 H, CHP), 4.22 (dq, J = 7.3
Hz, 4 H, CH2O), 7.18 (t, J = 7.0 Hz, 3 H, p-ArH), 7.27 (t, J = 7.2 Hz,
6 H, m-ArH), 7.47 (d, J = 7.4 Hz, 6 H, ArH).
The rest of the mixture was evaporated under vacuum (warm water
bath, below 40 °C) to give an oily residue that was crystallized
(Et2O, 15 mL). The crystallizing mixture was kept in the freezer at
ca. –10 °C for ~12 h, and then the product was filtered, washed with
cold Et2O (3 × 3 mL), and dried, to give crude 1b (7.0 g, 82%). The
crude product was dissolved in CH2Cl2 (20 mL), washed with cold
sat. NaHCO3 (3 × 20 mL), then with brine (2 × 20 mL), dried (an-
hyd Na2SO4), and evaporated under vacuum (warm water bath, be-
low 40 °C) to give a pure crystalline product, which after
recrystallization (Et2O) gave an analytical sample of 1b (5.2 g,
61%) identical to that obtained using the general procedure.
31P NMR (121 MHz, CDCl3): d = 30.2.
Anal. Calcd for C26H32NO3P: N, 3.20; P, 7.08. Found: N, 3.36; P,
6.81.
Diethyl 1-[(Triphenylmethyl)amino]butylphosphonate (1d)
Yield: 89%; mp 95–97 °C (CH2Cl2–hexane).
IR (KBr): 3288 (NH), 1235 (P=O), 1053 (P–O–C), 1020 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 0.39 (t, J = 7.2 Hz, 3 H, CH3),
0.54–0.65 (m, 2 H, CH3CH2), 0.85–1.12 (m, 2 H, CHaHbCHP), 1.30
(t, J = 7.0 Hz, 6 H, CH3CH2O), 2.07 (d, J = 5.3 Hz, 1 H, NH), 2.99
(dddd, J = 7.5, 18.8, 5.3 Hz, 1 H, CHP), 4.16 (dq, J = 7.3, 14.3 Hz,
4 H, CH2O), 7.21 (t, J = 7.1 Hz, 3 H, p-ArH), 7.27 (t, J = 7.1 Hz, 6
H, m-ArH), 7.47 (d, J = 7.1 Hz, 6 H, o-ArH).
Dialkyl 1-(Alkylamino)alkylphosphonates 1, Alkyl [1-(Alkyl-
amino)alkyl]phenylphosphinates 2, and [1-(Alkylamino)alkyl]di-
phenylphosphine Oxides 3; General Procedure
To a cold (ca. –10 °C, ice/NaCl bath) soln of N-alkylalkanimine
(0.050 mol) and P(OEt)3 (0.050 mol), bis(2-chloroethyl) phe-
nylphosphonite (0.050 mol), or ethyl diphenylphosphinite (0.050
mol), in CH2Cl2 (50 mL) was added dropwise cold (ca. –10 °C) 4 M
Synthesis 2010, No. 14, 2437–2445 © Thieme Stuttgart · New York

PAPER
1-(Alkylamino)alkyl-Substituted Phosphorus Derivatives via Iminium Ions
2441
31P NMR (121 MHz, CDCl3): d = 30.1.
Anal. Calcd for C31H34NO4P: N, 2.72; P, 6.01. Found: N, 2.57; P,
6.08.
Anal. Calcd for C27H34NO3P: N, 3.10; P, 6.83. Found: N, 3.29; P,
6.80.
Diethyl (4-Chlorophenyl)[(triphenylmethyl)amino]methyl-
phosphonate (1i)
Yield: 94%; mp 177–179 °C (CH2Cl2–hexane).
IR (KBr): 3293 (NH), 1237 (P=O), 1060 (P–O–C), 1014 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 1.06 (t, J = 7.1 Hz, 3 H, CH3),
1.35 (t, J = 7.0 Hz, 3 H, CH3), 3.03 (br s, 1 H, NH), 3.51–3.61 (m,
1 H, CH2O), 3.80–3.88 (m, 1 H, CH2O), 4.11–4.23 (m, 3 H, CH2O,
CHP), 6.72 (d, J = 6.6 Hz, 1 H, m-ArH), 6.73 (d, J = 6.3 Hz, 1 H, o-
ArH), 6.86 (d, J = 8.5 Hz, 1 H, m-ArH), 6.87 (d, J = 8.5 Hz, 1 H, o-
ArH), 7.06–7.14 (m, 9 H, p-, m-ArHTr), 7.41 (d, J = 7.9 Hz, 3 H, o-
ArHTr), 7.42 (d, J = 7.9 Hz, 3 H, o-ArHTr).
Diethyl 2-Methyl-1-[(triphenylmethyl)amino]propylphos-
phonate (1e)
Yield: 89%; mp 90–92 °C (CH2Cl2–hexane).
IR (KBr): 3278 (NH), 1234 (P=O), 1058 (P–O–C), 1026 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 0.77 (d, J = 6.6 Hz, 3 H, CH3),
0.79 (d, J = 6.7 Hz, 3 H, CH3), 1.12 [m, 1 H, (CH3)2CH], 1.23 (t,
J = 7.0 Hz, 6 H, CH3CH2O), 2.57 (d, J = 6.9 Hz, 1 H, NH), 2.92 (dd,
J = 6.3, 20.9 Hz, 1 H, CHP), 3.90–4.08 (m, 4 H, CH2O), 7.17 (t,
J = 7.0 Hz, 3 H, p-ArH), 7.25 (t, J = 7.0 Hz, 6 H, m-ArH), 7.50 (d,
J = 7.4 Hz, 6 H, o-ArH).
31P NMR (121 MHz, CDCl3): d = 25.2.
31P NMR (121 MHz, CDCl3): d = 29.7.
Anal. Calcd for C30H31ClNO3P: N, 2.69; P, 5.96. Found: N, 2.83; P,
5.88.
Anal. Calcd for C27H34NO3P: N, 3.10; P, 6.83. Found: N, 2.92; P,
6.80.
Diethyl (2-Methoxyphenyl)[(triphenylmethyl)amino]methyl-
phosphonate (1j)
Yield: ~100%; mp 147–149 °C (CH2Cl2–hexane).
