1-Amino-1-aryl- and 1-amino-1-heteroaryl-methanephosphonic acids and their n-benzhydryl-protected diethyl esters: Preparation and characterization

Article abstract of DOI:10.1080/10426500490466274

N-Benzhydryl-protected diethyl esters of 1-amino-1-aryl- (phenyl, cumyl, p-dimethylaminophenyl, piperonyl, 1′-naphthyl, 9′-anthryl, 1′-pyrenyl) and 1-amino-1-heteroaryl- (furyl, 2′-thienyl, 3′-thienyl, 2′-pyrrolyl)-methanephosphonic acids, prepared by the

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1-AMINO-1-ARYL- AND 1-AMINO-1-HETEROARYL-
METHANEPHOSPHONIC ACIDS AND THEIR N-
BENZHYDRYL–PROTECTED DIETHYL ESTERS:
PREPARATION AND CHARACTERIZATION
Harry R. Hudson a , Rosalind J. Lee a & Ray W. Matthews a
a London Metropolitan University, London, United Kingdom
Version of record first published: 16 Aug 2010.
To cite this article: Harry R. Hudson , Rosalind J. Lee & Ray W. Matthews (2004): 1-AMINO-1-ARYL- AND 1-AMINO-1-
HETEROARYL-METHANEPHOSPHONIC ACIDS AND THEIR N-BENZHYDRYL–PROTECTED DIETHYL ESTERS: PREPARATION AND
CHARACTERIZATION, Phosphorus, Sulfur, and Silicon and the Related Elements, 179:9, 1691-1709
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Phosphorus, Sulfur, and Silicon, 179:1691–1709, 2004
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ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490466274
1-AMINO-1-ARYL- AND
1-AMINO-1-HETEROARYL-METHANEPHOSPHONIC
ACIDS AND THEIR N-BENZHYDRYL–PROTECTED
DIETHYL ESTERS: PREPARATION AND
CHARACTERIZATION
Harry R. Hudson, Rosalind J. Lee, and Ray W. Matthews
London Metropolitan University, London, United Kingdom
(Received December 30, 2003; accepted March 1, 2004)
N-Benzhydryl-protected diethyl esters of 1-amino-1-aryl- (phenyl,
cumyl, p-dimethylaminophenyl, piperonyl, 1ꢁ-naphthyl, 9ꢁ-anthryl,
1ꢁ-pyrenyl) and 1-amino-1-heteroaryl- (furyl, 2ꢁ-thienyl, 3ꢁ-thienyl,
2ꢁ-pyrrolyl)-methanephosphonic acids, prepared by the addition of di-
ethyl phosphite to the corresponding benzhydryl imines, have been iso-
lated, purified, and characterized. The presence of chiral α-carbon and
prochiral phosphorus in these esters gives rise to complicated features in
their NMR spectra, which are discussed. Hydrolysis of the crude 1-aryl
compounds in situ gave modest yields of the corresponding aminophos-
phonic acids (except for 1ꢁ-pyrenyl). Of the 1-heteroaryl derivatives,
only the 2ꢁ-thienyl compound gave the expected aminophosphonic acid;
in other cases, alternative modes of decomposition may occur under
hydrolytic conditions. NMR and mass spectral data are given for all
products.
Keywords: Aminophosphonate; aminophosphonic acids; aryl; het-
eroaryl; mass spectrometry; NMR
INTRODUCTION
Aminophosphonic acids and their derivatives have attracted
widespread interest in the agrochemical and biomedical fields.1 Among
the aralkyl types, derivatives of α-aminophenylmethanephosphonic
We thank the Higher Education Funding Council for England (HEFCE) for financial
support of a studentship (for R. J. Lee) and Prof. Dr. Gerhard Ha¨gele of the Heinrich-
Heine-Universita¨t, Du¨sseldorf, for helpful discussions. We are grateful to Mr. John
Crowder for assistance with nmr spectroscopy, Mr. Wimal Dissanayake for recording
the mass spectra, and Mr. S. Boyer for microanalysis.
Address correspondence to Harry R. Hudson, Emeritus Professor of Chemistry,
London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.
1691

1692
H. R. Hudson et al.
acid (5, R = Ph), the phosphonic analogue of α-phenylglycine, have been
shown to exhibit activity as herbicides and plant growth regulators,2
agrochemical fungicides,3,4 and glutamate receptor agonists and
antagonists in the pharmacological field.5 Also, a number of het-
eroaromatic analogues (5, R = furyl, thienyl, pyrrolyl, or pryidyl) have
attracted interest as potential herbicides and as structural units in
phosphonopeptides with enzyme inhibitory properties.6
A common method for the synthesis of aminophosphonates involves
the addition of dialkyl phosphite to an imine (3) giving, in the first
instance, an N-protected ester (4) of the corresponding amino acid
(Scheme 1).7 Addition is both acid- and base-catalyzed but may also
occur simply on heating. The use of an imine derived from a tertiary
benzylic amine (X = PhCR1R2),8 tritylamine (X = Ph3C),9or ben-
zhydrylamine (X = Ph2CH)10,11 has the advantage that N-deprotection
can be carried out by hydrolysis rather than hydrogenolysis, which is
necessary for the removal of N-benzyl groups (X = PhCH2).12 Thus, the
in situ hydrolysis of N-benzhydrylaminophosphonate esters (4, X =
Ph2CH) has been used by various workers10,11,13−17 in a convenient
“one-pot” procedure for the preparation of free aminophosphonic acids
(5).
SCHEME 1
In addition, the N-protected esters (4) may undergo selective
ester hydrolysis (via the use of trimethylsilyl bromide) to give
N-protected aminophosphonic acids,18,19 or selective N-deprotection,
by hydrogenolysis12 or by reaction with hydrogen bromide in acetic
acid9,20,21 to give aminophosphonic esters, which are important inter-
mediates in the synthesis of phophonopeptides.22

Aminophosphonic Acids
1693
DISCUSSION
We have previously used imines derived from benzhydrylamine in the
one-pot synthesis of fluorinated 1-amino-1-phenylmethanephosphonic
acids, and for the first time we isolated, purified, and characterized
the intermediate N-benzhydryl-protected esters.13 In continuation of
these studies, we now report the synthesis and characterization of a fur-
ther series of N-benzhydryl-protected 1-amino-1-aryl- and 1-amino-1-
heterocyclyl-methanephosphonates (8, Scheme 2). In addition we report
our investigations of the in situ hydrolysis of these esters as a method for
obtaining the corresponding aminophosphonic acids (9, Scheme 3), sev-
eral of which are novel compounds. None of the N-benzhydryl–protected
esters (8a–8k) has previously been isolated and characterized, although
two examples, the 1-phenyl (8a) and 1-(2ꢁ-thienyl) (8j) derivatives, were
obtained as intermediates that were hydrolyzed in situ during the
course of one-pot syntheses involving benzhydrylamine.10,15
SCHEME 2
In the present investigations imine intermediates (7a–7k) were
prepared (Scheme 2) by the interaction of equimolar quantities of
benzhydrylamine (or its hydrochloride) and the corresponding alde-
hyde (6a–6k) in the presence of an excess of anhydrous potassium
carbonate.8,23 Products were recrystallized from a mixture of toluene

1694
H. R. Hudson et al.
SCHEME 3
and light petroleum spirit before use in the next stage of the synthe-
sis. The diethyl phosphonate esters (8a–8k) were prepared by heating
equimolar mixtures of diethyl phosphite and the corresponding imine
in the absence of solvent, usually at temperatures between 90 and
100◦C. The use of a solvent is known to reduce the rate of addition.24
Reactions were monitored by 31P NMR until optimum conversion was
achieved, and the products (δP 21–26 ppm) were recrystallized from
ethyl acetate to give yields of 50–90%. A higher reaction temperature
(125–140◦C) was necessary in the synthesis of diethyl 1-(1ꢁ-pyrenyl)-1-
benzhydrylaminomethanephosphonate (8d) because of the high melt-
ing point of the imine, which failed to form a liquid reaction mixture
with diethyl phosphite at lower temperatures. In most cases, extended
reaction times of more than 6 h resulted in some decomposition of the
desired products and the appearance of a new signal (δP 4 ppm) in addi-
tion to that of the starting diethyl phosphite (δP 7 ppm). It is likely that
the initial addition reaction is reversible and that prolonged heating al-
lows for alternative reactions of the starting materials. The by-product
(δP 4 ppm) has not been identified unambiguously, but the chemical shift
suggests that it is monoethyl phosphite25,26 formed by monodealkyla-
tion of the dialkyl ester.

