An efficient one-pot synthesis of new polyfunctional phosphorus acid amphiphiles

Article abstract of DOI:10.1002/(SICI)1099-0690(200001)2000:2<281::AID-EJOC281>3.0.CO;2-2

The addition reaction between the P-H bond of tetraoxyspirophosphoranes 1-2 and long-chain imines 3a-h (decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, and oleyl imines) occurs instantaneously at room temperature. It is diastereoselective, and quantitatively leads to the corresponding (α- aminoalkyl)spirophosphoranes 4a-h and 5e. The influence of the pentacoordinated phosphorus atom on the stereoselectivity of the Pudovik reaction might be attributed to the involvement of the rigid spirophosphoranide (P(v)) intermediate in the addition reaction. Selective and one- pot hydrolysis of these P-C bond spirophosphoranes readily proceeds either at room temperature in the presence of moist solvents to give the corresponding carboxyalkyl (α-aminoalkyl)phosphonic acid monoesters 6a-h and 7e, or the reaction may be carried out in the presence of 20% aqueous hydrochloric acid under reflux, to afford the free (α-aminoalkyl)phosphonic acid amphiphiles 8a-h in high yields. In contrast to their sodium salts, these single- and double-chained free and monoester phosphonic acid amphiphiles exist as zwitterions and are not soluble in water.

Full text of DOI:10.1002/(SICI)1099-0690(200001)2000:2<281::AID-EJOC281>3.0.CO;2-2

FULL PAPER
An Efficient One-Pot Synthesis of New Polyfunctional Phosphorus
Acid Amphiphiles
[a]
[a]
[a]
´
Karine Vercruysse, Christophe Dejugnat, Aurelio Munoz,
and Guita Etemad-Moghadam*[a]
Keywords: Phosphorus acid amphiphiles / (α-Aminoalkyl)phosphonic acids / Carboxyalkyl (α-aminoalkyl)phosphonic
acid monoesters / Spirophosphorane / Pudovik reaction
The addition reaction between the P–H bond of
tetraoxyspirophosphoranes 1–2 and long-chain imines 3a–h
(decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, and oleyl
pot hydrolysis of these P–C bond spirophosphoranes readily
proceeds either at room temperature in the presence of moist
solvents to give the corresponding carboxyalkyl (α-
imines) occurs instantaneously at room temperature. It is aminoalkyl)phosphonic acid monoesters 6a–h and 7e, or the
diastereoselective, and quantitatively leads to the
reaction may be carried out in the presence of 20% aqueous
corresponding (α-aminoalkyl)spirophosphoranes 4a–h and
hydrochloric acid under reflux, to afford the free (α-
5e. The influence of the pentacoordinated phosphorus atom aminoalkyl)phosphonic acid amphiphiles 8a–h in high yields.
on the stereoselectivity of the Pudovik reaction might be
attributed to the involvement of the rigid spirophosphoranide
(PV) intermediate in the addition reaction. Selective and one-
In contrast to their sodium salts, these single- and double-
chained free and monoester phosphonic acid amphiphiles
exist as zwitterions and are not soluble in water.
drolytic cleavage of diester precursors, partial esterification
of phosphonic diacids, or oxidation of α-aminophosphinic
acid precursors.[16]
We have continued our investigations into the reactivity
of the PϪH-labile phosphorus derivatives[17][18] and the
synthesis of new α-functionalized phosphorus amphi-
philes,[19] and we wish to report here the reactivity of spiro-
phosphoranes towards long-chain imines, and their one-pot
and selective hydrolysis to result in (α-aminoalkyl)phosph-
orus acid amphiphiles.
The presence of hydrophobic substituents is expected to
widen their application field, because their coordinating
and biological properties should be enhanced by the co-
existence of hydrophilic and hydrophobic groups in one
molecule. Long-chain phosphonate esters were therefore
evaluated as enhancers of the transdermal penetration of
drugs,[20] and as new ionic membrane carriers for the trans-
port of metal ions or amino acids through lipophilic mem-
branes in biological systems.[21] Benzylaminophosphonic
acids were reported to be potent inhibitors of human pros-
tatic acid phosphatase; their affinity for the enzyme-active
site was attributed to their highly hydrophobic character.[3c]
Metal phosphonates are also able to form layered com-
pounds with magnetic and electronic properties, which may
be modulated by interlayer interactions through the choice
of the organic moieties and the inclusion of suitable func-
tional groups.[22]
Introduction
The phosphorus analogs of α-aminocarboxylic acids, (α-
aminoalkyl)phosphorus acids (phosphonic acids, esters, and
salts) have attracted significant attention owing to their syn-
thetic and biological value as both agrochemical (herbi-
cides, pesticides, growth regulator in plants) and medicinal
(antibiotics, antivirals, enzyme inhibitors) products with
broad applications.[1Ϫ3] Platinum complexes with phos-
phonocarboxylate ligands show promising antitumor ac-
tivity.[4] Their usefulness as corrosion inhibitors[5] and as
flame-retardants for some polymers[6] has also been de-
scribed. The metal-ion-coordinating properties of (aminoal-
kyl)phosphonic acids were looked at more intensively in re-
cent years, to arrive at a better understanding of their bio-
logical activity (inhibition of metalloenzymes, metabolic
regulation, etc.).[7] Thus, there has been increasing activity
in the study of the chemistry of phosphonates,[8] and the
development of new methodologies for their preparation is
still of great interest.
The bioactivity of these compounds is known to be
strongly dependent on their absolute configurations, and
numerous methods, including diastereomeric[9] and chemo-
enzymatic[10] resolutions and asymmetric synthesis,[11Ϫ14]
are available for the synthesis of optically pure aminophos-
phonic acids. Of the various methods for the preparation of
(α-aminoalkyl)phosphonic acids, the most general route is
the Pudovik addition of dialkylphosphonate to a Schiff
base, followed by hydrolytic or reductive cleavage of diester
precursors.[15] In contrast, the synthesis of their monoesters
is more delicate, and requires partial hydrolytic or nonhy-
Results and Discussion
Spirophosphoranes with a PϪH-labile bond are well
documented as useful models for mimicking the pentacoor-
dinate transition states or intermediates in phosphate ester
hydrolysis.[23] It is already known that tetraoxyspirophos-
[a]
´
Laboratoire des IMRCP (UMR 5623), Universite Paul Sabatier,
ˆ
118, Route de Narbonne Ϫ Bat. 2R1,
F-31062 Toulouse cedex 04, France
E-mail: etemad@ramses.ups-tlse.fr
Eur. J. Org. Chem. 2000, 281Ϫ289
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0202Ϫ281 $ 17.50ϩ.50/0
281

´
K. Vercruysse, C. Dejugnat, A. Munoz, G. Etemad-Moghadam
FULL PAPER
phoranes that bear a PϪH bond are reactive towards
The addition reaction of equimolar amounts of spiropho-
alkynes,[24] imines,[25] enamines,[26] and aldehydes.[27] How- sphorane 1؊2 to long-chain imines 3a؊h in anhydrous di-
ever, their use as chiral reagents in the development of new chloromethane occurs instantaneously at room tempera-
stereoselective methods is rarer. The asymmetric addition ture, and stereoselectively and quantitatively gives the (α-
reaction between a tricyclic chiral phosphorane and an acti- aminoalkyl)spirophosphoranes 4a؊h and 5e, which contain
vated carbonyl compound leads to rearranged alkoxyphos- a P*ϪC* bond. The high selectivity of the reaction results
phoranes with high stereoselectivity.[28] More recently, the from the asymmetric induction during the formation of the
synthetic utility of spirooxyphosphoranyl C anions as valu- PϪC bond (Scheme 1).