IR (KBr): 3290 (NH), 1234 (P=O), 1056 (P–O–C), 1027 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 1.02 (t, J = 7.0 Hz, 3 H, CH3),
1.33 (t, J = 7.0 Hz, 3 H, CH3), 2.96 (d, J = 8.6 Hz, 1 H, NH), 3.41–
3.70 (m, 1 H, CH2O), 3.51 (s, 3 H, CH3O), 3.71–3.83 (m, 1 H,
CH2O), 4.07–4.22 (m, 2 H, CH2O), 4.84 (dd, J = 8.6, 23.8 Hz, 1 H,
CHP), 6.35 (d, J = 8.2 Hz, 1 H, 3-ArH), 6.60 (t, J = 7.8 Hz, 1 H, 5-
ArH), 6.88 (t, J = 7.8 Hz, 1 H, 4-ArH), 6.97–7.10 (m, 10 H, p-, m-
ArHTr, 6-ArH), 7.47 (d, J = 7.3 Hz, 6 H, o-ArHTr).
Diethyl 1-[(Triphenylmethyl)amino]pentylphosphonate (1f)
Yield: 50%; mp 83–85 °C (hexane).
IR (KBr): 3271 (NH), 1236 (P=O), 1053 (P–O–C), 1026 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 0.64 (t, J = 7.2 Hz, 3 H, CH3),
0.71–0.80 (m, 4 H, CH3CH2CH2), 0.84–0.93 (m, 1 H, CHaHbCHP),
0.95–1.10 (m, 1 H, CHaHbCHP), 1.34 (t, J = 7.0 Hz, 6 H,
CH3CH2O), 2.15 (dd, J = 1.8, 9.0 Hz, 1 H, NH), 2.95–3.10 (m, 1 H,
CHP), 4.18 (dq, J = 7.1, 14.2 Hz, 4 H, CH2O), 7.16 (t, J = 7.2 Hz, 3
H, p-ArH), 7.25 (t, J = 7.2 Hz, 6 H, m-ArH), 7.58 (d, J = 7.4 Hz, 6
H, o-ArH).
31P NMR (121 MHz, CDCl3): d = 30.6.
31P NMR (121 MHz, CDCl3): d = 26.5.
Anal. Calcd for C28H36NO3P: N, 3.01; P, 6.65. Found: N, 3.03; P,
6.74.
Anal. Calcd for C31H34NO4P: N, 2.72; P, 6.01. Found: N, 2.90; P,
5.70.
Diethyl Phenyl[(triphenylmethyl)amino]methylphosphonate
(1g)
Yield: 92%; mp 132–134 °C (CH2Cl2–Et2O).
IR (KBr): 3286 (NH), 1238 (P=O), 1053 (P–O–C), 1026 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 1.03 (t, J = 7.0 Hz, 3 H, CH3),
1.38 (t, J = 7.0 Hz, 3 H, CH3), 3.07 (br s, 1 H, NH), 3.29–3.49 (m,
1 H, CH2O), 3.76–3.86 (m, 1 H, CH2O), 4.10–4.22 (m, 3 H, CH2O,
CHP), 6.81 (d, J = 5.2 Hz, 2 H, o-ArH), 6.91–6.94 (m, 3 H, p-, m-
ArH), 7.06 (t, J = 7.1 Hz, 3 H, p-ArHTr), 7.11 (t, J = 7.1 Hz, 6 H, m-
ArHTr), 7.46 (d, J = 7.7 Hz, 6 H, o-ArH).
Diethyl (4-Nitrophenyl)[(triphenylmethyl)amino]methylphos-
phonate (1k)
Yield: 94%; mp 183–186 °C (CH2Cl2–hexane).
IR (KBr): 3289 (NH), 1517 (NO2), 1346 (NO2), 1238 (P=O), 1054
(P–O–C), 1023 cm–1 (P–O–C).
1H NMR (300 MHz, CDCl3): d = 1.09 (t, J = 7.0 Hz, 3 H, CH3),
1.36 (t, J = 7.1 Hz, 3 H, CH3), 3.21 (d, J = 8.0 Hz, 1 H, NH), 3.62–
3.75 (m, 1 H, CH2O), 3.84–3.98 (m, 1 H, CH2O), 4.10–4.25 (m, 2
H, CH2O), 4.35 (dd, J = 8.0, 24.9 Hz, 1 H, CHP), 6.96 (d, J = 8.8
Hz, 1 H, o-ArH), 6.97 (d, J = 8.8 Hz, 1 H, o-ArH), 7.02–7.13 (m, 9
H, p-, m-ArHTr), 7.41 (d, J = 8.4 Hz, 3 H, o-ArHTr), 7.42 (d, J = 8.4
Hz, 3 H, o-ArHTr), 7.74 (d, J = 8.8 Hz, 2 H, m-ArH).
31P NMR (121 MHz, CDCl3): d = 25.4.
31P NMR (121 MHz, CDCl3): d = 24.2.
Anal. Calcd for C30H32NO3P: N, 2.88; P, 6.65. Found: N, 3.00; P,
6.38.
Anal. Calcd for C30H31N2O5P: N, 5.28; P, 5.84. Found: N, 5.50; P,
6.12.
Diethyl (4-Methoxyphenyl)[(triphenylmethyl)amino]methyl-
phosphonate (1h)
Yield: 94%; mp 157–159 °C (CH2Cl2–hexane).
IR (KBr): 3289 (NH), 1239 (P=O), 1050 (P–O–C), 1028 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 1.05 (t, J = 7.0 Hz, 3 H, CH3),
1.38 (t, J = 7.0 Hz, 3 H, CH3), 2.97 (br s, 1 H, NH), 3.41–3.50 (m,
1 H, CH2O), 3.70 (s, 3 H, CH3O), 3.77–3.85 (m, 1 H, CH2O), 4.10–
4.21 (m, 3 H, CH2O, CHP), 6.46 (d, J = 8.3 Hz, 2 H, m-ArH), 6.72
(d, J = 8.3 Hz, 2 H, o-ArH), 7.06 (t, J = 6.9 Hz, 3 H, p-ArHTr), 7.12
(t, J = 6.9 Hz, 6 H, m-ArHTr), 7.46 (d, J = 7.0 Hz, 6 H, o-ArHTr).
Diethyl (4-Methoxyphenyl)(propylamino)methylphosphonate
Oxalate (1l·C2H2O4)
Yield: 75%; mp 124–126 °C.