Aminophosphonic Acids
1695
The N-benzhydryl–protected diethyl phosphonate eters (8) are well-
defined crystalline solids which were characterized by elemental anal-
ysis, NMR, and mass spectrometry.
Preparation of the Free Aminophosphonic Acids
Free α-aminoarylmethanephosphonic acids have previously been ob-
tained by the hydrochloric acid-catalyzed hydrolysis of the correspond-
ing N-benzhydryl-protected dialkyl esters, prepared as described above,
but without isolation and purification of the latter (Scheme 1).10,11,13–17
However, certain types of aminophosphonic acid derivative, including a
number of N-benzhydryl types, have been found to undergo phosphorus-
carbon fission under the conditions of acid hydrolysis, a factor that
might account for the small or modest yields of final products that are
obtained in certain cases.27
In the present work, in situ hydrolysis using concentrated hydrochlo-
ric acid under reflux (Scheme 3) was found to be suitable for the
preparation of most of the α-aryl derivatives, including the α-naphthyl
(9b) and 9-anthryl (9c) compounds, but in the heterocyclic series only
the 2ꢁ-thienyl compound (9j) was obtainable by this procedure. 1-
Aminobenzylphosphonic acid (9a) has been prepared previously by this
method.10,14 No free aminophosphonic acids were isolable from the hy-
drolysis products of the 1ꢁ-pyrenyl, 2ꢁ-pyrrolyl, furyl, or 3ꢁ-thienyl esters
(8d, 8h, 8i, and 8k, respectively). Further work is necessary to estab-
lish the exact cause in the case of the 1ꢁ-pyrenyl and 3ꢁ-thienyl sys-
tems, although the failure to obtain free aminophosphonic acids from
the furyl and 2ꢁ-pyrrolyl derivatives may be due to the instability of the
furyl and pyrrolyl rings under acid conditions. Similar difficulties have
been reported elsewhere in attempts to prepare 1-amino-1-furyl- and
1-amino-1-(2ꢁ-pyrrolyl)-methanephosphonic acid by procedures that in-
volve acid hydrolysis.15,16 In addition, the possibility of phosphorus–
carbon fission, as reported for 2- and 4-pyridyl systems,17 and for 9-
fluorenyl–substituted aminophosphonates,27 might be a determining
factor. In these cases, alternative methods for deprotection and de-
esterification of the N-protected aminophosphonates are necessary if
the free aminophosphonic acids are required.15,16,28
Spectroscopic Characterization
NMR Spectroscopy
The diethyl phosphonate esters (8a–8k) exhibit 31P chemical shifts
in the range of 21–26 ppm. Chemicals shifts for the phenyl, substituted
phenyl, and polycyclic aromatic derivatives are all in the range of δP

1696
H. R. Hudson et al.
23–24 ppm. Only the 9-anthryl derivative resonates at slightly lower
field (δP 26 ppm). The highest field signal among the compounds under
investigation is shown by the furan derivative (δP 21 ppm), possibly
because of shielding by the ring oxygen atom.
1H and 13C NMR spectra of the diethyl phosphonate esters are
complicated by several structural factors. In addition to splitting due
to phosphorus coupling, the presence of a chiral carbon atom at-
tached to phosphorus causes the two ethoxy goups in each ester to
be anisochronous,29 as also are the two phenyl rings of the diphenyl-
methylamino moiety. In addition, the fact that the phosphorus atom
is prochiral results in the methylene protons within each ethyl group
being anisochronous,30 although in the examples given here chemical
shift nonequivalence is seen clearly for the protons of only one of the
two methylene groups. Thus, one of the CH2 groups gives rise to two
distinct and separate multiplets, whereas the other appears as only
one complex region of overlapping peaks (Table I). This difference in
behavior of the two methylene groups in any one diethyl ester may be
attributed to differences in orientation of the ethoxy groups with respect
to the 1-benzhydrylamino and 1-aryl substituents, and to the differing
influences of associated ring currents.31–35
The 13C spectra show, as expected, two methyl and two methylene
signals for each diethyl ester, all of which appear as doublets due to
phosphorus–carbon coupling (Table II).
TABLE I 1H NMR Parameters (δ/ppm, J/Hz) for the Ethoxy Group Protons of
Diethyl Phosphonate Esters (8a–8k)
Upfield
Downfield
CHA of
CHB of
Downfield
Compound
CH3
CH3
upfield CH2 upfield CH2
CH2
8a
1.07, 3JHH 7.06, 1.36, 3JHH 7.07,
3.62–3.78
3.83–3.99
4.12–4.29
4JPH 0.57
4JPH 0.56
8b
8c
8d
8e
0.76, 3JHH 7.06 1.36, 3JHH 7.06
0.62, 3JHH 7.10 1.35, 3JHH 7.12
0.75, 3JHH 7.05 1.38, 3JHH 7.04
1.12, 3JHH 7.03, 1.35, 3JHH 6.98,
3.34–3.43
3.27–3.37
3.35–3.45
3.76–3.90
3.70–3.79
3.61–3.71
3.67–3.80
3.93–4.14
4.14–4.35
4.12–4.31
4.18–4.39
4.19–4.23
4JPH 0.43
4JPH 0.43
8f
1.01, 3JHH 7.07 1.25, 3JHH 7.01
1.07, 3JHH 7.11 1.35, 3JHH 7.05
1.01, 3JHH 6.96 1.33, 3JHH 7.06
1.15, 3JHH 6.97 1.36, 3JHH 7.19
1.15, 3JHH 7.01 1.35, 3JHH 7.12
1.11, 3JHH 7.05, 1.36, 3JHH 7.05,
3.61–3.77
3.62–3.75
3.41–3.51
3.80–4.00
3.80–3.93
3.69–3.84
3.82–3.97
3.85–3.95
3.67–3.76
4.01–4.09
3.97–4.09
3.88–4.03
4.07–4.27
4.14–4.29
4.00–4.21
4.17–4.33
4.13–4.30
4.10–4.33
8g
8h
8i
8j
8k
4JPH 0.47
4JPH 0.46