able intermediates in HornerϪEmmons olefination chemis-
The spirophosphoranes 4a؊h and 5e, containing a PϪC
bond, have two stereogenic centers: (1) the pentacoordi-
try was reported.[29]
For this work, we selected the tetraoxyspirophosphoranes nated phosphorus atom and (2) the carbon bonded to the
1Ϫ2, whose two mixed anhydride functions [C(O)ϪOϪP] phosphorus atom; these compounds exist as two dia-
are highly electron-withdrawing and are more apicophilic stereomeric pairs of enantiomers (Table 1). The 31P NMR
than the ethereal PϪOϪC oxygen atoms are; this ensures a spectra of the two diastereomers of 4a؊h and 5e are charac-
strong preference for the axial orientation of the carboxy terized by two high-field signals at approximately δ ϭ
groups in the trigonal bipyramidal arrangement of substitu- Ϫ31 (2JPH ഠ 25 Hz), confirming the preservation of the
ents attached to phosphorus.[23][30] As a consequence, the (PV) substructure. The signals of the two diastereomers are
spirophosphoranes 1؊2: (i) are made up of a smaller num- separated by approximately 1 ppm. The major isomer, with
2
ber of stereoisomers, due to the high barrier of the stereo- the larger JPH coupling constant, is the most deshielded
mutation process, (ii) have phosphorus atoms that are more one. Replacement of the phenyl by an aliphatic alkyl group
Lewis acidic, and (iii) have PϪH bonds with enhanced acid- (R2 ϭ Me, undecyl) causes deshielding of the 31P signal by
ity.[30Ϫ32] Moreover, 1؊2 exhibit a strong preference for the approximately 5 ppm. The chemical shift of the carbon
spirophosphoranide (PV) substructure A (Scheme 1) in atom adjacent to the phosphorus atom (13C δ ഠ 67) and
basic media (e.g., DMF/Et3N). This is in contrast to the the coupling constant (1JCP ഠ 190 Hz) are consistent with
spirophosphoranes derived from substituted glycols (meth- the presence of an (α-aminoalkyl)spirophosphorane moiety.
ylene group in lieu of carbonyl), for which the tautomeric The methine proton resonance appears in most cases as a
PIII/PV chain-ring equilibria, involving the migration of a doublet at approximately δ ϭ 4Ϫ5 (2JHP ഠ 25 Hz). 31P-,
proton, are greatly favor of the tricoordinated form 13C-, and 1H NMR analysis show that the two dia-
(PIII).[23][33] Consequently, the rigidity of the PV substruc- stereomers are present in most cases. Their relative ratios,
ture of 1Ϫ2, added to the strong acidity of the PϪH bond determined by 31P NMR spectroscopy, are nearly identical
1
[pKDMF (1) ϭ 4.0][30] should allow stereoselective conden- to the values obtained from H NMR data (Table 1).
sation with prochiral imines 3a؊h.
The diastereoselectivity of the addition reaction is depen-
The nonplanarity of spirophosphoranes 1Ϫ2 results in dent on the nature of the α-substituent of the phosphorus
their chirality, with the phosphorus atom as a stereogenic atom, since for R2 ϭ Ph, and regardless of the length of the
center.[34] The 31P NMR spectra of 1Ϫ2 contain a single long-chain (n ϭ 10Ϫ18), the diastereomeric excess is high
high-field signal with a large coupling constant [1 (R1 ϭ (4a؊f: 90:10 Ն ratio Ն 80:20). In contrast, substitution by
1
Me): 31P δ ϭ Ϫ50.4; JPH ϭ 920 Hz; 2 (R1 ϭ Ph): 31P δ ϭ methyl instead of phenyl results in decreasing diastereosel-
1
Ϫ50.5; JPH ϭ 917 Hz], characteristic of pentacoordinated ectivity of the reaction (4g: ratio ϭ 65:35). This can be attri-
phosphorus compounds and corresponding to a racemic buted to: (i) the steric hindrance of the phenyl group during
mixture.
the addition reaction, promoting the preferential attack of
Scheme 1. Diastereoselective synthesis of the PϪC-bond (α-aminoalkyl)spirophosphoranes
282
Eur. J. Org. Chem. 2000, 281Ϫ289

One-Pot Synthesis of New Polyfunctional Phosphorus Acid Amphiphiles
FULL PAPER
Table 1. Diastereomeric ratio of (α-aminoalkyl)spirophosphoranes 4, isolated yields of phosphonic acid monoesters 6 and phosphonic
acids 8, and their characteristic NMR parameters
[c]
[d]
[d]
Compd.
R1
R2
CH3(CH2)nϪ1
(%)[a,b]
31P: δ (2JPH
)
13C: δ (1JCP
)
1H: δ (2JHP
)
4a؊f
Me
Me
Ph
n ϭ 10Ϫ18
n ϭ 18
80Ϫ90[a]
10Ϫ20[a]
65[a]
Ϫ31 (25)
Ϫ33 (21)
Ϫ25.9 (24)
Ϫ26.2 (m)
9 (17)
67 (190)
69 (180)
58 (194)
62 (184)
62 (146)
52 (150)
62 (137)
53 (140)
4.4 (25)
4.5 (21)
3.3 (m)
4g
Me
35[a]
6a؊h
6g
8a؊h
8g
Me
Me
Ϫ
Ph
n ϭ 10Ϫ18
n ϭ 18
n ϭ 10Ϫ18
n ϭ 18
74Ϫ96[b]
80[b]
4.7 (17)
3.3 (m)
4.6 (17)
3.5 (m)
Me
Ph
12 (15)
66Ϫ92[b]
79[b]
12 (17)
15 (m)
Ϫ
Me
[a]
1
Diastereomeric ratio of 4aϪf and 4g determined by 31P and H NMR analysis of the reaction mixture (the accuracy of the measure-
ments is within ±5%). Ϫ Isolated yields of the phosphonic acid monoesters 6 and phosphonic acids 8. Ϫ [c] 31P NMR spectra of the
[b]
reaction mixture in CDCl3; J in Hz. Ϫ [d] 13C and H NMR data of the methine group α to the phosphorus atom, measured in CDCl3
1
for 4 and in CD3COOD for 6 and 8; J in Hz.