1H NMR (300 MHz, D2O): d = 0.79 (t, J = 7.3 Hz, 3 H, CH3), 1.13
(t, J = 6.9 Hz, 3 H, CH3CH2O), 1.24 (t, J = 6.9 Hz, 3 H, CH3CH2O),
1.42–1.75 (m, 2 H, CH2CH2N), 2.85 (t, J = 6.6 Hz, 2 H, CH2N),
3.78 (s, 3 H, CH3O), 3.83–4.00 (m, 1 H, CH2O), 4.01–4.07 (m, 1 H,
CH2O), 4.02–4.20 (m, 2 H, CH2O), 4.78 (d, J = 18.0 Hz, 1 H, CHP),
7.03 (d, J = 8.3 Hz, 2 H, m-ArH), 7.41 (d, J = 8.3 Hz, 2 H, o-ArH).
31P NMR (121 MHz, D2O): d = 18.3.
31P NMR (121 MHz, CDCl3): d = 25.5.
Synthesis 2010, No. 14, 2437–2445 © Thieme Stuttgart · New York

2442
W. Goldeman, M. Soroka
PAPER
Anal. Calcd for C15H26NO4P·C2H2O4: N, 3.46; P, 7.64. Found: N,
3.56; P, 7.40.
Hz, 1 H, PhCHaHb), 4.50 (d, J = 18.1 Hz, 1 H, CHP), 7.10 (d, J = 6.0
Hz, 2 H, o-ArH), 7.20–7.28 (m, 6 H, ArH), 7.33 (d, J = 4.3 Hz, 2 H,
o-ArH).
Diethyl (1-Methylpropylamino)phenylmethylphosphonate
Oxalate (1m·C2H2O4)
Yield: 76%; mixture of 2 diastereomers, ratio 57:43; mp not deter-
31P NMR (121 MHz, D2O): d = 18.1.
Anal. Calcd for C18H24NO3P·C2H2O4: N, 3.31; P, 7.32. Found: N,
3.40; P, 7.08.
mined.
1H NMR (300 MHz, D2O): d = 0.77 (t, J = 7.3 Hz, 3 H,
CH3CH2CH), 1.10 (t, J = 7.0 Hz, 3 H, CH3CH2O), 1.17 (t, J = 7.0
Hz, 3 H, CH3CH2O), 1.23 (d, J = 6.8 Hz, 3 H, CH3CH), 1.35–1.57
(m, 1 H, CHaHbCH), 1.64–1.85 (m, 1 H, CHaHbCH), 3.09–3.17 (m,
1 H, CHN), 3.83–3.94 (m, 1 H, CH2O), 3.95–4.04 (m, 1 H, CH2O),
4.05–4.16 (m, 2 H, CH2O), 4.93 (d, J = 18.8 Hz, 1 H, CHP), 7.46 (s,
5 H, Ph).
Diethyl 1-(Benzylamino)-2-ethylbutylphosphonate Oxalate
(1r·C2H2O4)
Yield: 68%; mp 116–117 °C.
1H NMR (300 MHz, D2O): d = 0.60 (t, J = 7.2 Hz, 3 H, CH3), 0.80
(t, J = 7.1 Hz, 3 H, CH3), 1.21–1.55 (m, 4 H, CH3CH2), 1.29 (t,
J = 7.0 Hz, 3 H, CH3CH2O), 1.33 (t, J = 7.0 Hz, 3 H, CH3CH2O),
1.67–1.74 (m, 1 H, CH3CH2CH), 3.44 (dd, J = 16.5, 2.4 Hz, 1 H,
CHP), 4.10–4.25 (m, 4 H, CH2O), 4.29 (d, J = 13.3 Hz, 1 H, Ph-
CHaHb), 4.42 (d, J = 13.3 Hz, 1 H, PhCHaHb), 7.45 (s, 5 H, Ph).
31P NMR (121 MHz, D2O): d = 18.4 (57%), 18.50 (43%).
Anal. Calcd for C15H26NO3P·C2H2O4: N, 3.60; P, 7.84. Found: N,
3.68; P, 7.84.
31P NMR (121 MHz, D2O): d = 21.4.
Anal. Calcd for C17H30NO3P·C2H2O4·2 H2O: N, 3.09; P, 6.83.
Found: N, 3.01; P, 6.32.
Diethyl (4-Methoxyphenyl)(1-methylpropylamino)methylphos-
phonate Oxalate (1n·C2H2O4)
Yield: 55%; mixture of 2 diastereomers in molar ratio 53:47; mp not
determined.
Diethyl 1-(Benzylamino)-2-methylpropylphosphonate Oxalate
(1s·C2H2O4)
Yield: 81%; mp not determned.
1H NMR (300 MHz, D2O): d = 0.90 (d, J = 7.1 Hz, 3 H, CH3), 0.97
(d, J = 7.3 Hz, 3 H, CH3), 1.18 (t, J = 7.2 Hz, 3 H, CH3CH2O), 1.24
(t, J = 7.0 Hz, 3 H, CH3CH2O), 2.21–2.34 (m, 1 H, CH), 3.33 (dd,
J = 4.7, 15.7 Hz, 1 H CHP), 3.92–4.21 (m, 5 H, CH2O, NCHaHb),
4.30 (d, J = 13.3 Hz, 1 H, NCHaHb), 7.35 (s, 5 H, Ph).
1H NMR (300 MHz, D2O): d = 0.75 (t, J = 7.2 Hz, 3 H,
CH3CH2CH), 1.08 (t, J = 7.0 Hz, 3 H, CH3CH2O), 1.15 (t, J = 7.0
Hz, 3 H, CH3CH2O), 1.21 (d, J = 6.8 Hz, 3 H, CH3CH), 1.29–1.59
(m, 1 H, CHaHbCH), 1.66–1.76 (m, 1 H, CHaHbCH), 3.04–3.14 (m,
1 H, CHN), 3.73 (s, 3 H, CH3O), 3.80–3.88 (m, 1 H, CH2O), 3.94–
4.02 (m, 1 H, CH2O), 4.03–4.10 (m, 2 H, CH2O), 4.85 (d, J = 18.8
Hz, 1 H, CHP), 6.99 (d, J = 8.1 Hz, 2 H, m-ArH), 7.41 (d, J = 8.1
Hz, 2 H, o-ArH).
31P NMR (121 MHz, D2O): d = 20.9.
31P NMR (121 MHz, D2O): d = 18.5 (53%), 18.6 (47%).
Anal. Calcd for C15H26NO3P·C2H2O4: N, 3.60; P, 7.95. Found: N,
3.45; P, 7.55.
