A convenient one-pot synthesis of β-trifluoromethyl) allylaminophosphonic and benzylaminophosphonic acids

Article abstract of DOI:10.1080/10426500902737364

The reductive condensation of aminoalkylphosphonic acids with*β-chloro- or*β-ethylthio-(*β- trifluoromethyl)acroleins leads to secondary (trifluoromethyl) allylaminophosphonic acids in moderate to good yields. The method appears to be useful for the prepa

Full text of DOI:10.1080/10426500902737364

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Phosphorus, Sulfur, and Silicon
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A Convenient One-
Pot Synthesis of β -
(Trifluoromethyl)allylaminophospho
and Benzylaminophosphonic
Acids
Dariusz Cal a & Romuald Bartnik a
a Department of Organic and Applied Chemistry ,
University of Łódź , Łódź, Poland
Published online: 26 Mar 2009.
To cite this article: Dariusz Cal & Romuald Bartnik (2009) A Convenient One-Pot
Synthesis of β -(Trifluoromethyl)allylaminophosphonic and Benzylaminophosphonic
Acids, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:4, 1054-1064,
DOI: 10.1080/10426500902737364
To link to this article: http://dx.doi.org/10.1080/10426500902737364
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Phosphorus, Sulfur, and Silicon, 184:1054–1064, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902737364
A Convenient One-Pot Synthesis of
β-(Trifluoromethyl)allylaminophosphonic
and Benzylaminophosphonic Acids
Dariusz Cal and Romuald Bartnik
Department of Organic and Applied Chemistry, University of Lꢀ o´dz´,
Lꢀ o´dz´, Poland
The reductive condensation of aminoalkylphosphonic acids with β-chloro-
or β-ethylthio-(β-trifluoromethyl)acroleins leads to secondary (trifluoromethyl)-
allylaminophosphonic acids in moderate to good yields. The method appears to
be useful for the preparation of benzylaminophosphonic acids.
Keywords Allylaminophosphonic acids; benzylamino-phosphonic acids; reductive
amination; β-(trifluoromethyl)acroleins
INTRODUCTION
Organophosphorus compounds have found a wide range of applica-
tions in the areas of biological, medicinal, and synthetic chemistry.1,2
Aminophosphonic acids constitute an important class of compounds
that exhibit very useful properties and utilities.3 In fact, several
aminophosphonic acids are known to act as chelating agents,4 antibac-
terial agents (alafosfalin),5 herbicides (glyphosate),6 fungicides,7 en-
zyme inhibitors,8 etc. However, the highly ionic character of this class
of compounds limits transmembraned transport, and this stimulates
the research for new biologically active phosphorus compounds.9 The
introduction of fluorine atoms into the organic structure can change its
metabolic stability, binding affinity, and lipophilicity, and thus improve
its bioavailability.10 Recently, numerous fluorinated aminocarboxylic
acids were also synthesized and tested, showing increased biological
Received 9 January 2008; accepted 11 February 2008.
Dedicated to Professor Marian Mikolꢀajczyk from the CBMiM PAN in Lꢀ o´dz´, Poland,
on the occasion of his 70th birthday.
This work was supported by the Faculty of Chemistry, University of Lꢀ o´dz´.