1 upon one face of the imine, (ii) the inductive effect of the ist as a pair of enantiomers indistinguishable by NMR
phenyl group which enhances the electrophilic character of analysis. Their 31P NMR spectra are characterized by
the imineЈs carbon atom towards nucleophilic attack of 1, chemical shifts around δ ϭ 8; this shows that the P nucleus
1
and (iii) the syn/anti isomerism of the imine (the H NMR is deshielded by approximately 40 ppm relative to that of
spectra of 3g shows the presence of two isomers, whereas 4a؊h and 5e. This is consistent with the conversion of a
no isomerism is observed for the imines 3a؊f derived pentacoordinated phosphorus atom into a tetracoordinated
from benzaldehyde).
phosphorus atom (Table 1). As for (α-aminoalkyl)spiropho-
To account for the high diastereofacial selectivity of the sphoranes, their 31P chemical shift is sensitive to the nature
spirophosphorane addition to the Shiff base, we propose a of the α-substituent, since for alkyl substituents (R2 ϭ Me,
reaction mechanism proceeding through the spirophospho- undecyl) instead of phenyl, a shielding of the phosphorus
ranide intermediate A, followed by the nucleophilic attack nucleus by approximately 3Ϫ4 ppm takes place. The chemi-
of this pentacoordinated anion at the electrophilic carbon cal shift of the α-carbon (δ(13C) ഠ 62) does not change
atom of imine to afford the (α-aminoalkyl) spirophosphor- significantly [∆δ(13C) ഠ 5 ppm], but the coupling with
anes 4a؊e and 5e. The rigidity of the spirophosphoranide phosphorus (1JCP ഠ 145 Hz) is smaller, by about 45 Hz,
intermediate is the decisive stereochemical factor (Scheme than that of (α-aminoalkyl)spirophosphoranes 4a؊h and
1). Moreover, the reaction occurs instantaneously at room 5e. We observed the same chemical shift for the methine
temperature, and avoids the reversibility of the addition re- proton in 6؊7 (related to 4؊5), but the coupling constant
1
action observed for other spirophosphoranes.[25]
2JHP ഠ 18 Hz decreased by approximately 7 Hz. The H
NMR spectra of 6a؊h show that the methyl groups of the
monoestersЈs lateral chain are nonequivalent due to the
asymmetric center.
The (α-aminoalkyl)spirophosphoranes 4a؊h and 5e are
stable in solution and under argon for one week; they can
be readily and selectively transformed, in situ, at room tem-
perature in the presence of moist solvents, e.g., acetonitrile/
The reaction of spirophosphoranes 1؊2 with imines, fol-
water, and in good yields, into carboxyalkyl (α-aminoalkyl)- lowed by the in situ hydrolysis of the (α-aminoalkyl)spiro-
phosphonic acid monoesters 6a؊h and 7e (Scheme 2, path- phosphorane intermediates, is therefore general, and can be
way A).
applied to long-chain imines derived from aromatic and ali-
The (α-aminoalkyl)phosphonic acid monoesters 6؊7 phatic aldehydes and long-chain amines. This affords poly-
have only one stereogenic center (α-carbon atom). They ex- functional phosphonic acid monoesters bearing α-amino
Scheme 2. Selective and one-pot synthesis of free or monoester (α-aminoalkyl)phosphonic acid amphiphiles from PϪH-bond spirophos-
phorane and long-chain imines
Eur. J. Org. Chem. 2000, 281Ϫ289
283

´
K. Vercruysse, C. Dejugnat, A. Munoz, G. Etemad-Moghadam
FULL PAPER
2
and β-carboxylic acid groups. Apart from their several ap- Table 2. Influence of pH on the δ31P and JPH (Hz) values of the
plications,[1][5] complexes of these monoesters with metals
are characterized by their limited oligomerization ability, in
(α-aminoalkyl)phosphonic acid monoester 6e in water, at 20°C (c ϭ
0.35 ⁾
contrast to aminophosphonic acids and their diesters that,
in the presence of transition metal ions, have the disadvan-
tage of polymerizing.[16a]
Moreover, it has recently been demonstrated that the
good crosslinking ability of phosphonocarboxylic acids for
cellulose is related to the presence of a β-COOH func-
tion.[35]
pH
δ (31P)
2JPH (Hz)
1.7[a]
7.5
10.8
13.0
8.7
17.2
br. m
20.6
19.3
10.9
12.7
16.5
[a]
6e in 20% aqueous acetic acid.
The synthesis of (α-aminoalkyl)phosphonic acids 8a؊h
can be achieved either by one-pot hydrolysis of 4a؊h and
5e in the presence of 20% aqueous hydrochloric acid under synthesis of a new series of single-chain and double-chain
reflux for 10 h (Scheme 2, pathway B), or by hydrolysis of phosphonic acid amphiphiles as free acids or as carboxyal-
carboxyalkyl (α-aminoalkyl)phosphonic acid monoesters kyl monoesters. Our study shows that the pentacoordinated
6a؊h and 7e under the same conditions (Scheme 2, path- phosphorus atom is able to exert a strong influence on the
way C). Both methods afford 8 as a crystalline white pow- stereochemistry of carbonϪphosphorus bond formation in
der in good yields. The 31P chemical shifts of 8 exhibit slight the Pudovik reaction, due to the involvement of the spiro-
deshielding of the 31P nucleus with respect to monoesters phosphoranide (PV) intermediate. The spirophosphoranic
6؊7 [∆δ(31P) ഠ 5] whereas no noticeable variations are ob- substructure can be considered to be a chiral auxiliary: it
1
served for H and 13C NMR spectra except for a decrease induces asymmetry and is then removed by being converted
in the coupling constant ∆1JCP ഠ 10 Hz.
into tetracoordinated phosphonic acid derivatives. Owing
The phosphonic acid monoesters 6؊7 and the free phos- to its easy implementation, this method has broad synthetic
phonic acids 8 are not soluble in water and, to a great ex- utility, and we are currently investigating the enantioselec-
tent, precipitate from the reaction mixture during the reac- tive version of the addition of chiral spirophosphoranes to
tion. These acids probably exist as zwitterions with three imines, our main aim being the synthesis of optically pure
titratable protons: a strongly dissociated proton (PϪOH) phosphorus analogs of amino acids. The aggregation be-
and two weakly dissociated ones (COOH and NH). In con- havior of these new α-functionalized amphiphiles is under
trast, their sodium salts, obtained from cationic exchange investigation.
resins, are soluble in water, and their 31P chemical shifts
show, as expected, a weak deshielding [∆δ(31P) ഠ 5] com-
pared to the acid precursors.
Experimental Section
As in amino- and hydroxy-substituted phosphonic acid
General: Spectra were recorded with the following instruments: IR
compounds,[2b,19,36] the 31P chemical shifts of the carboxyal-
spectra: PerkinϪElmer IRFT 1600; 1H, 13C and 31P spectra: Bruker
kyl (α-aminoalkyl)phosphonic acid monoesters 6؊7 and
AC80, AC200 or 250WM; mass spectra by chemical ionization
the free (α-aminoalkyl)phosphonic acids 8 are strongly de-
pendent on the pH of the solution. The insolubility of the
long-chain (α-aminoalkyl)phosphorus acids in water, DMF,
or DMSO prevents the determination of their pK values.
Thus, the measurements are realized from the water-soluble
6e disodium salt in distilled water (c ϭ 0.35 , pH ϭ 10.8).
Addition of concentrated sodium hydroxide solution or hy-
drochloric acid to this solution led to pH values of 13 and
7.5, respectively. For more acidic solutions it is not possible
to determine the pH accurately since the product precipi-
tates. An increase of the pH of the solution (about 10 pH
units) causes a deshielding of the phosphorus nucleus by
approximately 7 ppm without significant modification of
(DCI/NH3 or DCI/CH4) or positive FAB modes: Nermag
R10Ϫ10H. Ϫ Elemental analyses were performed by the Microana-
lytical Service Laboratory of the “Laboratoire de Chimie de Coor-
dination” of Toulouse. Ϫ Long-chain amines (C10ϪC18), benzal-
dehyde, acetaldehyde, dodecylaldehyde, phosphorus trichloride, 2-
hydroxyisobutyric acid, benzilic acid (Aldrich), and oleylamine
(Acros) were used as received without further purification. Di-
˚
chloromethane, reagent grade product, was maintained over 4 A
molecular sieves and stored in a dark bottle protected from moist-
ure. Ϫ The spirophosphoranes 1؊2 were prepared according to the
procedure already described.[31]
General Procedure for the Synthesis of Schiff Bases (3a؊h): Equim-
olar amounts of amine and aldehyde in anhydrous dichlorometh-
˚
ane were stirred at 40 °C for 6 h in the presence of 3 A molecular
2
the JPH coupling constants (Table 2).
sieves. The heterogeneous mixture was centrifuged, the organic
phase was separated, then evaporated to dryness, and dried under
vacuum.