Aminophosphonic Acids
1697
TABLE II 13C NMR Parameters (δ/ppm, J/Hz) for the Ethoxy Groups of
Diethyl Phosphonates (8a–8k)
Compound
Upfield CH3
Downfield CH3
Upfield CH2
Downfield CH2
8a
8b
8c
8d
8e
8f
8g
8h
8i
16.14, 3JPC 6.23 16.29, 3JPC 6.29 62.59, 2JPC 6.92 62.97, 2JPC 7.23
15.73, 3JPC 5.85 16.43, 3JPC 6.10 62.46, 2JPC 6.98 62.90, 2JPC 6.92
15.90, 3JPC 5.72 16.68, 3JPC 5.98 62.64, 2JPC 6.98 62.78, 2JPC 7.42
16.15, 3JPC 5.66 16.77, 3JPC 5.91 62.83, 2JPC 6.79 63.35, 2JPC 6.78
16.28, 3JPC 5.97 16.57, 3JPC 5.85 62.65, 2JPC 7.25 63.02, 2JPC 7.33
16.42, 3JPC 5.84 16.84, 3JPC 5.99 62.86, 2JPC 6.37 63.21, 2JPC 7.20
16.26, 3JPC 5.79 16.57, 3JPC 5.91 62.54, 2JPC 6.86 62.80, 2JPC 6.86
16.14, 3JPC 6.89 16.56, 3JPC 6.16 62.68, 2JPC 6.79 63.07, 2JPC 6.79
16.28, 3JPC 5.85 16.55, 3JPC 6.35 62.19, 2JPC 6.86 62.53, 2JPC 6.79
16.26, 3JPC 6.23 16.55, 3JPC 6.23 62.96, 2JPC 6.73 63.31, 2JPC 6.98
16.35, 3JPC 6.14 16.69, 3JPC 5.82 62.79, 2JPC 6.82 63.20, 2JPC 6.84
8j
8k
Apart from the complex overlapping peaks associated with the ethoxy
and aryl (or heteroaryl) goups, the NMR spectra of the esters exhibit
well-separated and characteristic signals for the two CH groups in each
molecule (Table III). For the methine proton of the benzhydryl group the
chemical shift is almost constant for all compounds (δH 4.41–4.86 ppm),
and is upfield from the corresponding signal of the parent imine (δH
5.43–5.91 ppm). In one example (8a) it is split by 4-bond coupling to
phosphorus (4JPH 1.13 Hz), although this is unusual. The proton of the
α-CH group (adjacent to phosphorus) shows more variation in chemical
TABLE III Proton and Carbon-13 NMR Parameters for the Methine Groups
(P CH NH CH) in Compounds 8a–8k
Compound
δ(P-CH)
2JPCH
δ(N-CH)
δ(P-C)
1JPC
δ(N-C)
3JPCNC
8a
8b
8c
8d
8e
8f
8g
8h
8i
3.93
4.86
5.62
5.41
3.84
3.91
3.83
3.94
4.04
4.21
4.05
22.47
23.31
26.78
22.80b
20.07
22.01
22.05
22.52
23.73
22.40
22.01
4.68a
4.65
4.41
4.61
4.70
4.71
4.72
4.81
4.74
4.86
4.74
57.99a
52.05a
53.84
52.95
57.69
57.75
57.22
51.53
52.02
53.45
53.74
155.3
155.0
157.3
158.4
156.7
155.6
157.4
161.8
163.0
130.5
157.9
63.56
63.76
64.53
64.09
63.56
63.89
63.35
63.87
64.47
63.79
64.05
17.04
16.67
15.41
16.98
16.86
17.05
17.23
17.17
16.29
15.79
16.35
8j
8k
aDoublet 4JPH 1.13.
bDoublet of doublets; the coupling of this proton to the NH proton (3JHH) was not
resolved well enough to measure.
cDoublet 4JPH 2.67.

1698
H. R. Hudson et al.
TABLE IV 1H, 13C and 31P NMR Parameters for Aminophosphonic Acids (9)
Compound
δ(P CH)
2JP-CH
δ(P C)
1JPC
δP
9b
9c
9e
9f
9g
9j
4.76
5.54
3.73
3.79
3.74
4.19
16.1
22.3
15.2
15.5
15.0
15.1
52.6
54.3
58.1
58.0
57.6
53.9
131.1
130.1
132.5
131.6
132.8
133.6
18.8
18.4
18.2
18.4
18.6
17.3
shift according to the substitutent group present, ranging from 3.83–
4.05 ppm for the heterocyclic (8h–8k) and phenyl (8a) or substituted
phenyl derivatives (8e–8g) but lying further downfield (4.86–5.62 ppm)
for the polycyclic aromatic compounds (8b–8d). All are at significantly
higher field than the signal for the corresponding imino proton of the
precursor (δH 8.13–9.49 ppm) and appear as characteristic doublets
(2JPH 20–27 Hz). In the 13C spectra, both methine carbon atoms are
split by phosphorus to give characteristic doublets in the region 51.53–
57.99 ppm (1JPC 130.5–163.0 Hz) for the carbon atom attached to phos-
phorus and 63.35–64.53 ppm (1JPC 15.41–17.23 Hz) for the methine
carbon of the benzhydryl group.
Because of the low aqueous solubility of the free amino acids (9b,
9c, 9e–9g, and 9j), their NMR spectra were recorded in NaOD solu-
tion in D2O. Under these conditions the 31P chemical shift, which is
pH-dependent, is in the range 17–19 ppm. The 1H and 13C NMR spec-
tra are relatively simple, showing the expected aromatic region for the
α-substituent in each case, and simple doublets for the carbon and hy-
drogen of the α-CH group (Table IV).
Mass Spectrometry
Electron impact mass spectral data are shown in Table V for the N-
protected diethyl esters and LSIMS data are given for the aminophos-
phonic acids in Table VI. Molecular (or pseudomolecular) ions, although
variable in intensity, were observed in all cases. Fragmentation of the
esters involves either C-N fission, to give the stable benzhydryl cation
(m/z 167), usually as the base peak, or P-C fission, with or without
hydrogen transfer, and the consequent loss of diethyl phosphite or the
diethoxyphosphonyl radical. As noted previously in other cases,13,36,37
LSIMS spectra of the aminophosphonic acids are relatively simple; the
major fragmentation occurs by loss of phosphorous acid from the proto-
nated molecular ion, and in several cases the loss of a hydroxyl group
is observed.

Aminophosphonic Acids
1699
TABLE V Principal Fragments (m/z, %) in the EI Mass Spectra of Diethyl
Phosphonate Esters (8a–8k)
Compound
M+.
[M–(EtO)2PO]+
[M – (EtO)2PHO]+.
Ph2CH+(m/z 167)
8a
8b
8c
8d
8e
8f
8g
8h
8i
409, (10)
459, (1)
509, (38)
534, (3)
453, (4)
451, (7)
452, (3)
398, (20)
399, (8)
415, (4)
415, (3)
272, (62)
322, (22)
372, (67)
397, (13)
316, (0)
314, (56)
314, (33)
261, (81)
263, (0)
271, (47)
321, (8)
(100)
(100)
(100)
(100)
(100)
(100)
(67)a
(100)
(100)
(100)
(100)
371, (55)
396, (55)
315, (74)
313, (74)
313, (13)
260, (21)
262, (44)
277, (48)
277, (57)
8j
8k
278, (65)
278, (10)
aBase peak m/z 65.
EXPERIMENTAL
Materials and Instrumentation
Starting materials, solvents, and reagents were obtained commercially
and were mainly used as supplied. Diethyl ether was dried over sodium
1
wire. H NMR spectra were obtained on a Bruker AM250 spectrom-
eter operating at 250.133 MHz. 13C NMR spectra (broad-band pro-
ton decoupled, DEPT-135 and DEPT-90) were obtained on a Bruker
AM250 spectrometer operating at 62.896 MHz. Samples were dissolved
in CDCl3 containing tetramethylsilane (TMS) as the internal refer-
ence, or in NaOD/D2O containing sodium 3-trimethylsilylpropionate-d4
1
(Me3SiCD2CD2CO2Na; TSP) as the internal reference. 31P{ H} NMR
spectra were recorded on Bruker AM250 and WP80-SY instruments
operating at 101.256 MHz and 32.44 MHz, respectively. Samples were
TABLE VI Principal Ions (m/z, %) in the LSIMS of Aminophosphonic Acids
(9)a
Compound
[MH − (H3PO3)]+
[MH − (OH)]+
[(MH)]+
[MH + (G)]+
9b
9cb
9e
9f
9g
9j
—
221 (15)
271 (26)
215 (17)
—
214 (96)
—
238 (100)
288 (11)
232 (6)
230 (18)
231 (12)
194 (100)
—
—
324 (2)
322 (4)
323 (2)
286 (72)
206 (34)
150 (100)
148 (100)
149 (100)
—
aG represents a molecule of glycerol matrix.
bBase peak m/z 149.