Anal. Calcd for C16H28NO4P·C2H2O4: N, 3.34; P, 7.38. Found: N,
3.22; P, 6.96.
Diethyl (Benzylamino)(pyridin-3-yl)methylphosphonate
Oxalate (1t·C2H2O4)
Yield: 78%; mp 135–138 °C.
Diethyl (tert-Butylamino)phenylmethylphosphonate Oxalate
(1o·C2H2O4)
1H NMR (300 MHz, D2O): d = 1.16 (t, J = 7.0 Hz, 3 H, CH3CH2O),
1.22 (t, J = 7.0 Hz, 3 H, CH3CH2O), 3.91–4.18 (m, 6 H, CH2O,
PhCH2), 4.77 (d, J = 20.3 Hz, 1 H, CHP), 7.12–7.25 (m, 2 H, ArH),
7.26–7.35 (m, 3 H, ArH), 7.92 (dd, J = 5.5, 7.7 Hz, 1 H, H5Py), 8.43
(d, J = 7.7 Hz, 1 H, H4Py), 8.65 (s, 1 H, H2Py), 8.70 (d, J = 5.5 Hz, 1
H, H6Py).
Yield: 69%; mp 120–121 °C.
1H NMR (300 MHz, CDCl3): d = 1.39 (t, J = 7.0 Hz, 3 H,
CH3CH2O), 1.50 (t, J = 7.0 Hz, 3 H, CH3CH2O), 1.53 (s, 9 H, t-Bu),
3.89–4.05 (m, 1 H, CH2O), 4.17–4.40 (m, 3 H, CH2O), 4.68 (d,
J = 21.6 Hz, 1 H, CHP), 7.61–7.70 (m, 3 H, p-, m-ArH), 7.85 (d,
J = 5.9 Hz, 2 H, o-ArH), 8.68 (br s, 3 H, NH2 , COOH).
31P NMR (121 MHz, CDCl3): d = 17.7.
+
31P NMR (121 MHz, D2O): d = 19.1.
Anal. Calcd for C17H23N2O3P·C2H2O4·2 H2O: N, 6.08; P, 6.73.
Found: N, 6.73; P, 6.28.
Anal. Calcd for C15H26NO3P·C2H2O4: N, 3.60; P, 7.95. Found: N,
3.88; P, 7.66.
Diethyl 1-[(Diphenylmethyl)amino]-2-ethylbutylphosphonate
Oxalate (1u·C2H2O4)
Yield: 62%; mp not determined.
Diethyl (tert-Butylamino)(4-methoxyphenyl)methylphos-
phonate Oxalate (1p·C2H2O4)
Yield: 51%; mp not determined.
1H NMR (300 MHz, CDCl3): d = 0.53 (t, J = 7.1 Hz, 3 H,
CH3CH2O), 0.74 (t, J = 7.0 Hz, 3 H, CH3CH2O), 1.25 (t, J = 7.0 Hz,
3 H, CH3), 1.29 (t, J = 7.1 Hz, 3 H, CH3), 1.30–1.51 [m, 5 H,
(CH2)2CH], 3.00 (d, J = 15.2 Hz, 1 H, CHP), 4.09 (dq, J = 7.1, 14.7
Hz, 4 H, CH2O), 5.27 (s, 1 H, NCH), 7.04 (br s, 3 H, NH2 , COOH),
7.07–7.26 (m, 6 H, p-, m-ArH), 7.35 (d, J = 7.3 Hz, 2 H, o-ArH),
7.41 (d, J = 7.3 Hz, 2 H, o-ArH).
1H NMR (300 MHz, CDCl3): d = 1.03 (t, J = 7.2 Hz, 3 H,
CH3CH2O), 1.20 (t, J = 7.2 Hz, 3 H, CH3CH2O), 1.40 (s, 9 H, t-Bu),
3.75 (s, 3 H, OCH3), 3.80–3.84 (m, 1 H, CH2O), 3.92–4.01 (m, 1 H,
CH2O), 4.11 (dq, J = 7.2 Hz, J = 14.8 Hz, 2 H, CH2O), 4.88 (d,
J = 20.5 Hz, 1 H, CHP), 7.00 (d, J = 8.6 Hz, 2 H, m-ArH), 7.45 (d,
J = 7.0 Hz, 2 H, o-ArH).
+
31P NMR (121 MHz, CDCl3): d = 18.5.
31P NMR (121 MHz, CDCl3): d = 29.2.
Diethyl (Benzylamino)phenylmethylphosphonate Oxalate
(1q·C2H2O4)
Yield: 88%; mp 132–133 °C.
1H NMR (300 MHz, D2O): d = 0.96 (t, J = 7.0 Hz, 3 H, CH3), 1.09
(t, J = 7.0 Hz, 3 H, CH3), 3.67–3.79 (m, 1 H, CH2O), 3.81–3.90 (m,
1 H, CH2O), 3.90–4.10 (m, 3 H, CH2O, PhCHaHb), 4.09 (d, J = 13.3
Diethyl [(Diphenylmethyl)amino]phenylmethylphosphonate
Oxalate (1v·C2H2O4)
Yield: 58%; mp not determined.
1H NMR (300 MHz, D2O): d = 1.01 (t, J = 7.0 Hz, 3 H, CH3), 1.30
(t, J = 7.0 Hz, 3 H, CH3), 3.61–3.73 (m, 1 H, CH2O), 3.80–3.92 (m,
Synthesis 2010, No. 14, 2437–2445 © Thieme Stuttgart · New York

PAPER
1-(Alkylamino)alkyl-Substituted Phosphorus Derivatives via Iminium Ions
2443
1 H, CH2O), 3.86 (d, J = 22.4, 1 H, CHP), 4.05–4.23 (m, 2 H,
2-Chloroethyl [(3-Methylphenyl)(propylamino)methyl]phe-
CH2O), 4.62 (s, 1 H, NCH), 7.10–7.28 (m, 15 H, ArH).
nylphosphinate (2d)
Yield: 55%; mixture of 2 diastereomers, ratio 70:30; mp not deter-
mined.
31P NMR (121 MHz, D2O): d = 24.8.
Diethyl Phenyl(1-phenylethylamino)methylphosphonate
Oxalate (1w·C2H2O4)
Yield: 74%; mixture of 2 diastereomers, ratio 67:33; mp not deter-
mined.