Conclusion
N-(Benzylidene)decylimine (3a): Yield: 95% (yellow oil).[37]
Ϫ
1H
NMR (80.13 MHz, CDCl3): δ ϭ 8.26 (s, 1 H), 7.79Ϫ7.34 (m, 5
In conclusion, the diastereoselective, instantaneous, and
quantitative addition of spirophosphoranes 1؊2 to long-
chain imines, followed by selective one-pot hydrolysis of the
(α-aminoalkyl)spirophosphorane intermediates, provides a
3
H), 3.61 (t, JHH ϭ 6.5 Hz, 2 H), 1.71 (m, 2 H), 1.29 (m, 14 H),
3
0.89 (t, JHH ϭ 5.3 Hz, 3 H). Ϫ 13C NMR (62.90 MHz, CDCl3):
δ
ϭ
160.72 (s), 136.38 (s), 130.45Ϫ128.05 (m), 61.86 (s),
31.96Ϫ22.74 (m), 14.18 (s). Ϫ IR (KBr, cmϪ1): ν˜ ϭ 1647.7 (CϭN),
novel, direct, and efficient route for the nearly quantitative 1580.5 (CϭC). Ϫ MS (DCI/NH3); m/z: 246 (M ϩ 1)ϩ.
284
Eur. J. Org. Chem. 2000, 281Ϫ289

One-Pot Synthesis of New Polyfunctional Phosphorus Acid Amphiphiles
FULL PAPER
N-(Benzylidene)dodecylimine (3b): Yield: 91% (yellow oil).[38] Ϫ 1H
ive yields. In spite of their stability in solution under argon during
NMR (80.13 MHz, CDCl3): δ ϭ 8.26 (s, 1 H), 7.75Ϫ7.34 (m, 5 H), several days, all attempts to purify them failed due to their de-
3
3.61 (t, JHH ϭ 6.7 Hz, 2 H), 1.69 (m, 2 H), 1.26 (m, 18 H), 0.90
composition into tetracoordinated phosphorus compounds. In or-
(t, JHH ϭ 5.3 Hz, 3 H). Ϫ 13C NMR (62.90 MHz, CDCl3): δ ϭ der to characterize these PVϪC bond spirophosphoranes, the reac-
160.63 (s), 136.43 (s), 130.41Ϫ128.05 (m), 61.86 (s), 32.00Ϫ22.75 tion was then carried out directly in an NMR tube in deuterated
(m), 14.17 (s). Ϫ IR (KBr, cmϪ1): ν˜ ϭ 1645.9 (CϭN), 1579.7 (Cϭ solvent under argon. The imines 3a؊h (0.3 mmol) in CDCl3
3
C). Ϫ MS (DCI/NH3); m/z: 274 (M ϩ 1)ϩ.
(0.5 mL) were added to a solution of spirophosphorane 1؊2
(0.3 mmol) in CDCl3 (0.5 mL) at room temperature. (α-Aminoalk-
yl)spirophosphoranes 4a؊h and 5e were instantaneously and quan-
titatively formed and characterized by 31P, 1H, and 13C NMR
analysis.
1
N-(Benzylidene)tetradecylimine (3c): Yield: 93% (yellow oil). Ϫ H
NMR (250.13 MHz, CDCl3): δ ϭ 8.26 (s, 1 H), 7.76Ϫ7.38 (m, 5
3
H), 3.62 (t, JHH ϭ 7.0 Hz, 2 H), 1.72 (m, 2 H), 1.28 (m, 22 H),
3
0.91 (t, JHH ϭ 6.1 Hz, 3 H). Ϫ 13C NMR (62.90 MHz, CDCl3):
P-(α-Decylaminobenzyl)spirophosphorane
4a:
31P
NMR
δ ϭ 160.61 (s), 136.42 (s), 131.41 (s), 128.55 (s), 128.05 (s), 61.99
(s), 32.02Ϫ22.78 (m), 14.20 (s). Ϫ IR (KBr, cmϪ1): ν˜ ϭ 1647.6 (Cϭ
N), 1537.7 (CϭC). Ϫ MS (DCI/NH3); m/z: 302 (M ϩ 1)ϩ.
(81.01 MHz, CDCl3): δ ϭ Ϫ31.28 (d, 2JPH ϭ 25.2 Hz, 90%),
Ϫ32.63 (d, 2JPH ϭ 20.8 Hz, 10%). Ϫ 1H NMR (200.13 MHz,
2
CDCl3): δ ϭ 7.33 (m, 5 H), 4.55 (d, JHP ϭ 21.4 Hz, 1 H, 13%),
N-(Benzylidene)hexadecylimine (3d): Yield: 96%. Ϫ M.p. 27Ϫ28°C
4.38 (d, 2JHP ϭ 25.0 Hz, 1 H, 87%), 2.39 (m, 2 H), 1.58 (d, 3JHH ϭ
1
(pale yellow solid).[39] Ϫ H NMR (80.13 MHz, CDCl3): δ ϭ 8.26
2.3 Hz, 1 H, NH), 1.46 (s, 6 H), 1.34 (m, 2 H), 1.18 (m, 14 H), 1.05
3
(s, 1 H), 7.90Ϫ7.34 (m, 5 H), 3.60 (t, JHH ϭ 6.5 Hz, 2 H), 1.70
3
(s, 6 H), 0.83 (t, JHH ϭ 6.4 Hz, 3 H). Ϫ 13C NMR (50.32 MHz,
3
(m, 2 H), 1.26 (m, 26 H), 0.89 (t, JHH ϭ 5.3 Hz, 3 H). Ϫ 13C
CDCl3): δ ϭ 172.57 (s), 135.27 (s), 130.05Ϫ128.36 (m), 81.00 (s),
NMR (62.90 MHz, CDCl3): δ ϭ 160.67 (s), 136.42 (s),
130.42Ϫ128.04 (m), 61.86 (s), 31.98Ϫ22.74 (m), 14.16 (s). Ϫ IR
(KBr, cmϪ1): ν˜ ϭ 1647.2 (CϭN), 1580.5 (CϭC). Ϫ MS (DCI/
NH3); m/z: 330 (M ϩ 1)ϩ.
1
1
68.83 (d, JCP ϭ 180.0 Hz, minor isomer), 67.42 (d, JCP
ϭ
3
190.9 Hz, major isomer), 47.62 (d, JCP ϭ 24.3 Hz), 31.89Ϫ22.69
(m), 26.36 (s), 23.50 (s), 14.15 (s).