1700
H. R. Hudson et al.
dissolved in CDCl3 or NaOD/D2O, with H3PO4 as the external reference.
Microanalysis for carbon, hydrogen, nitrogen, and sulfur was carried
out on a Carlo Erba 1106 elemental analyzer. Low-resolution electron
impact mass spectra were obtained using a Kratos Profile HV3 spec-
trometer with an ionizing energy of 70 eV. LSIMS data were obtained
on the same instrument using a glycerol matrix and with a primary
beam of caesium ions generated in an ion gun operating at 10 kV. Melt-
ing points were recorded on an electrothermal digital melting point
apparatus and are uncorrected.
Preparations of Imines (7): General Procedure
Equimolar quantities (0.03–0.1 mol) of benzhydrylamine and the aro-
matic aldehyde (6a–6d) or of benzhydrylamine hydrochloride and the
aldehyde (6e–6k) were dissolved in dichloromethane or anhydrous
ether to give a solution (15–40% w/v) which was stirred for 6 h at room
temperature in the presence of an excess of anhydrous potassium car-
bonate. The solution was filtered, the solvent was removed under re-
duced pressure, and the residue was recrystallized from toluene and
petroleum spirit (b.p. 40–60◦C), to give the following products.
N-Benzylidene-1,1-diphenylmethylamine14 (7a) (4.89 g, 66.7%), as a
white crystalline solid, m.p. 104–105◦C (Calculated for C20H17N: C,
88.5; H, 6.3; N, 5.2%. Found: C, 88.5; H, 6.4; N, 5.2). δH (CDCl3) 5.59 (1H,
s, Ph2CH), 7.17–7.42 (13H, m, Ar), 7.81–7.85 (2H, m, Ar), 8.40 (1H, s,
N CH); δC (CDCl3) 77.77 (Ph2C), 126.88, 127.58, 128.34, 128.40, 130.63,
136.18, 143.83 (Ar), 160.63 (N C); EI ms: m/z 271 (M+, 66.7%).
N-(1ꢁ-Naphthylmethylidene)-1,1-diphenylmethylamine (7b) (29.71 g,
92.2%), as a yellow crystalline solid, m.p. 109–110◦C (C24H19N requires:
C, 89.7; H, 6.0; N, 4.4%. Found: C, 89.8; H, 6.0; N, 4.3). δH (CDCl3)
5.59 (1H, s, Ph2CH), 7.12–7.52 (14H, m, Ar), 7.71–7.75 (2H, m, Ar),
8.92 (1H, s, N CH), 9.09 (1H, m, Ar); δC (CDCl3) 79.23 (Ph2C), 124.66,
125.05, 125.93, 126.92, 127.14, 127.61, 128.43, 128.48, 129.78, 131.14,
131.28, 131.37, 133.72, 143.97 (Ar), 160.85 (s, N C); EI ms: m/z 321
(M+, 21.8%).
N-(9ꢁ-Anthrylmethylidene)-1,1-diphenylmethylamine (7c) (6.45 g,
87.0%), as a yellow crystalline solid, m.p. 139◦C (C28H21Nrequires: C,
90.5; H, 5.7; N, 3.8%. Found: C, 90.3; H, 5.6; N, 3.7). δH (CDCl3) 5.83
(1H, s, Ph2CH), 7.20–7.41 (10H, m, Ar), 7.50–7.53 (4H, m, Ar), 7.86–7.90
(2H, m, Ar), 8.33 (1H, s, Ar) 8.37–8.43 (2H, m, Ar), 9.49 (1H, s, N CH);
δC (CDCl3) 80.29 (Ph2C), 125.01, 125.35, 126.82, 127.32, 127.94, 128.80,
128.98, 129.69, 130.29, 131.39, 143.94 (Ar), 160.70 (N C); EI ms: m/z
371 (M+, 22.8%).

Aminophosphonic Acids
1701
N-(1ꢁ-Pyrenylmethylidene)-1,1-diphenylmethylamine (7d) (26.85 g,
67.9%), as a yellow crystalline solid, m.p. 180–181◦C (C28H21N requires:
C, 91.1; H, 5.4; N, 3.5%. Found: C, 90.9; H, 5.6; N, 3.4). δH (CDCl3) 5.80
(1H, Ph2CH), 7.23–7.57 (10H, m, Ar), 7.98–8.18 (5H, m, Ar), 8.14 (1H,
d, 3JHH 8.07, Ar), 8.20 (1H, d, 3JHH 9.21, Ar) 8.65 (1H, d, Ar), 9.01 (1H,
d, Ar), 9.42 (1H, s, N CH); δC (CDCl3) 79.27 (s, Ph2C), 122.84, 124.84,
125.64, 125.87, 126.08, 127.10, 127.04, 127.43, 127.74, 128.70, 124.59,
130.02, 130.57, 131.22, 132.91, 144.14 (Ar), 159.84 (s, N C); EI ms: m/z
395 (M+, 2.0%).
N-Piperonylidene-1,1-diphenylmethylamine (7e) (16.73 g, 53.1%), as
a white crystalline solid, m.p. 115–116◦C (C21H17NO2 requires: C, 80.0;
H, 5.4; N, 4.4%. Found: C, 80.1; H, 5.4; N, 4.4). δH (CDCl3) 5.55 (1H,
s, Ph2CH), 5.97 (2H, s, OCH2O), 6.80 (1H, d, Ar), 7.14 (1H, dd, Ar),
7.18–7.40 (10H, m, Ar) 7.52 (1H, d, Ar), 8.29 (1H, s, N CH); δC (CDCl3)
77.63 (s, Ph2C), 101.41, 106.92, 107.96, 124.73, 126.93, 127.65, 128.41,
131.27, 144.07 (Ar), 148.22 (Ar-O), 149.94 (Ar-O), 159.83 (s, N C); EI
ms: m/z 315 (M+, 30.0%).
N-(4ꢁ-Isopropylbenzylidene)-1,1-diphenylmethylamine43 (7f) (16.54
g, 52.8%), as a white crystalline solid, m.p. 63–64◦C (Calculated
for C23H23N: C, 88.1; H, 7.4; N, 4.5%. Found: C, 88.2; H, 7.5; N, 4.4). δH
(CDCl3) 1.21 (6H, d, 3JHH 6.81, 2 × CH3), 2.87 (1H, septet, CHCH3), 5.55
(1H, Ph2CH), 7.13–7.76 (14H, m, Ar), 8.34 (1H, s, N CH); δC (CDCl3)
23.79 (2 × CH3), 34.08 (CHCH3), 77.79 (s, Ph2C), 123.58, 126.86, 127.67,
128.34, 128.52, 134.13, 143.99, 151.86 (Ar), 160.59 (N C); EI ms: m/z
313 (M+, 48.8%).
N-(4ꢁ-Dimethylaminobenzylidene)-1,1-diphenylmethylamine
(7g)
(28.98 g, 92.3%), as an orange crystalline solid, m.p. 140–141◦C
(Calculated for C22H22N2: C, 84.0; H, 7.0; N, 8.9%. Found: C, 84.0; H,
7.1; N, 8.9). δH (CDCl3) 2.92 (6H, s, 2 × CH3), 5.51 (1H, s, Ph2CH),
6.64 (2H, d, Ar), 7.13–7.40 (10H, m, Ar), 7.69 (2H, d, Ar), 8.82 (1H,
s, N CH); δC (CDCl3) 40.12 (2 × CH3), 77.69 (Ph2C), 111.49, 124.61,
126.68, 127.74, 128.26, 129.79, 144.47, 152.07 (Ar), 160.56 (N C); EI
ms: m/z 314 (M+, 20.7%).
N-(2ꢁ-Pyrrolylmethylidene)-1,1-diphenylmethylamine (7h) (8.30 g,
55.3%), as a yellow crystalline solid, m.p. 160–162◦C (C18H16N requires:
C, 83.0; H, 6.2; N, 10.8%. Found: C, 82.9; H, 6.3; N, 10.9). δH (CDCl3)
5.56 (1H, Ph2CH), 6.22 (1H, dd, 3JH3−H4 3.65 and 3JH4−H5 2.56, pyrrolyl
4
4-H), 6.51 (1H, dd, JH3−H5 1.10, pyrrolyl 3-H), 6.84 (1H, dd, pyrrolyl
5-H), 7.18–7.35 (10H, m, Ar), 8.13 (1H, s, N CH); δC (CDCl3) 77.66
(Ph2C), 110.16 (pyrrolyl 4-C), 115.54 (pyrrolyl 3-C), 122.68 (pyrrolyl 5-
C), 127.10, 127.82, 128.47, 129.76 (Ar), 143.37 (pyrrolyl 2-C), 151.34
(N C); EI ms: m/z 260 (M+, 21.7%).