Address correspondence to Dariusz Cal, Department of Organic and Applied
Chemistry, University of Lꢀ o´dz´, Narutowicza 68, 90-136 Lꢀ o´dz´, Poland. E-mail: darekcal@
uni.lodz.pl
1054

β-(Trifluoromethyl)allylaminophosphonic Acid
1055
activity11–13; however less attention has been paid to the synthesis of
their P-counterparts. Several fluorinated aminophosphonic acids have
already been prepared and revealed high antiviral activity14; increased
activity as insecticides, fungicides, and plant activators15; and showed
better enzyme inhibitory effect16 and stability.17,18
3-Chloro-4,4,4-trifluoro-2-phenylbutenal (1), easily available (as an
E/Z, 40:60 mixture) from the Vilsmaier reaction of 1,1,1-trifluoro-3-
phenylacetone,19 is known to be a versatile building block for the
synthesis of both acyclic and cyclic trifluoromethyl-functionalized
compounds.20–22 This acroleine can be converted into 3-ethylsulfanyl-
4,4,4-trifluoro-2-phenylbutenal (2) by reaction with ethanethiolate
(EtSH/NaH).23
In this article, we demonstrate a useful approach for applying these
two synthons for the synthesis of trifluoromethyl-functionalysed ally-
laminophosphonic acids.24
RESULTS AND DISCUSSION
It has been reported that both 1 and 2 react with primary alkyl or
arylamines to form stable 1-aza-1,3-dienes, which can be transformed
to secondary allylamines by reduction with sodium borohydride.25
We have investigated these reactions using primary aminophosphonic
acids. Starting from aminomethylphosphonic acid, chosen as a model
compound, and an equimolar amount of acroleine 1, we found that
no transformation to the imine is taking place (THF, reflux, 48 h), in
contrast to alkyl or arylamines.25 We tried to perform this reaction in
various solvents. The best result was obtained in MeOH with the ad-
dition of NEt3 (3 eq). (Aminomethyl)phosphonic acid is only partially
soluble in MeOH/NEt3 solution. After the addition of 1 (1 eq, rt, 2 h),
a clear solution was obtained. The reaction time can be shortened by
powdering of the starting amino acid. The oily residue obtained after
evaporation of the solvent from the sample was dissolved in CDCl3.
1
The H NMR spectrum exhibits a multiplet at δ 8.33–8.75 indicating
that imine CH N protons of diastereoisomers of 1-aza-1,3-diene formed
as the only product. This azadiene appeared to be not as stable as its
non-phosphorylated analogues.25 For instance, from its solution in chlo-
roform, the amino acid precipitated quantitatively after a few hours.
Next, in a one-pot procedure, we reduced the intermediate azadiene in
MeOH with sodium borohydride and isolated aminophosphonic acid 3a
as a 42:58 mixture of diastereomers (based on the 19F NMR spectrum
and confirmed by 31P NMR spectroscopy). Similarly products 3b–h were
obtained (Scheme 1, Table I).

1056
D. Cal and R. Bartnik
SCHEME 1
Encouraged by the results obtained with 1 and 2, we focused our
attention on other aldehydes. We found that in contrast to aliphatic
aldehydes, reaction with aromatic aldehydes gave very good results
(Scheme 2, Table II).
SCHEME 2
In summary, during our study on the reactivity of β-chloro
or β-ethylthio-(β-trifluoromethyl)acroleins towards aminophosphonic
TABLE I Synthesis of β-(Trifluoromethyl)allylaminophosphonic
Acids 3a–h by Reductive Amination
Diastereomers Isolated
X
Conditions Product
ratioa
yield (%) Mp (◦C)
a
b
c
Cl
Cl
Cl
Cl
CH2
(CH2)2
(CH2)3
rt, 2 h
rt, 2 h
rt, 14 h
rt, 2 h
3a
3b
3c
3d
58:42
35:65
39:61
44:56
60
38
37
56
97–102
205–207
168–171
199–200
d
e
f
g
SEt
SEt
SEt
CH2
(CH2)2
rt, 2 h
rt, 2 h
rt, 2 h
3e
3f
3g
13:87
79:21
90:10
54
42
35
193–196
172–174
194–195
h
SEt
(CH2)3
40◦C, 2.5 h
3h
8:92
65
185–187
aBased on 19F NMR.

β-(Trifluoromethyl)allylaminophosphonic Acid
1057
TABLE II Synthesis of Benzylaminophosphonic Acids 4a–e by
Reductive Amination
Isolated
yield (%)
Conditions
40 min
Product
Mp (◦C)
274–276
a
b
c
d
e
CH2
(CH2)2
PhCH
MeCH
(CH2)3
4a
45
180 min
30 min
40 min
6 h
4b
4c
4d
4e
45
60
58
71
276–279
239–241
246–247
231–233
acids, we found a simple procedure for preparation of both β-
(trifluoromethyl)allylaminophosphonic acids and benzyl functionalized
aminophoshonic acids. In contrast to the already described reductive
amination methods for aminoalkylphosphonic acids,26,27 our method
allows us to avoid chromatography and also gives good yields. Further
studies directed towards an application of the intermediate azadiene
for the synthesis of new differently functionalized aminophosphonic
acids are in progress.