P-(α-Dodecylaminobenzyl)spirophosphorane
4b:
31P
NMR
N-(Benzylidene)octadecylimine (3e): Yield: 93%. Ϫ M.p. 34Ϫ36°C
1
(81.01 MHz, CDCl3): δ ϭ Ϫ31.48 (d, 2JPH ϭ 24.8 Hz, 90%);
(pale yellow solid).[40] Ϫ H NMR (80.13 MHz, CDCl3): δ ϭ 8.26
3
Ϫ32.82 (d, 2JPH ϭ 21.7 Hz, 10%). Ϫ 1H NMR (80.13 MHz,
CDCl3): δ ϭ 7.35Ϫ7.23 (m, 5 H), 4.38 (d, JHP ϭ 25.0 Hz, 1 H),
(s, 1 H), 7.69Ϫ7.34 (m, 5 H), 3.60 (t, JHH ϭ 6.7 Hz, 2 H), 1.69
2
3
(m, 2 H), 1.25 (m, 30 H), 0.88 (t, JHH ϭ 5.0 Hz, 3 H). Ϫ 13C
2.42 (m, 2 H), 1.47 (m, 7 H), 1.22 (m, 20 H), 1.07 (s, 6 H), 0.85
(m, 3 H). Ϫ 13C NMR (62.90 MHz, CDCl3): δ ϭ 172.40 (s), 135.27
(s), 129.22Ϫ127.93 (m), 80.88 (s), 69.49 (d, 1JCP ϭ 170.0 Hz, minor
isomer), 67.40 (d, 1JCP ϭ 190.4 Hz, major isomer), 47.56 (d, 3JCP ϭ
24.5 Hz), 31.83Ϫ22.62 (m), 27.02 (s), 23.33 (s), 14.15 (s).
NMR (62.90 MHz, CDCl3): δ ϭ 160.74 (s), 136.37 (s), 130.45 (s),
128.58 (s), 128.03 (s), 61.87 (s), 31.96Ϫ22.73 (m), 14.16 (s). Ϫ IR
(KBr, cmϪ1): ν˜ ϭ 1642.9 (CϭN), 1580.5 (CϭC). Ϫ MS (DCI/
NH3); m/z: 358 (M ϩ 1)ϩ.
N-(Benzylidene)oleylimine (3f): Yield: 96% (yellow oil). Ϫ 1H NMR
(250.13 MHz, CDCl3): δ ϭ 8.26 (s, 1 H), 7.76Ϫ7.38 (m, 5 H),
P-(α-Tetradecylaminobenzyl)spirophosphorane 4c: 31P NMR
(81.01 MHz, CDCl3): δ ϭ Ϫ31.39 (d, 2JPH ϭ 25.0 Hz, 95%);
Ϫ33.18 (d, 2JPH ϭ 19.9 Hz, 5%). Ϫ 1H NMR (80.13 MHz, CDCl3):
3
5.39Ϫ5.35 (m, 2 H), 3.62 (t, JHH ϭ 6.0 Hz, 2 H), 2.03 (m, 4 H),
1.72 (m, 2 H), 1.29 (m, 22 H), 0.91 (t, 3JHH ϭ 6.8 Hz, 3 H). Ϫ 13C
NMR (62.90 MHz, CDCl3): δ ϭ 160.60 (s), 136.43 (s),
130.40Ϫ128.05 (m), 61.83 (s), 32.67Ϫ22.62 (m), 14.16 (s). Ϫ IR
(KBr, cmϪ1): ν˜ ϭ 1647.0 (CϭN), 1579.6 (CϭC). Ϫ MS (DCI/
NH3); m/z: 356 (M ϩ 1)ϩ.
2
δ ϭ 7.34 (m, 5 H), 4.38 (d, JHP ϭ 24.8 Hz, 1 H), 2.41 (m, 2 H),
3
1.46 (s, 6 H), 1.20 (m, 25 H), 1.06 (s, 6 H), 0.84 (t, JHH ϭ 4.3 Hz,
3 H). Ϫ 13C NMR (50.32 MHz, CDCl3): δ ϭ 172.55 (s), 135.24 (s),
1
129.31Ϫ128.63 (m), 81.03 (s), 68.45 (d, JCP ϭ 188.7 Hz, minor
isomer), 67.35 (d, 1JCP ϭ 190.9 Hz, major isomer), 47.58 (d, 3JCP ϭ
24.2 Hz), 31.93Ϫ22.70 (m), 26.34 (s), 23.48 (s), 14.16 (s).
N-(Ethylidene)octadecylimine (3g): Yield: 86%. Ϫ M.p. 39Ϫ42°C
(orange solid). Ϫ 1H NMR (80.13 MHz, CDCl3): δ ϭ 7.65 (q,
3JHH ϭ 4.8 Hz, 1 H), 3.32 (t, 3JHH ϭ 5.9 Hz, 2 H), 1.91 (d, 3JHH ϭ
P-(α-Hexadecylaminobenzyl)spirophosphorane 4d: 31P NMR
2
3
(81.01 MHz, CDCl3): δ ϭ Ϫ31.28 (d, JPH ϭ 24.9 Hz, 90%);
4.7 Hz, 3 H), 1.24 (m, 32 H), 0.86 (t, JHH ϭ 5.1 Hz, 3 H). Ϫ
Ϫ33.63 (d, 2JPH ϭ 23.1 Hz, 10%). Ϫ 1H NMR (200.13 MHz,
13C NMR (50.32 MHz, CDCl3): δ ϭ 162.75 (s, minor product,syn),
160.31 (s, main product, anti), 61.70 (s, syn), 61.47 (s,anti),
31.99Ϫ22.76 (m), 22.24 (s, anti), 20.73 (s, syn), 14.19 (s). Ϫ IR
(KBr, cmϪ1): ν˜ ϭ 1673.2 (CϭN). Ϫ MS (DCI/NH3); m/z: 296 (M
ϩ 1)ϩ.
2
CDCl3): δ ϭ 7.40Ϫ7.32 (m, 5 H), 4.56 (d, JHP ϭ 21.0 Hz, 1 H,
2
15%), 4.39 (d, JHP ϭ 24.9 Hz, 1 H, 85%), 2.40 (m, 2 H), 1.48 (s,
3
6 H), 1.23 (m, 29 H), 1.07 (s, 6 H), 0.85 (t, JHH ϭ 6.7 Hz, 3 H).
Ϫ
13C NMR (50.32 MHz, CDCl3): δ ϭ 172.66 (s), 135.33 (s),
1
129.31Ϫ127.95 (m), 81.08 (s), 69.21 (d, JCP ϭ 184.5 Hz, minor
isomer), 67.44 (d, 1JCP ϭ 190.9 Hz, major isomer), 47.65 (d, 3JCP ϭ
24.2 Hz), 31.97Ϫ22.74 (m), 26.38 (s), 23.36 (s), 14.19 (s).
N-(Dodecylidene)octadecylimine (3h): Yield: 86% (pale yellow
solid). Ϫ 1H NMR (80.13 MHz, CDCl3): δ ϭ 8.50 (s, 1 H), 3.32 (t,
3JHH ϭ 6.6 Hz, 2 H), 1.50 (m, 2 H), 1.24 (m, 50 H), 0.86 (t, 3JHH ϭ
5.8 Hz, 6 H). Ϫ 13C NMR (50.32 MHz, CDCl3): δ ϭ 164.70 (s),
61.46 (s), 42.08Ϫ22.71 (m), 14.11 (s). Ϫ IR (KBr, cmϪ1): ν˜ ϭ 1666.7
(CϭN). Ϫ MS (DCI/NH3); m/z: 436 (M ϩ 1)ϩ.