1H NMR (300 MHz, D2O): d = 0.98 (t, J = 7.0 Hz, 6 H, CH3CH2O),
1.14 (t, J = 7.0 Hz, 6 H, CH3CH2O), 1.50 (d, J = 6.1 Hz, 6 H, CH3),
3.60–3.77 (m, 2 H, CH2O), 3.80–3.95 (m, 2 H, CH2O), 3.90–4.15
(m, 4 H, CH2O), 4.17 (d, J = 18.4 Hz, 1 H, CHP; diastereomer A),
4.19 (q, J = 6.1 Hz, 1 H, CHCH3; diastereomer A), 4.48 (d, J = 17.9
Hz, 1 H, CHP; diastereomer B), 4.50 (q, J = 6.1 Hz, 1 H, CHCH3;
diastereomer B), 7.15–7.45 (m, 20 H, ArH).
Crude oxalate was dissolved in H2O, neutralized with Na2CO3, ex-
tracted with CH2Cl2 and dried (Na2SO4). The soln was evaporated
to dryness and crystallized (Et2O).
IR (KBr): 3258 (NH), 1251 (P=O), 1065 (P–O–C), 1029 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 0.66 (t, J = 7.4 Hz, 3 H, CH3; dia-
stereomer A), 0.72 (t, J = 7.5 Hz, 3 H, CH3; diastereomer B), 1.38–
1.60 (m, 4 H, CH3CH2; diastereomer A + B), 2.04 (s, 3 H, CH3; dia-
stereomer B), 2.12 (s, 3 H, CH3; diastereomer A), 2.80 (t, J = 8.0
Hz, 2 H, NCH2; diastereomer A), 2.86 (t, J = 8.0 Hz, 2 H, NCH2;
diastereomer B), 3.61 (ddd, J = 1.9, 6.1, 6.1 Hz, 2 H, CH2Cl; dia-
stereomer A), 3.68 (ddd, J = 1.7, 5.9, 5.9 Hz, 2 H, CH2Cl; diastereo-
mer B), 4.03–4.18 (m, 2 H, CH2O), 4.22–4.30 (m, 2 H, CH2O), 4.81
(d, J = 12.5 Hz, 1 H, CHP; diastereomer A), 4.89 (d, J = 11.8 Hz, 1
H, CHP; diastereomer B), 6.93 (s, 1 H, o-ArH; diastereomer B),
7.00 (s, 1 H, o-ArH; diastereomer A), 7.05 (d, J = 5.2 Hz, 1 H, ArH;
diastereomer B), 7.16 (d, J = 4.8 Hz, 1 H, ArH; diastereomer A),
7.28–7.47 (m, 13 H, ArH), 7.53–7.58 (m, 1 H, ArH).
31P NMR (121 MHz, D2O): d = 18.1 (67%), 18.2 (33%).
Anal. Calcd for C19H26NO3P·C2H2O4: N, 3.20; P, 7.01. Found: N,
3.45; P, 6.85.
2-Chloroethyl Phenyl{[(triphenylmethyl)amino]methyl}phos-
phinate (2a)
Yield: 79%; mp 142–146 °C.
31P NMR (121 MHz, CDCl3): d = 39.1 (70%), 41.4 (30%).
IR (KBr): 3255 (NH), 1231 (P=O), 1039 (P–O–C), 1011 cm–1 (P–
O–C).
1H NMR (300 MHz, CDCl3): d = 1.96 (br s, 1 H, NH), 2.58 (dd,
J = 4.4, 11.0 Hz, 2 H, CH2P), 3.60 (ddd, J = 2.1, 7.7, 7.7 Hz, 2 H,
CH2Cl), 3.98–4.10 (m, 1 H, OCHaHb), 4.15–4.26 (m, 1 H,
OCHaHb), 7.06–7.16 (m, 9 H, p-, m-ArHTr), 7.22 (d, J = 6.6 Hz, 6
H, o-ArHTr), 7.49–7.62 (m, 3 H, ArH), 7.82–7.91 (m, 2 H, ArH).
[(Benzylamino)phenylmethyl]diphenylphosphine Oxide (3a)
Yield: 80%; mp 140–143 °C.
IR (KBr): 3444 (NH), 1212 (P=O), 1176 (P=O), 1069 (P–O–C),
1028 cm–1 (P–O–C).
1H NMR (300 MHz, CDCl3): d = 2.65 (br s, 1 H, NH), 3.51 (d,
J = 13.5 Hz, 1 H, PhCHaHb), 3.85 (d, J = 13.5 Hz, 1 H, PhCHaHb),
4.38 (d, J = 10.8 Hz, 1 H, CHP), 7.09–7.30 (m, 12 H, ArH), 7.37–
7.59 (m, 6 H, ArH), 7.75–7.91 (m, 2 H, ArH).
31P NMR (121 MHz, CDCl3): d = 49.2.
Anal. Calcd for C28H27ClNO2P: N, 2.94; P, 6.51; Cl, 7.45. Found:
N, 3.03; P, 6.30; Cl, 6.80.
31P NMR (121 MHz, CDCl3): d = 38.5.
2-Chloroethyl Phenyl[phenyl(propylamino)methyl]phosphi-
nate Oxalate (2b·C2H2O4)
Anal. Calcd for C26H24NOP: N, 3.52; P, 7.79. Found: N, 3.66; P,
7.60.
Yield: 76%; mixture of 2 diastereomers, ratio 50:50; mp not deter-
mined.
[(4-Methoxyphenyl)(propylamino)methyl]diphenylphosphine
Oxide (3b)
Yield: 74%; mp 138–141 °C.
1H NMR (300 MHz, CDCl3): d = 0.60 (t, J = 7.0 Hz, 3 H, CH3; dia-
stereomer A), 0.66 (t, J = 7.3 Hz, 3 H, CH3; diastereomer B), 1.27–
1.68 (m, 4 H, CH3CH2; diastereomer A + B), 2.75 (t, J = 8.3 Hz, 2
H, NCH2; diastereomer A), 2.87 (t, J = 8.3 Hz, 2 H, NCH2; diaste-
reomer B), 3.55 (t, J = 7.5 Hz, 2 H, CH2Cl; diastereomer A), 3.60–
3.71 (m, 2 H, CH2Cl; diastereomer B), 3.94–4.07 (m, 3 H, CH2O),
4.08–4.40 (m, 1 H, CH2O), 4.83 (d, J = 12.3 Hz, 1 H, CHP; diaste-
reoisomer A), 4.92 (d, J = 11.8 Hz, 1 H, CHP; diastereomer B),
7.05–7.50 (m, 20 H, ArH).