EXPERIMENTAL
Melting points are uncorrected. NMR spectra were obtained with a
Bruker DPX 250, a Varian Gemini 200, and a Tesla BS 687 spec-
trometer operating at 250, 200, and 80 MHz, respectively for 1H
(TMS); 63, 50, and 20 MHz for 13C; 235 MHz for 19F (CFCl3); and
101 and 80 MHz for 31P (H3PO4). The elemental analysis was per-
formed by the Laboratory of Microanalysis of the Centre of Molecular
´ ´
and Macromolecular Studies, Polish Academy of Science in Lꢀ odz. Start-
ing acroleines 1 and 2 were obtained according to the method in the
literature.19

1058
D. Cal and R. Bartnik
β-(Trifluoromethyl)allylaminophosphonic Acids 3a–h: General
Procedure
To a suspension of the primary aminophosphonic acid (10 mmol)
in MeOH (100 mL), NEt3 (3.00 g, 30 mmol) was added, and the
mixture was stirred at room temperature for 20 min. Next, β-
(trifluoromethyl)acroleine (10 mmol), was added and stirring was con-
tinued (temperature and time are given in Table I). The clear solution
thus obtained was cooled to 0◦C, and NaBH4 (1.90 g, 50 mmol) was
added cautiously. Stirring was continued for 14 h at room temperature.
Then the solvent was evaporated, and the residue extracted with Et2O
(3 × 50 mL, 3a,b,d–g), or dissolved in MeOH (30 mL, 3c) or toluene (60
mL, 3h). If a precipitate was present, it was filtered off. Then the solvent
was evaporated (3c,h) giving an oily residue, or after concentration to
∼100 mL, petroleum ether (150 mL, 3a,b,d–g) was added to precipitate
the product. The solids or oils were dissolved in MeOH (30 mL), acidi-
fied to pH ∼2 by HCl/MeOH (4 mol/dm3), and evaporated. The residue
thus obtained was dissolved in MeOH (20 mL, 3a,d–g) or EtOH (20 mL,
3b) or acetone (40 mL, 3c,h) and filtered, and the filtrate was treated
with propylene oxide and left in a refrigerator for a few days. Products
3a–h precipitated as colorless solids, which constituted a mixture of
Z/E diastereoisomers. Aminoacids 3c,d,f required additional purifica-
tion by crystallization from a MeOH/acetone mixture (3:20).
(3-Chloro-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
methylphosphonic Acid (3a)
2
1H NMR (D2O/NaOD, 250 MHz): δ = 2.48 (d, JPH = 12.0 Hz, 2H,
2
CH2, Z or E), 2.53 (d, JPH = 12.0 Hz, 2H, CH2, Z or E), 3.82 (s, 2H,
CH2N, Z + E), 7.27–7.46 (m, 5H, C6H5, Z + E). 13C NMR (D2O/NaOD,
1
3
20 MHz): δ = 49.4 (d, JPC = 137.9 Hz, CH2, Z + E), 53.7 (dq, JPC
=
4
3
16.5 Hz, JCF = 4.0 Hz, C-1, E), 56.8 (d, JPC = 15.9 Hz, C-1, Z), 121.0
(q, 2JCF = 36.0 Hz, C-3, Z or E), 121.2 (q, 2JCF = 37.2 Hz, C-3, Z or E),
122.1 (q, 1JCF = 271.8 Hz, C-4, Z or E), 122.7 (q, 1JCF = 271.8 Hz, C-4,
Z or E), 129.3–131.2 (CHarom, Z + E), 137.9 (C-i, Z or E), 139.4 (C-i, Z
or E), 147.9 (C-2, Z or E), 149.1 (C-2, Z or E). 31P NMR (D2O/NaOD,
101 MHz): δ = 16.0, 15.9 (58 : 42). 19F NMR (D2O/NaOD, 235 MHz):
δ = −59.2, −60.0 (42 : 58). Anal. Calcd for C11H12ClF3NO3P: C, 40.08;
H, 3.67; N, 4.25%. Found: C, 40.11; H, 3.60; N, 4.27%.