P-(α-Octadecylaminobenzyl)spirophosphorane 4e: 31P NMR
(81.01 MHz, CDCl3): δ ϭ Ϫ31.37 (d, 2JPH ϭ 24.7 Hz, 80%);
Ϫ33.15 (d, 2JPH ϭ 18.2 Hz, 20%). Ϫ 1H NMR (80.13 MHz,
CDCl3): δ ϭ 7.36 (m, 5 H), 4.39 (d, 2JHP ϭ 24.8 Hz, 1 H), 2.43 (m,
General Procedure for the Synthesis of (α-Aminoalkyl)spirophospho-
ranes 4a؊h and 5e: The reaction was carried out under argon. The
imines 3a؊h (10 mmol) in anhydrous dichloromethane (10 mL)
were added dropwise to a stirred solution of spirophosphorane 1؊2
(10 mmol) in anhydrous dichloromethane (20 mL) at room tem-
perature. The progress of the reaction was monitored by 31P NMR
analysis. The addition reaction occurred instantaneously, and af-
forded (α-aminoalkyl)spirophosphoranes 4a؊h and 5e in quantitat-
3
2 H), 1.57 (m, 7 H), 1.22 (m, 32 H), 1.06 (s, 6 H), 0.84 (t, JHH
ϭ
6.6 Hz, 3 H). Ϫ 13C NMR (62.90 MHz, CDCl3): δ ϭ 172.51 (s),
135.21 (s), 129.24Ϫ128.62 (m), 80.99 (s), 68.91 (d, 1JCP ϭ 181.6 Hz,
minor isomer), 67.39 (d, 1JCP ϭ 190.9 Hz, major isomer), 47.58 (d,
3JCP ϭ 24.6 Hz), 31.90Ϫ22.67 (m), 26.23 (s), 23.45 (s), 14.10 (s).
P-(α-Oleylaminobenzyl)spirophosphorane
4f:
31P
NMR
(81.01 MHz, CDCl3): δ ϭ Ϫ31.31 (d, 2JPH ϭ 24.9 Hz, 75%);
Eur. J. Org. Chem. 2000, 281Ϫ289
285

´
K. Vercruysse, C. Dejugnat, A. Munoz, G. Etemad-Moghadam
FULL PAPER
Ϫ32.63 (d, 2JPH ϭ 21.1 Hz, 25%). Ϫ 1H NMR (250.13 MHz, (81.01 MHz, CD3COOD): δ ϭ 8.62 (d, 2JPH ϭ 16.8 Hz). Ϫ 1H
2
CDCl3): δ ϭ 7.38Ϫ7.33 (m, 5 H), 5.32 (m, 2 H), 4.55 (d, JHP
ϭ
NMR (250.13 MHz, CD3COOD): δ ϭ 7.59Ϫ7.42 (m, 5 H), 4.74
2
2
23.4 Hz, 1 H, 20%), 4.39 (d, JHP ϭ 24.9 Hz, 1 H, 80%), 2.40 (m, (d, JHP ϭ 17.9 Hz, 1 H), 2.94 (m, 2 H), 1.80 (m, 2 H), 1.63 (s, 3
3
2 H), 1.97 (m, 4 H), 1.47 (s, 6 H), 1.42 (s, 1 H),1.23 (m, 24 H), 1.07
H), 1.46 (s, 3 H), 1.29 (m, 19 H), 0.91 (t, JHH ϭ 6.6 Hz, 3 H).
(s, 6 H), 0.85 (t, JHH ϭ 6.8 Hz, 3 H). Ϫ 13C NMR (62.90 MHz,
Ϫ
13C NMR (62.90 MHz, CD3COOD): δ ϭ 179.19 (s), 130.99 (s),
3
CDCl3): δ ϭ 172.53 (s), 135.33 (s), 130.35Ϫ127.95 (m), 80.99 (s), 130.91Ϫ129.57 (m), 80.84 (s), 61.82 (d, 1JCP ϭ 146.3 Hz), 47.93 (s),
1
1
68.97 (d, JCP ϭ 181.1 Hz, minor isomer), 67.45 (d, JCP
ϭ
32.50Ϫ23.19 (m), 27.36 (s), 26.43 (s), 14.09 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3417.4 (broad, OH, NH), 2368.4 (PϪOH), 1724.7 (CϭO),
1632.2 (CϭC), 1168.3 (PϭO), 1067.2 (OϭPϪO). Ϫ MS (MNBA,
FAB > 0); m/z: 442 (M ϩ 1)ϩ. Ϫ C23H40NO5P (441.53): calcd. C
62.56, H 9.13, N 3.17; found C 62.56, H 9.48, N, 3.04.
3
190.9 Hz, major isomer), 47.60 (d, JCP ϭ 24.2 Hz), 32.60Ϫ22.55
(m), 26.32 (s), 23.46 (s), 14.11 (s).
P-(α-Octadecylaminoethyl)spirophosphorane
4g:
31P
NMR
3
(81.01 MHz, CDCl3): δ ϭ Ϫ25.90 (dq, 2JPH ϭ 23.8 Hz, JPH
ϭ
12.3 Hz, 65%); Ϫ26.20 (m, 35%). Ϫ 1H NMR (80.13 MHz,
CDCl3): δ ϭ 3.56Ϫ3.07 (m, 1 H), 2.65 (m, 2 H), 2.05 (m, 2 H), 1.58
Carboxyisobutyl α-Tetradecylaminobenzylphosphonic Acid Monoes-
ter (6c): Yield: 96%. Ϫ M.p. 166Ϫ167°C (from ethanol). Ϫ 31P
NMR (81.01 MHz, CD3COOD): δ ϭ 8.56 (d, 2JPH ϭ 16.4 Hz). Ϫ
1H NMR (250.13 MHz, CD3COOD): δ ϭ 7.57Ϫ7.42 (m, 5 H), 4.73
3
(m, 12 H), 1.55 (m, 3 H), 1.21 (m, 31 H), 0.83 (t, JHH ϭ 5.7 Hz,
3 H). Ϫ 13C NMR (50.32 MHz, CDCl3): δ ϭ 172.75 (s), 81.23 (s),
1
1
62.04 (d, JCP ϭ 183.9 Hz, minor isomer), 58.29 (d, JCP
ϭ
2
(d, JHP ϭ 17.8 Hz, 1 H), 2.97 (m, 2 H), 1.78 (m, 2 H), 1.62 (s, 3
194.2 Hz, major isomer), 48.64 (s), 32.69Ϫ22.70 (m), 26.33 (s),
3
H), 1.47 (s, 3 H), 1.29 (m, 23 H), 0.91 (t, JHH ϭ 5.7 Hz, 3 H).
24.16 (s), 16.12 (s), 14.14 (s).