IR (KBr): 3334 (NH), 1251 (P=O), 1175 (P=O), 1069 (P–O–C),
1034 cm–1 (P–O–C).
1H NMR (300 MHz, CDCl3): d = 0.81 (t, J = 7.4 Hz, 3 H, CH3),
1.41 (sextet, J = 7.3 Hz, 2 H, CH2), 1.88 (br s, 1 H, NH), 2.37 (dt,
J = 7.3, 11.3 Hz, 1 H, NCHaHb), 2.53 (dt, J = 7.3, 11.3 Hz, 1 H,
NCHaHb), 3.76 (s, 3 H, CH3O), 4.42 (d, J = 10.9 Hz, 1 H, CHP),
6.73 (d, J = 8.6 Hz, 2 H, m-ArH), 7.05 (d, J = 8.6 Hz, 1 H, o-ArH),
7.06 (d, J = 8.6 Hz, 1 H, o-ArH), 7.30–7.35 (m, 2 H, ArH), 7.40–
7.49 (m, 3 H, ArH), 7.52–7.61 (m, 3 H, ArH), 7.82–7.89 (m, 2 H,
ArH).
31P NMR (121 MHz, D2O): d = 41.2 (50%), 39.0 (50%).
2-Chloroethyl [(Benzylamino)phenylmethyl]phenylphosphi-
nate Oxalate (2c·C2H2O4)
Yield: 60%; mixture of 2 diastereomers in molar ratio 62:38; mp not
31P NMR (121 MHz, CDCl3): d = 37.8.
Anal. Calcd for C23H26NO2P: N, 3.69; P, 8.16. Found: N, 3.70; P,
7.92.
determined.
1H NMR (300 MHz, CDCl3): d = 3.53 (t, J = 6.0 Hz, 2 H, CH2Cl;
diastereomer A), 3.61–3.66 (m, 2 H, CH2Cl; diastereomer B), 3.93
(d, J = 13.5 Hz, 1 H, PhCHaHb; diastereomer A), 3.96–4.10 (m, 4 H,
CH2O, PhCHaHb diastereomer A), 4.09 (d, J = 13.5 Hz, 1 H, Ph-
CHaHb; diastereomer B), 4.17–4.32 (m, 1 H, CH2O), 4.20 (d,
J = 13.5 Hz, 1 H, PhCHaHb; diastereomer B), 4.59 (d, J = 12.3 Hz,
1 H, CHP; diastereomer A), 4.73 (d, J = 11.9 Hz, 1 H, CHP; diaste-
reomer B), 7.00–7.55 (m, 30 H, ArH).
Diphenyl{[(triphenylmethyl)amino]methyl}phosphine Oxide
(3c)
Yield: 79%; mp 192–194 °C.
IR (KBr): 3322 (NH), 1229 (P=O), 1182 (P=O), 1069, 1034 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.29 (t, J = 7.5 Hz, 1 H, NH),
3.00 (dd, J = 7.5, 16.2 Hz, 2 H, CH2P), 7.14–7.24 (m, 9 H, p-, m-
ArHTr), 7.32 (d, J = 7.7 Hz, 6 H, o-ArHTr), 7.47–7.59 (m, 6 H, ArH),
7.70–7.77 (m, 4 H, ArH).
31P NMR (121 MHz, D2O): d = 41.3 (62%), 38.8 (38%).
31P NMR (121 MHz, CDCl3): d = 37.1.
Synthesis 2010, No. 14, 2437–2445 © Thieme Stuttgart · New York

2444
W. Goldeman, M. Soroka
PAPER
and dialkyl phosphonates in one pot, for examples see:
(k) Ivanova, Zh. M.; Kim, T. V.; Suvalova, E. A.; Boldeskul,
I. E.; Gololobov, Yu. G. Zh. Obshch. Khim. 1976, 46, 236;
Chem. Abstr. 1976, 85, 21540. (l) Burpitt, R. D.; Goodlett,
V. W. J. Org. Chem. 1965, 30, 4307. (m) Gancarz, R.
Tetrahedron 1995, 51, 10627. (n) Gancarz, R.; Gancarz, I.;
Walkowiak, U. Phosphorus, Sulfur Silicon Relat. Elem.
1995, 104, 45.
Anal. Calcd for C32H28NOP: N, 2.96; P, 6.54. Found: N, 2.70; P,
6.66.
Acknowledgment
Financial support of our research by Polish Taxpayers is apprecia-
ted. We thank Mrs Czesława Andrzejewska for elemental analyses,
Mrs Elżbieta Mróź for recording IR spectra, and Mr Rafał Kozicki
and Mr Paweł Dąbrowski for measuring NMR spectra.
(7) The 1H NMR study of dialkyl phosphonates confirmed
finally that these compounds exist as non-nucleophilic
phosphonate (so-called ‘keto’) tautomers, since the presence
of nucleophilic dialkyl phosphite tautomers was not found:
see (a) Bailey, W. J.; Fox, R. B. J. Org. Chem. 1963, 28, 531;
and references cited therein. The properties of the dialkyl
phosphonates were reviewed by: (b) Doak, G. O.;
Freedman, L. D. Chem. Rev. 1961, 61, 31.
(8) Pudovik, A. N.; Pudovik, M. A. Zh. Obshch. Khim. 1969, 39,
1645; Chem. Abstr. 1969, 71, 91592.
(9) Zefirov, N. S.; Matveeva, E. D. ARKIVOC 2008, (i), 1; and
references cited therein. The catalytic Kabachnik–Fields
reaction was reviewed in this paper.
(10) Shono, T.; Matsumura, Y.; Tsubata, K. Tetrahedron Lett.
1981, 22, 3249.
(11) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner,
H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401.
(12) (a) Corcoran, R. C.; Green, J. M. Tetrahedron Lett. 1990, 31,
6827. (b) Maury, C.; Gharbaoui, T.; Royer, J.; Husson, H.-P.
J. Org. Chem. 1996, 61, 3687.
References and Notes
(1) Goldeman, W.; Soroka, M. Synthesis 2006, 3019.
(2) This statement is rather intuitive because there is no way to
have the imine and the corresponding iminium salts exactly
in the same reaction environment. However, experiments ‘in
silico’ indicated that the iminium ions have a lower barrier
than the corresponding imines. See for example:
(a) Tomoda, S.; Senju, T.; Kawamura, M.; Ikeda, T. J. Org.