1702
H. R. Hudson et al.
N-Furfurylidene-1,1-diphenylmethylamine (7i) (21.0 g, 80.4%), as
a pale yellow crystalline solid; m.p. 110–112◦C (C18H15NO requires:
C, 82.7; H, 5.8; N, 5.4%. Found: C, 82.8; H, 5.8; N, 5.4). δH (CDCl3) 5.53
3
3
(1H, s, Ph2CH), 6.36 (1H, dd, JH4−H3 3.42 and JH4−H5 1.75, furyl 4-
H), 6.72 (1H, dd, 4JH3−H5 0.67, furyl 3-H), 7.17–7.37 (10H, m, Ar), 7.44
(CH, dd, furyl 5-H), 8.13 (1H, s, N CH); δC (CDCl3) 77.92 (Ph2C), 111.61
(furyl 4-C), 114.5 (furyl 3-C), 126.99, 127.73, 128.38, 143.27 (Ar), 144.79
(furyl 5-C), 149.63 (N C), 151.54 (furyl 2-C); EI ms: m/z 261 (M+, 61.9).
N-(2ꢁ-Thienylmethylidene)-1,1-diphenylmethylamine (7j) (4.30 g,
35.3%); m.p. 95◦C (C18H15NS requires: C, 77.9; H, 5.4; N, 5.0; S, 11.6%.
Found: C, 77.9; H, 5.4; N, 5.0; S, 11.7). δH (CDCl3) 5.57 (1H, s, Ph2CH),
2
2
7.01 (1H, dd, JH3−H4 5.00 and JH4−H5 3.62, thienyl 4-H), 7.17–7.38
(12H, m, Ar overlapping with thienyl 3-H and 5-H), 8.43 (1H, s, N CH);
δC (CDCl3) 77.21 (Ph2C), 127.09 (Ar), 127.41 (thienyl 4-C), 127.82,
128.54 (Ar), 129.25 (thienyl 3-C), 130.77 (thienyl 5-C), 142.85 (thienyl
2-C), 143.76 (Ar), 154.12 (N C); EI ms: m/z 277 (M+, 80.7%).
N-(3ꢁ-Thienylmethylidene)-1,1-diphenylmethylamine (7k) (6.0 g,
49.6%); m.p. 80–81◦C (C18H15NS requires: C, 77.9; H, 5.4; N, 5.0; S,
11.6%. Found: C, 77.9; H, 5.4; N, 5.0; S, 11.7). δH (CDCl3) 5.52 (1H,
s, Ph2CH), 7.14–7.38 (11H, m, Ar overlapping with thienyl 5-H), 7.55
(1H, dd, thienyl 4-H), 7.63 (1H, dd, thienyl 2-H), 8.35 (1H, s, N CH); δC
(CDCl3) 77.63 (Ph2C), 125.95 (thienyl 5-C), 126.10 (thienyl 4-C), 126.85,
127.58, 128.31 (Ar), 128.63 (thienyl 2-C), 140.51 (Ar), 143.70 (thienyl
3-C), 154.98 (N C); EI ms: m/z 277 (M+, 23.0%).
Preparations of Diethyl Phosphonate Esters (8):
General Procedure
An equimolar mixture (0.003–0.07 mol) of diethyl phosphite and imine
(7) was heated (100◦C, except for 7d, for which a temperature of 140◦C
was necessary). Reactions were monitored by 31P NMR until optimum
conversion had been achieved: 4 h (7a, 7d), 5 h (7f), 6h (7e, 7g, 7h, 7i,
7j), 8 h (8c, 8k), and 10 h (8b). The oily product was triturated with
ethyl acetate and the precipitate, which formed was washed with the
minimum of diethyl ether and recrystallized from ethyl acetate to give
the following products.
Diethyl 1-phenyl-1-(diphenylmethylamino)methanephosphonate (8a)
(3.52 g, 71.6%), as a white crystalline solid, m.p. 98–99◦C (C24H28NO3P
requires: C, 70.4; H, 6.9; N, 3.3%. Found: C, 70.4; H, 6.9; N, 3.3). δH
(CDCl3) 1.07 (3H, d of t, 3JHH 7.06 and 4JPH 0.57, CH3), 1.36 (3H, d of t,
4
3JHH 7.07 and JPH 0.56, CH3), 2.56 (1H, br s, NH), 3.62–3.78 (1H, m,
2
HA of CH2), 3.83–3.99 (1H, m, HB of CH2), 3.93 (1H, d, JPH 22.47,
4
P CH), 4.12–4.29 (2H, m, CH2), 4.68 (1H, d, JPH 1.13, Ph2CH),