2-(3-Chloro-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
ethylphosphonic Acid (3b)
1H NMR (D2O/NaOD, 250 MHz): δ = 1.35–1.52 (m, 2H, CH2, Z + E),
2.60–2.73 (m, 2H, CH2, Z + E), 3.74 (s, 2H, CH2N, Z + E), 7.23–7.47 (m,

β-(Trifluoromethyl)allylaminophosphonic Acid
1059
1
5H, C6H5, Z + E). 13C NMR (D2O/NaOD, 20 MHz): δ = 27.2 (d, JPC
=
125.1 Hz, CH2, Z + E), 46.2 (d, 2JPC = 1.8, CH2), 49.7 (q, 4JCF = 3.7 Hz,
1
C-1, E), 52.5 (C-1, Z), 121.7 (q, JCF = 274.0 Hz, C-4, Z or E), 122.3
1
2
(q, JCF = 274.0 Hz, C-4, Z or E), 124.2 (q, JCF = 36.6 Hz, C-3, Z or
E), 124.9 (q, 2JCF = 37.8 Hz, C-3, Z or E), 129.5–131.3 (CHarom, Z + E),
3
135.1 (C-i, Z or E), 136.8 (C-i, Z or E), 142.4 (q, JCF = 2.4 Hz, C-2,
Z or E), 142.8 (q, JCF = 2.0 Hz, C-2, Z or E). 31P NMR (D2O/NaOD,
3
101 MHz): δ = 19.3, 19.2 (63 : 37). 19F NMR (D2O/NaOD, 235 MHz):
δ = −59.3, −60.1 (35 : 65). Anal. Calcd for C12H14ClF3NO3P: C, 41.94;
H, 4.11; N, 4.08%. Found: C, 41.97; H, 4.15; N, 4.11%.
3-(3-Chloro-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
propylphosphonic Acid (3c)
1H NMR (D2O/NaOD, 250 MHz): δ = 1.09 (s br, 2H, CH2, Z + E),
1.33 (s br, 2H, CH2, Z + E), 3.40 (s br, 2H, CH2N, Z + E), 6.78–6.98 (m,
2
5H, C6H5, Z + E). 13C NMR (D2O/NaOD, 20 MHz): δ = 23.0 (d, JPC
=
=
4.3 Hz, CH2, Z + E), 27.9 (d, 1JPC = 130.6, CH2, Z + E), 47.9 (q, 4JCF
3.4 Hz, C-1, E), 50.4 (d, 3JPC = 14.1 Hz, CH2, Z + E), 52.9 (C-1, Z), 121.7
(q, 1JCF = 273.7 Hz, C-4, Z or E), 122.3 (q, 1JCF = 273.7 Hz, C-4, Z or E),
123.7 (q, 2JCF = 36.0 Hz, C-3, Z or E), 124.2 (q, 2JCF = 38.8 Hz, C-3, Z or
E), 129.5–131.9 (CHarom, Z + E), 135.6 (C-i, Z or E), 137.2 (C-i, Z or E),
143.3 (q, 3JCF = 2.4 Hz, C-2, Z or E), 144.0 (q, 3JCF = 1.2 Hz, C-2, Z or
E). 31P NMR (D2O/NaOD, 101 MHz): δ = 22.4. 19F NMR (D2O/NaOD,
235 MHz): δ = −59.2, −60.0 (39 : 61). Anal. Calcd for C13H16ClF3NO3P:
C, 43.65; H, 4.51%. Found: C, 43.64; H, 4.43%.