Ϫ
13C NMR (62.90 MHz, CD3COOD): δ ϭ 179.53 (s), 131.03 (s),
P-(α-Octadecylaminododecyl)spirophosphorane 4h: 31P NMR
(81.01 MHz, CDCl3): δ ϭ Ϫ25.94 (d, 2JPH ϭ 24.8 Hz, 80%);
Ϫ29.74 (d, 2JPH ϭ 23.2 Hz, 20%). Ϫ 1H NMR (80.13 MHz,
CDCl3): δ ϭ 3.48Ϫ3.01 (m, 1 H), 2.65 (m, 2 H), 1.57 (m, 12 H),
130.17Ϫ129.56 (m), 81.43 (s), 61.70 (d, 1JCP ϭ 146.1 Hz), 47.89 (s),
32.52Ϫ23.20 (m), 27.51 (s), 26.48 (s), 14.10 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3430.2 (broad, OH, NH), 2362.6 (PϪOH), 1727.6 (CϭO),
1635.0 (CϭC), 1169.0 (PϭO), 1068.1 (OϭPϪO). Ϫ MS (MNBA,
FAB > 0); m/z: 470 (M ϩ 1)ϩ. Ϫ C25H44NO5P (469.58): calcd. C
63.94, H 9.44, N 2.81; found C 64.13, H 9.63, N 2.95.
1.22 (m, 43 H), 0.84 (t, JHH ϭ 5.4 Hz, 6 H). Ϫ 13C NMR
3
1
(50.32 MHz, CDCl3): δ ϭ 172.85 (s), 80.86 (s), 65.52 (d, JCP
ϭ
151.0 Hz, minor isomer), 63.75 (d, 1JCP ϭ 187.9 Hz, major isomer),
3
Carboxyisobutyl α-Hexadecylaminobenzylphosphonic Acid Monoes-
ter (6d): Yield: 88%. Ϫ M.p. 172Ϫ173°C (from ethanol). Ϫ 31P
NMR (81.01 MHz, CD3COOD): δ ϭ 8.62 (d, 2JPH ϭ 16.1 Hz). Ϫ
1H NMR (250.13 MHz, CD3COOD): δ ϭ 7.59Ϫ7.43 (m, 5 H), 4.74
49.63 (d, JCP ϭ 14.1 Hz), 34.44Ϫ22.72 (m), 26.24 (s), 24.09 (s),
14.15 (s).
P-(α-Octadecylaminobenzyl)spirophosphorane 5e: 31P NMR
(81.01 MHz, CDCl3): δ ϭ Ϫ29.65 (d, 2JPH ϭ 23.2 Hz, 85%);
Ϫ31.51 (d, 2JPH ϭ 21.5 Hz, 15%). Ϫ 1H NMR (200.13 MHz,
2
(d, JHP ϭ 17.6 Hz, 1 H), 2.96 (m, 2 H), 1.77 (m, 2 H), 1.63 (s, 3
3
H), 1.50 (s, 3 H), 1.31 (m, 27 H), 0.91 (t, JHH ϭ 6.6 Hz, 3 H).
2
CDCl3): δ ϭ 7.39Ϫ7.02 (m, 25 H), 4.49 (d, JHP ϭ 23.4 Hz, 1 H),
Ϫ
13C NMR (62.90 MHz, CD3COOD): δ ϭ 178.80 (s), 130.27 (s),
3
2.19 (m, 2 H), 1.77 (m, 2 H), 1.28 (m, 30 H), 0.90 (t, JHH
ϭ
1
129.83Ϫ129.56 (m), 81.1 (s), 61.60 (d, JCP ϭ 147.6 Hz), 47.92 (s),
32.52Ϫ23.21 (m), 27.53 (s), 26.83 (s), 14.14 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3422.2 (broad, OH, NH), 2359.4 (PϪOH), 1724.5 (CϭO),
1607.9 (CϭC), 1172.6 (PϭO), 1082.4 (OϭPϪO). Ϫ MS (Glycerol,
FAB > 0); m/z: 498 (M ϩ 1)ϩ. Ϫ C27H48NO5P (497.63): calcd. C
65.16, H 9.72, N 2.81; found C 65.35, H 9.88, N 2.83.
6.8 Hz, 3 H). Ϫ 13C NMR (50.32 MHz, CDCl3): δ ϭ 168.73 (s),
142.66Ϫ134.10 (m), 129.37Ϫ125.91 (m), 87.12 (s), 68.00 (d, 1JCP ϭ
181.2 Hz, minor isomer), 67.20 (d, 1JCP ϭ 189.5 Hz, major isomer),
3
48.34 (d, JCP ϭ 23.1 Hz), 32.01Ϫ22.78 (m), 14.23 (s).
General Procedure for the Synthesis of Carboxyalkyl (α-Aminoalkyl)-
phosphonic Acid Monoesters 6a؊h and 7e: Imine 3a؊h (10 mmol)
in anhydrous dichloromethane (10 mL) was added dropwise to a
stirred solution of spirophosphorane 1Ϫ2 (10 mmol) in anhydrous
dichloromethane (20 mL) at room temperature under argon. The
mixture was stirred for 5 min at room temperature and then con-
centrated to dryness. The residue was treated by acetonitrile/dis-
tilled water, 1:1 (50 mL). The precipitate, immediately formed after
addition, was collected by filtration, washed several times with
acetonitrile, recrystallized from ethanol, and then dried under vac-
uum to give a white powder.
Carboxyisobutyl α-Octadecylaminobenzylphosphonic Acid Monoes-
ter (6e): Yield: 90%. Ϫ M.p. 173Ϫ175°C (from ethanol). Ϫ 31P
NMR (81.01 MHz, CD3COOD): δ ϭ 8.67 (d, 2JPH ϭ 17.2 Hz). Ϫ
1H NMR (250.13 MHz, CD3COOD): δ ϭ 7.57Ϫ7.43 (m, 5 H), 4.70
2
(d, JHP ϭ 17.0 Hz, 1 H), 2.97 (m, 2 H), 1.78 (m, 2 H), 1.62 (m, 3
H), 1.49 (m, 3 H), 1.30 (m, 31 H), 0.91 (m, 3 H). Ϫ 13C NMR
(62.90 MHz,
CD3COOD):
δ ϭ 179.87 (s),
131.06 (s),
130.25Ϫ129.57 (m), 80.97 (s), 61.79 (d, 1JCP ϭ 145.7 Hz), 47.81 (s),
32.55Ϫ23.23 (m), 27.52 (s), 26.50 (s), 14.16 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3440.7 (broad, OH, NH), 1727.1 (CϭO), 1635.9 (CϭC), 1169.8
(PϭO), 1068.2 (OϭPϪO). Ϫ MS (MNBA, FAB > 0); m/z: 526 (M
ϩ 1)ϩ. Ϫ C29H52NO5P (525.68): calcd. C 66.26, H 9.97, N 2.66;
found C 66.12, H 10.25, N 2.64.
Carboxyisobutyl α-Decylaminobenzylphosphonic Acid Monoester
(6a): Yield: 87%. Ϫ M.p. 173Ϫ174°C (from ethanol); 31P NMR
(81.01 MHz, CD3COOD): δ ϭ 8.60 (d, 2JPH ϭ 17.5 Hz). Ϫ 1H
NMR (250.13 MHz, CD3COOD): δ ϭ 7.60Ϫ7.43 (m, 5 H), 4.71
2
(d, JHP ϭ 17.8 Hz, 1 H), 2.96 (m, 2 H), 1.79 (m, 2 H), 1.64 (s, 3
Carboxyisobutyl α-Oleylaminobenzylphosphonic Acid Monoester
(6f): Yield: 91%. Ϫ M.p. 169Ϫ171°C (from ethanol). Ϫ 31P NMR
3
H), 1.58 (s, 3 H), 1.29 (m, 15 H), 0.91 (t, JHH ϭ 6.2 Hz, 3 H).