Chem. 1999, 64, 5396. (b) Iafe, R. G.; Houk, K. N. J. Org.
Chem. 2008, 73, 2679. Also the conclusions reached from
crystallographic data are similar. See for example:
(c) Childs, R. F.; Shaw, G. S.; Lock, C. J. L. J. Am. Chem.
Soc. 1989, 111, 5424.
(3) Soroka, M.; Zygmunt, J. Synthesis 1988, 370.
(4) Kowalik, J.; Kupczyk-Subotkowska, L.; Mastalerz, P.
Synthesis 1981, 57.
(5) When our work was finished Metlushka et al. described an
addition of trialkyl phosphites into Betti bases in the
presence of TFA. We would like to thank a referee for this
reference: Metlushka, K. E.; Kashemirov, B. A.; Zheltukhin,
V. F.; Sadkova, D. N.; Büchner, B.; Hess, C.; Kataeva, O.
N.; McKenna, C. E.; Alfonsov, V. A. Chem. Eur. J. 2009,
15, 6718.
(6) Searching common databases gives a few hundred
publications concerning aminophosphonates, more than
three hundred 1-(alkylamino)alkylphosphonates, and about
150 papers describing their synthesis and properties. Since
citation of all of them in this short article is inappropriate, we
cite here only these papers that are strongly connected to our
work. First, general methods of synthesis of these
(13) Thai, A. Tap Chi Hoa Hoc 1977, 15, 18; Chem. Abstr. 1979,
90, 152289.
(14) In 1953, Pudovik reported an addition of alkyl phosphonites
[H-P(O)(R1)OR2] to alkanimines, and described the
preparation of eight new alkyl [1-(alkylamino)alkyl]phenyl-
phosphinates: (a) Pudovik, A. N. Dokl. Akad. Nauk SSSR
1953, 92, 773; Chem. Abstr. 1955, 49, 15792. The same
reaction was later described by others: (b) Rohovec, J.;
Vojtisek, P.; Lukes, I. Phosphorus, Sulfur Silicon Relat.
Elem. 1999, 148, 79. (c) Kabachnik, M. M.; Ternovskaya,
T. N.; Zobnina, E. V.; Beletskaya, I. P. Russ. J. Org. Chem.
(Engl. Transl.) 2002, 38, 480; Chem. Abstr. 2002, 137,
370153; see also ref. 6h. (d) Szabo, A.; Jaszay, Z. M.;
Hegedus, L.; Toke, L.; Petnehazy, I. Tetrahedron Lett. 2003,
44, 4603. (e) Szabo, A.; Petnehazy, I.; Jaszay, Z. M.
Heteroat. Chem. 2003, 14, 235. (f) Bobrikova, A. A.;
Koroteev, M. P.; Stash, A. I.; Bel’skii, V. K.; Nifant’ev, E.
E. Russ. J. Org. Chem. (Engl. Transl.) 2008, 44, 1150;
Chem. Abstr. 2008, 150, 515386. Instead of alkanimine
Issleib et al. and Solodenko et al. used 1,3,5-trialkyltria-
zanes: (g) Issleib, K.; Moegelin, W.; Balszuweit, A.; Thust,
U.; Guenther, E.; Pallas, M. DD 205167, 1983; Chem. Abstr.
1984, 101, 55339. (h) Issleib, K.; Moegelin, W. Synth.
React. Inorg. Met.-Org. Chem. 1986, 16, 645.
compounds based on the addition of dialkyl phosphonates to
alkanimines was described by Pudovik and co-workers and
independently by Fields in 1952: (a) Pudovik, A. N. Dokl.
Akad. Nauk SSSR 1952, 83, 865; Chem. Abstr. 1953, 47,
25297. (b) Pudovik, A. N.; Korchemkina, M. V. Izv. Akad.
Nauk SSSR, Ser. Khim. 1952, 831; Chem. Abstr. 1954, 48,
24762. (c) Pudovik, A. N.; Korchemkina, M. V. Izv. Akad.
Nauk SSSR, Ser. Khim. 1952, 940; Chem. Abstr. 1953, 47,
61788. (d) Fields, J. J. Am. Chem. Soc. 1952, 74, 1528.
More recently see, for example: (e) Pak, V. D.; Kozlov,
N. S.; Balyakova, I. A.; Gartmann, G. A. Zh. Obshch. Khim.
1976, 46, 1012; Chem. Abstr. 1976, 85, 108711. (f) Pak,
V. D.; Gartman, G. A.; Yaganova, N. N.; Neifel’d, P. G.
Zh. Obshch. Khim. 1998, 68, 1930; Chem. Abstr. 1999, 131,
73260. (g) Harger, M. J. P.; Williams, A. J. Chem. Soc.,
Perkin Trans. 1 1989, 563. (h) Kabachnik, M. M.;
Ternovskaya, T. N.; Zobnina, E. V.; Beletskaya, I. P. Zh.
Org. Khim. 2002, 38, 504; Chem. Abstr. 2002, 138, 24766.
(i) Kabachnik, M. M.; Ternovskaya, T. N.; Zobnina, E. V.;
Beletskaya, I. P. Zh. Org. Khim. 2002, 38, 508; Chem. Abstr.
2002, 138, 24766. (j) Kabachnik, M. M.; Zobnina, E. V.;
Beletskaya, I. P. Zh. Org. Khim. 2005, 41, 517; Chem. Abstr.
2005, 144, 350758 . The reaction was successfully
improved by mixing aldehydes or ketones with alkylamines
(i) Solodenko, V. A.; Kukhar, V. P. Zh. Obshch. Khim. 1989,
59, 2684; Chem. Abstr. 1990, 113, 24475. Also an addition
of silylated phosphonites to the alkanimines was described:
(j) Afarinkia, K.; Cadogan, J. I. G.; Rees, C. W. Synlett 1990,
415. (k) Afarinkia, K.; Rees, C. W.; Cadogan, J. I. G.
Tetrahedron 1990, 46, 7175. (l) Afarinkia, K.; Cadogan, J.
I. G.; Rees, C. W. Synlett 1992, 124. Finally, the so-called
3CC reaction (Kabachnik reaction) was also reported:
(m) Duan, J.; Yu, J.; Liu, X.; Xiang, J. Hecheng Huaxue
2006, 14, 588; Chem. Abstr. 2007, 147, 72830.