1-(3-Chloro-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
cyclopentylphosphonic Acid (3d)
1H NMR (D2O/NaOD, 250 MHz): δ = 1.29–1.97 (m, 8H, C5H8, Z + E),
3.92 (s, 2H, CH2N, Z or E), 3.97 (s, 2H, CH2N, Z or E), 7.30–7.52 (m,
3
5H, C6H5, Z + E). 13C NMR (D2O/NaOD, 20 MHz): δ = 26.3 (d, JPC
7.9 Hz, CH2, Z + E), 26.9 (d, 3JPC = 7.3 Hz, CH2, Z + E), 35.8 (d, 2JPC
7.9 Hz, CH2, Z + E), 36.5 (CH2, Z + E), 47.9 (dq, 4JCF = 1.8 Hz, 3JPC
=
=
=
5.5 Hz, C-1, E), 51.2 (d, 3JPC = 4.9 Hz, C-1, Z), 66.6 (d, 1JPC = 142.8 Hz,
2
2
Cq), 120.3 (q, JCF = 36.0 Hz, C-3, Z or E), 120.5 (q, JCF = 37.8 Hz,
1
1
C-3, Z or E), 122.2 (q, JCF = 273.4 Hz, C-4, Z or E), 122.8 (q, JCF
=
274.3 Hz, C-4, Z or E), 129.4–130.4 (CHarom, Z + E), 138.1 (C-i, Z or E),
139.5 (C-i, Z or E), 148.5 (C-2, Z or E), 149.4 (C-2, Z or E). 31P NMR
(D2O/NaOD, 101 MHz): δ = 23.0, 22.8 (56 : 44). 19F NMR (D2O/NaOD,
235 MHz): δ = −59.4, −60.1 (44 : 56). Anal. Calcd for C15H18ClF3NO3P:
C, 46.95; H, 4.73%. Found: C, 46.91; H, 4.91%.

1060
D. Cal and R. Bartnik
(3-Ethylsulfanyl-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
metylphosphonic Acid (3e)
1H NMR (D2O/NaOD, 250 MHz): δ = 1.02 (t, 3JHH = 7.4 Hz, 3H, CH3,
Z or E), 1.28 (t, 3JHH = 7.3 Hz, 3H, CH3, Z or E), 2.45 (d, 2JPH = 12.6 Hz,
3
2H, CH2, Z + E), 2.85 (q, JHH = 7.4 Hz, 2H, CH2, Z + E), 3.83 (s, 2H,
CH2, Z or E), 4.03 (s, 2H, CH2, Z or E), 7.22–7.44 (m, 5H, C6H5, Z + E).
13C NMR (D2O/NaOD, 20 MHz): δ = 11.6 (CH3, Z or E), 12.0 (CH3, Z or
1
E), 27.1 (SCH2, Z or E), 27.8 (SCH2, Z or E), 46.0 (d, JPC = 137.2 Hz,
CH2, Z + E), ), 51.4 (dq, 3JPC = 17.4 Hz, 4JCF = 3.0 Hz, C-1, E), 54.4 (d,
3JPC = 14.0 Hz, C-1, Z), 120.5 (q, 2JCF = 30.8 Hz, C-3, Z + E), 121.5 (q,
1JCF = 275.5 Hz, C-4, Z + E), 125.6–128.1 (CHarom, Z + E), 136.3 (C-i,
Z or E), 137.4 (C-i, Z or E), 156.2 (C-2, Z + E). 31P NMR (D2O/NaOD,
101 MHz): δ = 16.1. 19F NMR (D2O/NaOD, 235 MHz): δ = −55.6, −55.7
(13 : 87). Anal. Calcd for C13H17F3NO3PS: C, 43.95; H, 4.82%. Found:
C, 43.87; H, 4.99%.