Aminophosphonic Acids
1703
3
7.14–7.40 (15H, m, Ar); δC (CDCl3) 16.14 (d, JPC 6.23, CH3), 16.29 (d,
1
2
3JPC 6.29, CH3), 57.99 (d, JPC 155.29, P-C), 62.59 (d, JPC 6.92, CH2),
2
3
62.97 (d, JPC 7.23, CH2), 63.65 (d, JPC 17.04, Ph2C), 127.11, 127.29,
127.92, 128.38, 128.56, 128.50, 128.66 (Ar), 135.89 (d, JPC 1.57), 142.00,
143.66 (Ar); δP (CDCl3) 23.70; EI ms: m/z 409 (M+, 9.7%).
Diethyl 1-(1ꢁ-naphthyl)-1-(diphenylmethylamino)methanephosphon-
ate (8b) (18.12 g, 53.3%), as a white crystalline solid, m.p. 102–103◦C
(C28H30NO3P requires: C, 73.2; H, 6.6; N, 3.0%. Found: C, 73.3; H, 6.7;
N, 3.0). δH (CDCl3) 0.76 (3H, t, 3JHH 7.06, CH3), 1.36 (3H, t, 3JHH 7.06,
CH3), 2.74 (1H, br s, NH), 3.34–3.43 (1H, m, HA of CH2), 3.70–3.79
(1H, m, HB of CH2), 4.14–4.35 (2H, m, CH2), 4.65 (1H, s, Ph2CH), 4.86
(1H, br d, 2JPH 23.01, P-CH), 7.13–7.87 (17H, m, Ar); δC (CDCl3) 15.73
3
3
1
(d, JPC 5.85, CH3), 16.43 (d, JPC 6.10, CH3), 52.05 (d, JPC 155.03,
2
2
P-C), 62.46 (d, JPC 6.98, CH2), 62.90 (d, JPC 6.92, CH2), 63.76 (d,
3JPC 16.67, Ph2C), 122.99, 125.36 (d, JPC 3.33), 125.46, 125.77, 128.28,
126.48, 127.19, 127.03, 127.84, 128.25, 128.36, 128.53, 128.55, 132.14,
132.24, 133.55, 142.09, 143.50 (Ar); δP (CDCl3) 23.90; EI ms: m/z 459
(M+, 1.4%).
Diethyl 1-(9ꢁ-anthryl)-1-(diphenylmethylamino)methanephosphonate
(8c) (21.14 g, 51.9%), as a white crystalline solid, m.p. 122–123◦C
(C32H32NO3P requires: C, 75.4; H, 6.3; N, 2.7%. Found: C, 75.3; H, 6.1;
N, 2.6). δH (CDCl3) 0.62 (3H, t, 3JHH 7.10, CH3), 1.35 (3H, t, 3JHH 7.12,
CH3), 3.04 (1H, br s, NH), 3.27–3.37 (1H, m, HA of CH2), 3.61–3.71
(1H, m, HB of CH2), 4.12–4.31 (2H, m, CH2), 4.41 (1H, s, Ph2CH), 5.62
2
(1H, d, JPH 26.78, P-CH), 7.00–7.57 (15H, m, Ar), 7.93–7.98 (2H, 2 ×
3
3
d, Ar), 8.39 (1H, d, JHH 2.45, anthryl 13-H), 9.33 (1H, d, JHH 9.02,
anthryl 3-H); δC (CDCl3) 15.90 (d, 3JPC 5.72, CH3), 16.68 (d, 3JPC 5.98,
1
2
CH3), 53.84 (d, JPC 157.24, P-C), 62.64 (d, JPC 6.98, CH2), 62.78 (d,
2JPC 7.42, CH2), 64.53 (d, JPC 15.41, Ph2C), 123.47, 124.80, 125.36,
3
125.99, 126.13, 127.05 (d), 127.09, 127.48, 127.52, 128.30, 128.26,
128.62, 128.97 (d, JPC 4.09), 129.36, 130.90 (d, JPC 4.09), 131.35 (d,
JPC 1.95), 131.68, 131.83, 131.95 (d, JPC 3.40), 142.09, 143.39 (Ar); δP
(CDCl3) 25.60; EI ms: m/z 509 (M+, 37.9%).
Diethyl 1-(1ꢁ-pyrenyl)-1-(diphenylmethylamino)methanephosphonate
(8d) (0.93 g, 69.7%), as a white crystalline solid, m.p. 107–108◦C
(C34H32NO3P requires: C, 76.5; H, 6.0; N, 2.6%. Found: C, 76.5; H, 6.1;
N, 2.5). δH (CDCl3) 0.75 (3H, t, 3JHH 7.05, CH3), 1.38 (3H, t, 3JHH 7.04,
CH3), 3.02 (1H, br s, NH), 3.35–3.45 (1H, m, HA of CH2), 3.67–3.80
(1H, m, HB of CH2), 4.18–4.39 (2H, m, CH2), 4.61 (1H, s, Ph2CH), 5.41
2
(1H, br dd, JPH 22.80, P-CH), 7.10–7.33 (10H, Ar), 7.76–8.45 (9H,
3
3
Ar); δC (CDCl3) 16.15 (d, JPC 5.66, CH3), 16.77 (d, JPC 5.91, CH3),
52.95 (br d, 1JPC 158.37, P-C), 62.83 (d, 2JPC 6.79, CH2), 63.35 (d, 2JPC
6.98, CH2), 64.09 (d, 3JPC 16.98, Ph2C), 122.65, 124.86, 124.95, 125.15,

1704
H. R. Hudson et al.
125.42, 125.62, 126.12, 127.28, 127.55, 127.63, 127.70, 127.34, 128.23,
128.55, 128.74, 130.02, 130.80, 130.17 (d, JPC 7.67), 131.02 (d, JPC
2.70), 131.48, 142.26, 143.75 (Ar); δP (CDCl3) 23.74; EI ms: m/z 534
(M+, 3.0%).
Diethyl 1-(piperonyl)-1-(diphenylmethylamino)methanephosphonate
(8e) (18.9 g, 93.0%), as a white crystalline solid, m.p. 119–120◦C
(C25H28NO5P requires: C, 66.2; H, 6.2; N, 3.1%. Found: C, 66.4; H, 6.4;
N, 3.0). δH (CDCl3) 1.12 (3H, d of t, 3JHH 7.03 and 4JPH 0.43, CH3), 1.35
(3H, d of t, 3JHH 6.98 and 4JPH 0.43, CH3), 2.52 (1H, br s, NH), 3.76–3.90
2
(1H, m, HA of CH2), 3.84 (1H, d, JPC 20.07, P-CH) 3.93–4.14 (1H, m,
HB of CH2), 4.19–4.23 (2H, m, CH2), 4.70 (1H, s, Ph2CH), 5.93 (2H, s,
OCH2O), 6.74–6.80 (2H, Ar), 6.90 (1H, Ar), 7.15–7.35 (10H, m, 2 × Ph);
δC (CDCl3) 16.28 (d, 3JPC 5.79, CH3), 16.57 (d, 3JPC 5.85, CH3), 57.69 (d,
2
2
1JPC 156.70, P-C), 62.65 (d, JPC 7.25, ester CH2), 63.02 (d, JPC 7.33,
3
ester CH2), 63.56 (d, JPC 16.86, Ph2C), 101.92 (s, OCH2O), 108.22 (d,
JPC 1.76), 108.71 (d, JPC 5.41), 122.23, 122.35, 127.15, 127.25, 127.34,
127.85, 128.51 (d, JPC 12.39), 129.68, 142.01, 143.69 (Ar), 147.96 (Ar-O),
147.99 (Ar-O); δP (CDCl3) 23.67; EI ms: m/z 453 (M+, 4.5%).
Diethyl
1-(4ꢁ-isopropylphenyl)-1-(diphenylmethylamino)methane-
phosphonate (8f) (14.6 g, 62.4%), as a white crystalline solid, m.p.
88–90◦C (C27H34NO3P requires: C, 71.8; H, 7.6; N, 3.1%. Found: C,
3
71.9; H, 7.6; N, 3.1). δH (CDCl3) 1.01 (3H, t, JHH 7.07, CH3CH2), 1.25
3
3
[6H, d, JHH 7.01 (CH3)2CH], 1.33 (3H, t, JHH 7.05, CH3CH2), 2.59
(1H, br s, NH), 2.89 [1H, septet, CH(CH3)2], 3.61–3.77 (1H, m, HA of
CH2), 3.82–3.97 (1H, m, HB of CH2), 3.91 (1H, d, JPH 22.01, P-CH),
2
4.07–4.27 (2H, m, CH2), 4.71 (1H, s, Ph2CH), 7.10–7.37 (14H, m, Ar);
3
3
δC (CDCl3) 16.42 (d, JPC 5.84, CH3), 16.84 (d, JPC 5.99, CH3), 24.0
1
(s, CH3CH), 33.62 (s, CH3CH), 57.75 (d, JPC 155.6, P-C), 62.86 (d,
2JPC 6.37, CH2), 63.21 (d, 2JPC 7.20, CH2), 63.89 (d, 3JPC 17.05, Ph2C),
126.87 (d, JPC 2.14), 127.37, 127.56, 128.18, 128.66, 128.76, 128.83,
128.86, 133.33, 142.47, 144.10, 148.82 (d, JPC 3.14) (Ar); δP (CDCl3)
24.63; EI ms: m/z 451 (M+, 7.0%).
Diethyl 1-(4ꢁ-dimethylaminophenyl)-1-(diphenylmethylamino)metha-
nephosphonate (8g) (12.09 g, 87.6%), as a red-orange crystalline solid,
m.p. 108–109◦C (C26H33N2O3P requires: C, 69.1; H, 7.4; N, 6.2%.
3
Found: C, 69.3; H, 7.3; N, 6.3). δH (CDCl3) 1.07 (3H, t, JHH 7.11,
3
CH3CH2), 1.35 (3H, t, JHH 7.05, CH3CH2), 2.92 [6H, s, N(CH3)2],
3.62–3.75 (1H, m, HA of CH2), 3.85–3.95 (1H, m, HB of CH2), 3.83 (1H,
2
d, JPH 22.05, P-CH), 4.14–4.29 (2H, m, CH2), 4.72 (1H, s, Ph2CH),
6.70 (2H, d, Ar), 7.13–7.38 (13H, m, Ar); δC (CDCl3), 16.26 (d, 3JPC 5.79,
3
CH3CH2), 16.57 (d, JPC 5.91, CH3CH2), 40.40 [N(CH3)2], 57.22 (d,
1JPC 157.36, P-C), 62.54 (d, JPC 6.86, CH2), 62.80 (d, JPC 6.86, CH2),
2
2
3
63.35 (d, JPC 17.23, Ph2C), 112.37, 122.86, 126.99, 127.16, 127.27,