Representative (1-aminoalkyl)phenylphosphinic acids were
also prepared directly from PhPCl2: (n) Oleksyszyn, J.
Synthesis 1980, 722.
(15) [1-(Alkylamino)alkyl]diphenylphosphine oxides were
mentioned in the literature, and also in this case, the most
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PAPER
1-(Alkylamino)alkyl-Substituted Phosphorus Derivatives via Iminium Ions
2445
frequently employed method was a simple addition of
(17) (a) Gilmore, W. F.; McBride, M. A. J. Am. Chem. Soc. 1972,
94, 4361. (b) Głowiak, T.; Sawka-Dobrowolska, W.;
Kowalik, J.; Mastalerz, P.; Soroka, M.; Zoń, J. Tetrahedron
Lett. 1977, 18, 3965.
(18) (a) Łukszo, J.; Tyka, R. Synthesis 1977, 239. (b) Łukszo, J.;
Tyka, R. Pol. J. Chem. 1978, 52, 321. (c) Łukszo, J.; Tyka,
R. Pol. J. Chem. 1978, 52, 959. (d) Łukszo, J.; Kowalik, J.;
Mastalerz, P. Chem. Lett. 1978, 1103.
(19) (a) Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. J. Chem.
Soc., Perkin Trans. 1 1984, 2845. (b) Issleib, K.; Doepfer,
K. P.; Balszuweit, A. Z. Naturforsch., B 1981, 36, 1392.
(20) (a) Moedritzer, K. Synth. React. Inorg. Met.-Org. Chem.
1972, 2, 317. (b) Zoń, J.; Mastalerz, P. Rocz. Chem. 1976,
50, 1403. (c) Hoffmann, H.; Foerster, H. Monatsh. Chem.
1968, 99, 380. (d) Kreutzkamp, N.; Storck, K.
diphenylphosphine oxide to the alkanimines. For examples:
see refs. 6h, 14f, and: (a) Pudovik, A. N.; Batyeva, E. S. Izv.
Akad. Nauk SSSR, Ser. Khim. 1968, 2391; Chem. Abstr.
1969, 71, 3438. (b) Messinger, P. Arch. Pharm. (Weinheim,
Ger.) 1971, 304, 842. (c) Tyka, R. Pr. Nauk. Inst. Chem.
Org. Fiz. Politech. Wroc. 1972, 4, 54; Chem. Abstr. 1975,
82, 98120. (d) Sukale, S.; Niclas, H. J.; Richter, H. J.;
Zoelch, L. DD 234869, 1986; Chem. Abstr. 1986, 105,
227005. (e) Niclas, H. J.; Sukale, S.; Richter, H. J. Z. Chem.
1985, 25, 368. (f) Rohovec, J.; Vojtisek, P.; Lukes, I.
Phosphorus, Sulfur Silicon Relat. Elem. 1999, 148, 79.
(g) Yamakoshi, K.; Harwood, S. J.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 1999, 40, 2565. (h) Boduszek, B. Synth.
Commun. 2003, 33, 4087. (i) Olszewski, T. K.; Boduszek,
B. Pol. J. Chem. 2005, 79, 553. (j) Olszewski, T. K.;
Boduszek, B.; Sobek, S.; Kozlowski, H. Tetrahedron 2006,
62, 2183. (k) Goldeman, W.; Olszewski, T. K.; Boduszek,
B.; Sawka-Dobrowolska, W. Tetrahedron 2006, 62, 4506.
(l) Guzik, M.; Olszewski, T. K.; Boduszek, B. Pol. J. Chem.
2007, 81, 1879. (m) Koroteev, A. M.; Bobrikova, A. A.;
Koroteev, M. P.; Lysenko, K. A.; Nifant’ev, E. E. Russ. J.
Gen. Chem. (Engl. Transl.) 2008, 78, 185; Chem. Abstr.
2008, 150, 191752. (n) Du, L.-Z.; Gong, J.-F.; Zhu, Y.; Wu,
Y.-J.; Song, M.-P. Inorg. Chem. Commun. 2006, 9, 529.
(o) Afarinkia, K.; Rees, C. W.; Cadogan, J. I. G. Tetrahedron
1990, 46, 7175. (p) Frolovskii, V. A.; Studnev, Yu. N.;
Rozantsev, G. G. Zh. Obshch. Khim. 1996, 66, 692; Chem.
Abstr. 1996, 125, 276015. It is worthy of note that N-
unsubstituted (1-aminoalkyl)diphenylphosphine oxides
could be obtained also in amidoalkylation reaction
Naturwissenschaften 1960, 47, 497. (e) Wieczorek, J. S.;
Gancarz, R. Rocz. Chem. 1976, 50, 2171. (f) Drauz, K.;
Koban, H. G.; Martens, J.; Schwarze, W. Liebigs Ann.
Chem. 1985, 448. (g) Lugovkin, B. P. Zh. Obshch. Khim.
1976, 46, 2498; Chem. Abstr. 1977, 86, 106726.
(h) Gartman, G. A.; Pak, V. D.; Kozlov, N. D. Zh. Obshch.
Khim. 1979, 49, 2375.
(21) (a) Rachoń, J.; Wasielewski, C. Z. Chem. 1973, 13, 254.
(b) Wasielewski, C.; Antczak, K.; Rachoń, J. Pol. J. Chem.
1978, 52, 1315. (c) Rachoń, J.; Wasielewski, C.
Tetrahedron Lett. 1978, 19, 1609. (d) Nifantev, E. E.; Zyk,
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1371; Chem. Abstr. 1975, 82, 73099.
(22) However, there is a note in the paper published by Sobanov
et al., that ‘the reaction between Schiff bases and dialkyl
hydrogen phosphonates thoroughly purified from traces of
acidic admixtures does not take place: Sobanov, A. A.;
Zolotukhin, A. V.; Galkina, I. V.; Galkin, V. I.; Cherkasov,
R. A. Russ. J. Gen. Chem. (Engl. Transl.) 2006, 76, 421;
Chem. Abstr. 2006, 146, 62804.
(q) Oleksyszyn, J. Synthesis 1981, 444. (r) Oleksyszyn, J.
J. Prakt. Chem. 1987, 329, 19.
(16) Tyka, R. Tetrahedron Lett. 1970, 11, 677.
Synthesis 2010, No. 14, 2437–2445 © Thieme Stuttgart · New York