2-(3-Ethylsulfanyl-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
ethylphosphonic Acid (3f)
3
1H NMR (D2O/NaOD, 250 MHz): δ = 1.01 (t, JHH = 7.4 Hz, 3H,
3
CH3, Z or E), 1.29 (t, JHH = 7.4 Hz, 3H, CH3, Z or E), 1.77–1.95 (m,
3
3
2H, CH2P), 2.52 (q, JHH = 7.4 Hz, 2H, CH2, Z or E), 2.90 (q, JHH
=
7.4 Hz, 2H, CH2, Z or E), 3.15–3.28 (m, 2H, CH2), 4.34 (s, 2H, CH2, Z
or E), 4.59 (s, 2H, CH2, Z or E), 7.31–7.51 (m, 5H, C6H5, Z + E). 13C
NMR (D2O/NaOD, 20 MHz): δ = 14.8 (CH3, Z or E), 15.3 (CH3, Z or
1
E), 30.2 (SCH2, Z or E), 31.0 (SCH2, Z or E), 31.2 (d, JPC = 127.0 Hz,
4
CH2, Z + E), ), 52.3 (q, JCF = 3.0 Hz, C-1, E), 55.8 (C-1, Z), 124.0 (q,
2JCF = 30.5 Hz, C-3, Z or E), 124.8 (q, JCF = 30.5 Hz, C-3, Z or E),
2
125.0 (q, 1JCF = 275.3 Hz, C-4, Z or E), 125.5 (q, 1JCF = 275.3 Hz, C-4,
Z or E), 128.9–130.5 (CHarom, Z + E), 139.8 (C-i, Z or E), 140.9 (C-i, Z
or E), 159.5 (q, 3JCF = 2.4 Hz, C-2, Z or E), 159.9 (q, 3JCF = 2.4 Hz, C-2,
Z or E). 31P NMR (D2O/NaOD, 101 MHz): δ = 18.3, 18.2 (78 : 22). 19F
NMR (D2O/NaOD, 235 MHz): δ = −56.3, −56.6 (79 : 21). Anal. Calcd
for C14H19F3NO3PS: C, 45.53; H, 5.19%. Found: C, 45.37; H, 5.12%.
1-(3-Ethylsulfanyl-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
cyclohexylphosphonic Acid (3g)
1H NMR (D2O/NaOD, 250 MHz): δ = 0.94–1.58 (m, 13H, C6H10
+
=
3
3
CH3, Z + E), 2.52 (q, JHH = 7.4 Hz, 2H, CH2, Z or E), 2.86 (q, JHH
7.4 Hz, 2H, CH2, Z or E), 3.98 (s, 2H, CH2, Z or E), 4.14 (s, 2H, CH2, Z
or E), 7.29–7.45 (m, 5H, C6H5, Z + E). 13C NMR (D2O/NaOD, 20 MHz):
δ = 14.9 (CH3, Z or E), 15.3 (CH3, Z or E), 21.5 (d, 3JPC = 9.2 Hz,CH2,
Z + E), 26.1 (CH2, Z or E), 26.5 (CH2, Z or E), 30.3 (CH2, Z or E), 31.1

β-(Trifluoromethyl)allylaminophosphonic Acid
1061
4
(CH2, Z or E), 31.8 (CH2, Z or E), 47.7 (q, JCF = 3.5 Hz, C-1, E), 50.5
(C-1, Z), 58.7 (d, 1JPC = 141.6 Hz, Cq, Z + E), 124.0 (q, 2JCF = 30.5 Hz,
C-3, Z + E), 124.9 (q, 1JCF = 275.3 Hz, C-4, Z + E), 129.3–131.8 (CHarom
,
Z + E), 139.5 (C-i, Z or E), 159.3 (C-2, Z + E). 31P NMR (D2O/NaOD,
101 MHz): δ = 22.1, 21.9 (91 : 9). 19F NMR (D2O/NaOD, 235 MHz):
δ = −55.5, −55.6 (90 : 10). Anal. Calcd for C18H25F3NO3PS: C, 51.06;
H, 5.95%. Found: C, 50.90; H, 5.73%.