Aminophosphonic Acids
1705
127.88, 128.32, 128.48, 129.38 (d, JPC 6.54), 142.25, 143.98, 150.17 (d,
JPC 1.87) (Ar); δP (CDCl3) 25.12; EI ms: m/z 452 (M+, 3.0%).
Diethyl 1-(2ꢁ-pyrrolyl)-1-(diphenylmethylamino)methanephosphonate
(8h) (1.88 g, 59.2%), as a pale yellow crystalline solid, m.p. 88–90◦C
(C22H27N2O3P requires: C, 66.3; H, 6.8; N, 7.0%. Found: C, 66.3; H, 6.8;
N, 7.0). δH (CDCl3) 1.01 (3H, t, 3JHH 6.96, CH3), 1.33 (3H, t, 3JHH 7.06,
CH3), 2.67 (1H, br s, NH), 3.41–3.51 (1H, m, HA of CH2), 3.67–3.76 (1H,
m, HB of CH2), 3.94 (1H, d, 2JPH 22.52, P-CH), 4.00–4.21 (2H, m, CH2),
4.81 (1H, s, Ph2CH), 6.01 (1H, m, pyrrolyl 4-H), 6.13 (1H, m, pyrrolyl
3-H), 6.76 (1H, m, pyrrolyl 5-H), 7.13–7.41 (10H, m, Ar), 9.78 (1H, br s,
pyrrolyl NH); δC (CDCl3) 16.14 (d, 3JPC 6.89, CH3), 16.56 (d, 3JPC 6.16,
1
2
CH3), 51.53 (d, JPC 161.83, P-C), 62.68 (d, JPC 6.79, CH2), 63.07 (d,
2JPC 6.79, CH2), 63.87 (d, JPC 17.17, Ph2C), 107.68 (s, pyrrolyl 4-C),
109.52 (d, JCP 9.56, pyrrolyl 3-C), 118.62 (s, pyrrolyl 5-C), 125.27 (d,
3
4
2JCP 3.40, pyrrolyl 2-C), 126.88, 127.16, 127.29, 127.90, 128.24, 128.48,
142.56, 144.16 (Ar); δP (CDCl3) 23.96; EI ms: m/z 398 (M+, 19.8%).
Diethyl 1-furyl-1-(diphenylmethylamino)methanephosphonate (8i)
(10.64 g, 87%), as a white crystalline solid, m.p. 82–84◦C (C22H26NO4P
requires: C, 66.2; H, 6.6; N, 3.5%. Found: C, 66.4; H, 6.6; N, 3.5). δH
(CDCl3) 1.15 (3H, t, 3JHH 6.97, CH3), 1.36 (3H, t, 3JHH 7.19, CH3), 2.53
(1H, br s, NH), 3.80–4.00 (1H, m, HA of CH2), 4.01–4.09 (1H, m, HB
2
of CH2), 4.04 (1H, d, JPH 23.79, P-CH), 4.17–4.33 (2H, m, CH2), 4.74
(1H, s, Ph2CH), 6.29 (1H, m, furyl 4-H), 6.38 (1H, m, furyl 3-H), 7.15–
3
7.44 (11H, m, Ar and furyl 5-H); δC (CDCl3) 16.28 (d, JPC 5.85, CH3),
16.55 (d, 3JPC 6.35, CH3), 52.02 (d, 1JPC 163.0, P-C), 62.19 (d,2JPC 6.86,
CH2), 62.53 (d, 2JPC 6.79, CH2), 64.42 (d, 3JPC 16.29, Ph2C), 109.48 (d,
3JPC 7.86, furyl 3-C), 110.54 (s, furyl 4-C), 127.22 (s, furyl 5-C), 127.38,
127.77, 128.46, 128.58, 142.38, 142.68, 141.89, 143.59 (Ar), 149.88 (d,
2JPC 2.70, furyl 2-C); δP (CDCl3) 21.00; EI ms: m/z 399 (M+, 8.4%).
Diethyl 1-(2ꢁ-thienyl)-1-(diphenylmethylamino)methanephosphonate
(8j) (1.96 g, 87.5%), as a pale yellow crystalline solid, m.p. 93–95◦C
(C22H26NO3PS requires: C, 63.6; H, 6.3; N, 3.4; S, 7.7%. Found: C, 63.7;
H, 6.2; N, 3.4; S, 7.6). δH (CDCl3) 1.15 (3H, t, 3JHH 7.01, CH3), 1.35 (3H,
3
t, JHH 7.17, CH3), 2.76 (1H, br s, NH), 3.80–3.93 (1H, m, HA of CH2),
3.97–4.09 (1H, m, HB of CH2), 4.21 (1H, d, 2JPH 22.40, P-CH), 4.13–4.30
(2H, m, CH2), 4.86 (1H, s, Ph2CH), 6.98–7.02 (2H, m, thienyl 3-H and
4-H), 7.02–7.41 (11H, m, Ar and thienyl 5-H); δC (CDCl3), 16.26 (d, 3JPC
6.23, CH3), 16.55 (d, 3JPC 6.23, CH3), 53.45 (d, 1JPC 130.51, P-C), 62.96
(d, 2JPC 6.73, CH2), 63.31 (d, 2JPC 6.98, CH2), 63.79 (d, 3JPC 15.79, Ph2C),
3
125.51 (d, JPC 3.21, thienyl 3-C), 126.96, 127.21 (Ar), 127.08 (thienyl
4-C), 127.43 (thienyl 5-C), 127.88, 128.65, 128.43, 128.85 (Ar), 139.64
(thienyl 2-C), 141.80, 143.45 (Ar); δP (CDCl3) 21.93; EI ms: m/z 415 (M+,
4.5%).

1706
H. R. Hudson et al.
Diethyl 1-(3ꢁ-thienyl)-1-(diphenylmethylamino)methanephosphonate
(8k) (5.77 g, 50.2%), as a cream crystalline solid, m.p. 90–92◦C
(C22H26NO3PS requires: C, 63.6; H, 6.3; N, 3.4; S, 7.7%. Found: C, 63.7;
3
4
H, 6.3; N, 3.4; S, 7.6). δH (CDCl3) 1.11 (3H, d of t, JHH 7.05 and JPH
0.47, CH3), 1.36 (3H, d of t, 3JHH 7.05 and 4JPH 0.46, CH3), 2.33 (1H, br s,
NH), 3.69–3.84 (1H, m, HA of CH2), 3.88–4.03 (1H, m, HB of CH2), 4.05
(1H, d, 2JPH 22.01, P-CH), 4.10–4.33 (2H, m, CH2), 4.74 (1H, s, Ph2CH),
7.07–7.40 (13H, m, Ar and thienyl 2-H, 4-H and 5-H); δC (CDCl3), 16.35
(d, 3JPC 6.14, CH3), 16.69 (d, 3JPC 5.82, CH3), 53.74 (d, 1JPC 157.90, P-C),
62.79 (d, 2JPC 6.82, CH2), 63.20 (d, 2JPC 6.84, CH2), 64.05 (d, 3JPC 16.35,
Ph2C), 123.90 (d, 3JPC 10.38, thienyl 2-C), 126.16 (s, thienyl 5-C), 127.29,
3
127.37, 127.37, 127.91 (Ar), 127.56 (d, JPC 3.84, thienyl 4-C), 128.55,
128.72 (Ar), 137.08 (thienyl 3-C), 142.2, 143.77 (Ar); δP (CDCl3) 23.18;
EI ms: m/z 415 (M+, 3.4%).
Preparations of Aminophosphonic Acids (9):
General Procedure
Equimolar quantities (0.02–0.08 mol) of diethyl phosphite and imine (7)
were heated together as described above to give the ester (8) as a crude
oily product. Concentrated hydrochloric acid was then added (1 ml per
millimole) and the mixure was heated under reflux (3 h). By-products
were removed by extraction with toluene, the aqueous solution was
evaporated to dryness under reduced pressure, and the residue was
dissolved in methanol at 50◦C. Dropwise addition of propylene oxide
(precooled in ice) caused precipitation of the free aminophosphonic acid,
which was filtered off, washed with acetone, and recrystallized from
water and acetone (9b, 9c, 9e, 9g, and 9j), or ethanol and acetone (9f),
to give the following:
1-Amino-1-(1ꢁ-naphthyl)methanephosphonic acid (9b) (7.54 g,
31.8%), as a white solid, m.p. 257◦C (C11H12NO3P requires: C, 55.7;
H, 5.1; N, 5.9%. Found: C, 55.6; H, 5.1; N, 5.7). δH (D2O/NaOD) 4.76
(1H, d,2JPH 16.06, P-CH), 7.52–7.65 (3H, m, Ar-3H, 7H, and 8H), 7.71
3
3
(1H, d, JHH 7.45, Ar-9H), 7.84 (1H, d, JHH 8.15, Ar-6H), 7.94 (1H,
3
3
d, JHH 7.90, Ar-4H), 8.31 (1H, d, JHH 8.38, Ar-2H); δC (D2O/NaOD)
52.65 (d, JPC 131.08, P-C), 127.19, 128.34, 128.52, 128.56, 128.62,
1
129.25, 131.27, 134.23 (d, JPC 5.66), 136.06, 141.56 (Ar); δP (D2O/NaOD)
18.77; LSIMS: m/z 238 (MH+, 100).
1-Amino-1-(9ꢁ-anthryl)methanephosphonic acid (9c) (10.74 g, 37.4%),
as
a
yellow solid, m.p. 286–287◦C (decomp.) (Calculated for
C15H14NO3P: C, 62.7; H, 4.9; N, 4.9%. Found: C, 62.0; H, 5.1; N, 4.5). δH
(D2O/NaOD) 5.54 (1H, d, 2JPH 22.25, P-CH), 7.49–7.65 (4H, m, Ar-4H,
5H, 11H, and 12C), 8.04 (2H, d, 3JHH 7.30, Ar-6H, and 10H), 8.42 (1H,

Aminophosphonic Acids
1707
3
3
s, Ar-8H), 8.49 (1H, d, JHH 9.02, Ar-13H), 8.96 (1H, d, JHH 9.71, Ar-
3H); δC (D2O/NaOD) 54.32 (d, 1JPC 130.13, P-C), 127.30, 127.72, 127.78,
127.88, 129.19, 129.24, 130.96, 131.59, 131.85, 132.20, 134.09, 132.84
(d, JPC 7.48), 134.54 (d, JPC 2.77), 139.12 (Ar); δP (D2O/NaOD) 18.44;
LSIMS: m/z 288 (MH+, 11.4), 206 [MH+-(H3PO3), 34%].
1-Amino-1-piperonylmethanephosphonic acid (9e) (1.54 g, 41.6%), as
a cream solid, m.p. 242–245◦C (Calc. for C8H10NO5P: C, 41.6; H, 4.4;
N, 5.1%. Found: C, 41.1; H, 4.4; N, 5.0). δH (D2O/NaOD) 3.73 (1H, d,
2JPH8 15.18, P-CH), 5.95 (2H, s, OCH2O), 6.86–6.97 (3H, m, piperonyl
2-H, 5-H, and 6-H); δC (D2O/NaOD) 58.08 (d, 1JPC 132.46, P-C), 103.54
(OCH2O), 110.76 (d, JPC 1.82), 111.17 (d, JPC 4.59), 123.77 (d, JPC 5.79),
139.07 (d, JPC 2.33), 148.07 (d, JPC 2.83), 149.34 (d, JPC 1.89) (Ar);
δP (D2O/NaOD) 18.23; LSIMS: m/z 232 (MH+, 5.5), 150 [MH+-(H3PO3),
100].
1-Amino-4ꢁ-isopropylbenzylphosphonic acid (9f) (2.33 g, 40.7%), as a
white solid, m.p. 308◦C (decomp.) (Calc. for C10H16NO3P: C, 52.4; H,
7.0; N, 6.1%. Found: C, 52.5; H, 7.0; N, 6.0). δH (D2O/NaOD) 1.23 (6H,
d, 3JHH 6.90, 2 × CH3), 2.92 [1H, septet, (CH3)2CH], 3.79 (1H, d, 2JP-H6
15.49, P-CH), 7.29 (2H, d, Ar-3H), 7.35 (2H, dd, 3JH2−H3 8.30 and 4JP-H2
1.50, Ar-2H); δC (D2O/NaOD) 26.15 (s, 2 × CH3), 35.82 [s, (CH3)2C],
1
57.95 (d, JPC 131.58, P-C), 128.66 (d, JPC 1.38), 130.48 (d, JPC 4.90),
142.35 (d, JPC 2.45), 150.12 (d, JPC 2.64) (Ar); δP (D2O/NaOD) 18.40;
LSIMS: m/z 230 (MH+, 17.7), 148 [MH+-(H3PO3), 100].
1-Amino-4ꢁ-dimethylaminobenzylphosphonic acid (9g) (1.42 g,
41.1%), as a pale yellow solid, m.p. 230–234◦C (Calc. for C9H15N2O3P.
3/4H2O: C, 44.4; H, 6.8; N, 11.5%. Found: C, 44.9; H, 7.0; N, 11.4).
2
δH (D2O/NaOD) 2.83 (6H, s, 2 × CH3), 3.74 (1H, d, JPH 15.03, P-CH),
3
4
7.01 (2H, d, JH2−H3 8.68, Ar-3H), 7.34 (2H, dd, JP-H2 1.83, Ar-2H); δC
1
(D2O/NaOD) 44.35 (2 × CH3), 57.56 (d, JPC 132.77, P-C), 118.44 (d,
JPC 1.45), 131.21 (d, JPC 5.03), 136.27 (d, JPC 2.70), 152.64 (d, JPC 1.95)
(Ar); δP (D2O/NaOD) 18.65; LSIMS: m/z 231 (MH+, 12.3%), 149 [MH+-
(H3PO3), 100%].
1-Amino-1-(2ꢁ-thienyl)methanephosphonic acid (9j) (3.74 g, 71.5%),
as a pale pink solid, m.p. 250–252◦C [lit.38 248–250◦C (decomp.), lit.15
239–242◦C (decomp.)] (Calc. for C5H8NO3PS.1/3H2O: C, 30.2; H, 4.4; N,
7.0%. Found: C, 30.2; H, 4.4; N, 6.9). δH (D2O/NaOD) 4.19 (1H, d, 2JP-H6
3
3
15.11, P-CH), 7.04 (1H, dd, JH4−H5 5.04 and JH4−H3 3.56, thienyl 4-
H), 7.11 (1H, dd, 4JH3−H5 1.12, thienyl 3-H), 7.35 (1H, dd, thienyl 5-H);
δC (D2O/NaOD) 53.93 (d, 1JPC 133.59, P-C), 127.44 (d, 4JPC 1.38, thienyl
4-C), 128.40 (d, 3JPC 6.29, thienyl 3-C), 129.58 (d, 4JPC 1.45, thienyl 5-C),
145.94 (d, 2JPC 3.08, thienyl 2-C); δP (D2O/NaOD) 17.31; LSIMS: m/z 194
(MH+, 100%).

1708
H. R. Hudson et al.
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