3-(3-Ethylsulfanyl-4,4,4-trifluoro-2-phenylbut-2-enylamino)-
propylphosphonic Acid (3h)
1H NMR (D2O/NaOD, 250 MHz): δ = 1.00 (t, 3JHH = 7.4 Hz, 3H, CH3,
Z or E), 1.14–1.28 (m, 5H, CH2+ CH3, Z + E), 1.40–1.52 (m, 2H, CH2N,
Z + E), 2.47(t, 3JHH = 7.2 Hz, 2H, CH2, Z + E), 2.81 (q, 3JHH = 7.4 Hz,
3H, SCH2, Z + E), 3.74 (s, 2H, CH2, Z or E), 3.95 (s, 2H, CH2, Z or
E), 7.21–7.43 (m, 5H, C6H5, Z + E). 13C NMR (D2O/NaOD, 20 MHz):
2
δ = 14.8 (CH3, Z or E), 15.3 (CH3, Z or E), 24.0 (d, JPC = 3.1 Hz,
1
CH2), 28.3 (d, JPC = 130.6 Hz, CH2, Z + E), 30.1 (SCH2, Z or E), 30.9
(SCH2, Z or E), 50.7 (d, 3JPC = 15.9 Hz, CH2, Z + E), 54.6 (C-1, Z + E),
1
2
124.9 (q, JCF = 275.9 Hz, C-4, Z + E), 127.1 (q, JCF = 31.1 Hz, C-3,
Z + E), 129.1–130.9 (CHarom, Z + E), 138.1 (C-i, Z or E), 139.4 (C-i, Z or
E), 155.8 (C-2, Z + E). 31P NMR (D2O/NaOD, 101 MHz): δ = 22.3. 19F
NMR (D2O/NaOD, 235 MHz): δ = −55.5, −55.7 (8 : 92). Anal. Calcd for
C15H21F3NO3PS: C, 47.00; H, 5.52%. Found: C, 46.78; H, 5.45%.
Benzylaminophosphonic Acids 4a–e: General Procedure
To the suspension of primary aminophosphonic acid (10 mmol) in
MeOH (100 mL), NEt3 (3.00 g, 30 mmol) was added, and the solution
was stirred at room temperature for 20 min. Next, the aromatic alde-
hyde (10 mmol) was added, and stirring was continued at room temper-
ature (time is given in Table II). The clear solution thus obtained was
cooled to 0◦C, and NaBH4 (1.90 g, 50 mmol) was added cautiously. Stir-
ring was continued for 14 h at room temperature. Then the solvent was
evaporated, and the residue treated with toluene (60 mL, 4a,c) or water
(30 mL, 4b,d,e), stirred for 5 min, and the solvent was evaporated. The
residue thus obtained was dissolved in MeOH (30 mL, 4a,c) or water
(30 mL, 4b,d,e), acidified to pH ∼2 by HCl/MeOH (4 mol/dm3, 4a,c) or
by HCl/H2O (4 mol/dm3, 4b,d,e), and evaporated. For the preparation
of 4d, the residue was crystallized from water and washed with MeOH
providing the product as colorless crystals. For 4a–c,e the residue was
dissolved in MeOH/acetone (2:1, 50 mL, 4a), MeOH (50 mL, 4b,c), or
EtOH/acetone (1:1, 30 mL, 4e). The precipitate, if present, was filtered

1062
D. Cal and R. Bartnik
off, and the filtrate was treated with propylene oxide and left in the
refrigerator for 12 h. Products 4a–c,e precipitated as white colorless
solids. All products gave satisfactory spectroscopic data in accord with
the assigned structures.
(Benzylamino)methylphosphonic Acid (4a)
2
1H NMR (D2O/NaOD, 250 MHz): δ = 2.54 (d, JPH = 12.5 Hz,
2H, CH2), 3.74 (s, 2H, CH2), 7.30–7.35 (m, 5H, C6H5). 13C NMR
1
(D2O/NaOD, 20 MHz): δ = 47.7 (d, JPC = 130.6 Hz, CH2), 54.9 (d,
3JPC = 12.8 Hz, CH2), 130.4–131.1 (CHarom), 135.9 (C-i). 31P NMR
(D2O/NaOD, 80 MHz): δ = 15.7. Anal. Calcd for C8H12NO3P: C, 47.77;
H, 6.01; N, 6.96%. Found: C, 47.54; H, 6.11; N, 6.88%.
2-(4-Chlorobenzylamino)ethylphosphonic Acid (4b)
1H NMR (D2O/NaOD, 250 MHz): δ = 1.56–1.72 (m, 2H, CH2), 2.96–
3.09 (m, 2H, CH2), 3.96 (s, 2H, CH2), 7.10–7.50 (m, 4H, C6H4). 13C
NMR (D2O/NaOD, 50 MHz): δ = 30.6 (d, 1JPC = 124.4 Hz, C-1), 48.4 (C-
2), 133.1 (CHarom), 134.9 (CHarom), 136.3 (Cqarom), 138.1 (Cqarom). 31P
NMR (D2O/NaOD, 80 MHz): δ = 18.5. Anal. Calcd for C9H13ClNO3P:
C, 43.30; H, 5.25; N, 5.61%. Found: C, 43.15; H, 5.23; N, 5.62%.
Phenyl(thiophen-2-ylmethylamino)methylphosphonic Acid
(4c)
1H NMR (D2O/NaOD, 250 MHz): δ = 3.60 (AB, J = 14.1 Hz, 1H,
2
CH), 3.64 (d, JPH = 7.8 Hz, 1H, CH), 3.74 (AB, J = 13.9 Hz, 1H, CH),
6.80–6.89 (m, 2H, CHarom), 7.18–7.32 (CHarom). 13C NMR (D2O/NaOD,
3
1
63 MHz): δ = 43.2 (d, JPC = 12.6 Hz, CH2), 60.4 (d, JPC = 131.2 Hz,
CH), 124.2–127.3 (CHarom), 136.7 (Cqarom), 137.9 (Cqarom). 31P NMR
(D2O/NaOD, 101 MHz): δ = 16.0. Anal. Calcd for C12H14NO3PS: C,
50.88; H, 4.98; N, 4.94%. Found: C, 50.74; H, 5.01; N, 4.97%.
1-(Benzylamino)ethylphosphonic Acid (4d)
1H NMR (D2O/NaOD, 80 MHz): δ = 1.44 (dd, 3JHH = 7.2 Hz, 3JPH
=
3
2
13.6 Hz, 3H, CH3), 3.09 (dq, JHH = 7.2 Hz, JPH = 12.7 Hz, 1H, CH),
4.28 (s, 2H, CH2), 7.52 (s, 5H, C6H5). 13C NMR (D2O/NaOD, 50 MHz):
3
1
δ = 17.1 (C-2), 54.0 (d, JPC = 6.5 Hz, CH2), 56.5 (d, JPC = 133.4
Hz, C-1), 132.9–133.5 (CHarom), 137.5 (Cqarom). 31P NMR (D2O/NaOD,
80 MHz): δ = 18.1. Anal. Calcd for C9H14NO3P: C, 50.23; H, 6.56; N,
6.51%. Found: C, 50.14; H, 6.48; N, 6.65%.

β-(Trifluoromethyl)allylaminophosphonic Acid
1063
3-(Quinolin-2-ylmethylamino)propylphosphonic Acid (4e)
1H NMR (D2O/NaOD, 250 MHz): δ = 1.15–1.29 (m, 2H, CH2), 1.47–
1.59 (m, 2H, CH2), 2.45 (t, 3JHH = 7.3 Hz, 2H, CH2), 3.77 (s, 2H, CH2),
7.29–8.09 (m, 6H, CHarom). 13C NMR (D2O/NaOD, 63 MHz): δ = 21.4
(C-2), 25.2 (d, 1JPC = 130.2 Hz, C-1), 47.9 (d, 3JPC = 17.6 Hz, C-3), 51.3
(CH2), 117.1–155.2 (Carom). 31P NMR (D2O/NaOD, 101 MHz): δ = 22.3.
Anal. Calcd for C13H17N2O3P: C, 55.71; H, 6.11; N, 10.00%. Found: C,
55.67; H, 6.09; N, 9.98%.
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