Ϫ
13C NMR (62.90 MHz, CD3COOD): δ ϭ 179.71 (s), 131.13 (s),
(81.01 MHz, CDCl3): δ ϭ 8.64 (m). Ϫ 1H NMR (250.13 MHz,
130.29Ϫ129.59 (m), 81.29 (s), 61.60 (d, 1JCP ϭ 146.2 Hz), 47.86 (s),
32.48Ϫ23.20 (m), 27.65 (s), 26.72 (s), 14.16 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3433.3 (broad, OH, NH), 2529.3 (PϪOH), 1725.0 (CϭO),
1637.3 (CϭC), 1192.3 (PϭO), 1073.7 (OϭPϪO). Ϫ MS (Glycerol,
FAB > 0); m/z: 414 (M ϩ 1)ϩ. Ϫ C21H36NO5P (413.47): calcd. C
61.00, H 8.78, N 3.39; found C 60.96, H 8.79, N 3.32.
2
CDCl3): δ ϭ 7.59Ϫ7.43 (m, 5 H), 5.37 (m, 2 H), 4.67 (d, JHP
ϭ
17.0 Hz, 1 H), 2.98 (m, 2 H), 2.05 (m, 4 H), 1.76 (m, 2 H), 1.62 (s,
3
3 H), 1.52 (s, 3 H), 1.30 (m, 25 H), 0.91 (t, JHH ϭ 6.8 Hz, 3 H).
Ϫ
13C NMR (62.90 MHz, CDCl3): δ ϭ 172.00 (s), 130.60 (s),
130.55Ϫ129.60 (m), 81.33 (s), 61.80 (d, 1JCP ϭ 147.2 Hz), 47.00 (s),
33.12Ϫ23.22 (m), 27.64 (s), 26.00 (s), 14.17 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3418.6 (broad, OH, NH), 2362.8 (PϪOH), 1726.4 (CϭO),
1635.8 (CϭC), 1169.6 (PϭO), 1068.5 (OϭPϪO). Ϫ MS (Glycerol,
Carboxyisobutyl α-Dodecylaminobenzylphosphonic Acid Monoester
(6b): Yield: 74%. Ϫ M.p. 173Ϫ175°C (from ethanol). Ϫ 31P NMR
286
Eur. J. Org. Chem. 2000, 281Ϫ289

One-Pot Synthesis of New Polyfunctional Phosphorus Acid Amphiphiles
FULL PAPER
FAB > 0); m/z: 524 (M ϩ 1)ϩ. Ϫ C29H50NO5P (523.67): calcd C (200.13 MHz, CD3COOD): δ ϭ 7.53Ϫ7.41 (m, 5 H), 4.64 (d,
66.51, H 9.62, N 2.67; found C 66.79, H 9.33, N 2.64.
2JHP ϭ 17.2 Hz, 1 H), 2.94 (m, 2 H), 1.79 (m, 2 H), 1.28 (m, 15
3
H), 0.90 (t, JHH ϭ 6.7 Hz, 3 H). Ϫ 13C NMR (50.32 MHz,
Carboxyisobutyl α-Octadecylaminoethylphosphonic Acid Monoester
(6g): Yield: 80%. Ϫ M.p. 139Ϫ140°C (from ethanol). Ϫ 31P NMR
1
CD3COOD): δ ϭ 131.09 (s), 131.00Ϫ129.74 (m), 61.81 (d, JCP
ϭ
136.8 Hz), 48.10 (s), 32.58Ϫ23.31 (m), 14.23 (s); IR (KBr, cmϪ1):
ν˜ ϭ 3404.8 (broad, OH, NH), 2288.0 (PϪOH), 1608.3 (CϭC),
1173.1 (PϭO), 1082.6 (OϭPϪO). Ϫ MS (DCI/NH3); m/z: 328 (M
ϩ 1)ϩ. Ϫ C17H30NO3P (327.39): calcd. C 62.37, H 9.24, N 4.28;
found C 61.81, H 9.31, N 4.11.
(81.01 MHz, CDCl3): δ ϭ 11.96 (dd, 2JPH
ϭ
3JPH ϭ 14.8 Hz). Ϫ
1H NMR (250.13 MHz, CDCl3): δ ϭ 9.99 (m, 1 H), 7.88 (m, 1 H),
3.29 (m, 1 H), 2.85 (m, 2 H), 1.75 (m, 2 H), 1.66 (s, 3 H), 1.48 (s,
3 H), 1.45 (m, 3JHH ϭ 7.1 Hz, 3 H), 1.23 (m, 31 H), 0.86 (t, 3JHH ϭ
6.4 Hz, 3 H). Ϫ 13C NMR (62.90 MHz, CDCl3): δ ϭ 178.11 (s),
1
78.78 (s), 51.60 (d, JCP ϭ 151.0 Hz), 46.30 (s), 31.98Ϫ22.75 (m), (α-Dodecylaminobenzyl)phosphonic Acid (8b): Yield: 83%. Ϫ M.p.
28.30 (s), 26.60 (s), 14.18 (s), 11.33 (d, 2JCP ϭ 7.0 Hz). Ϫ IR (KBr,
cmϪ1): ν˜ ϭ 3422.2 (broad, OH, NH), 2503.9 (PϪOH), 1731.6 (Cϭ
225Ϫ227°C (from butanol).
CD3COOD): δ ϭ 12.05 (d, JPH
Ϫ
31P NMR (81.01 MHz,
16.7 Hz).
1H NMR
2
ϭ
Ϫ
O), 1180.5 (PϭO), 1060.0 (OϭPϪO). Ϫ MS (DCI/NH3); m/z: 464 (250.13 MHz, CD3COOD): δ ϭ 7.56Ϫ7.42 (m, 5 H), 4.66 (d,
(M ϩ 1)ϩ. Ϫ C24H50NO5P (463.62): calcd C 62.17, H 10.87, N
3.02; found C 62.09, H 10.83, N 3.00.
2JHP ϭ 17.4 Hz, 1 H), 2.95 (m, 2 H), 1.79 (m, 2 H), 1.29 (m, 19
3
H), 0.91 (t, JHH ϭ 6.1 Hz, 3 H). Ϫ 13C NMR (62.90 MHz,
1
CD3COOD): δ ϭ 130.84 (s), 130.77Ϫ129.66 (m), 61.70 (d, JCP
ϭ
Carboxyisobutyl α-Octadecylaminododecylphosphonic Acid Mono-
ester (6h): Yield: 93%. Ϫ M.p. 147Ϫ150°C (from dichloromethane).
137.4 Hz), 47.94 (s), 32.51Ϫ23.20 (m), 14.10 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3495.4 (broad, OH, NH), 2367.5 (PϪOH), 1608.3 (CϭC),
1172.3 (PϭO), 1082.6 (OϭPϪO). Ϫ MS (MNBA, FAB > 0); m/z:
356 (M ϩ 1)ϩ. Ϫ C19H34NO3P (355.44): calcd. C 64.18, H 9.64, N
3.94; found C 63.40, H 9.72, N 3.79.
Ϫ
31P NMR (81.01 MHz, CDCl3 and two drops of CD3COOD):
2
3
1
δ ϭ 9.46 (dt, JPH ϭ JPH ϭ 16.0 Hz). Ϫ H NMR (250.13 MHz,
CDCl3 and two drops of CD3COOD): δ ϭ 3.10 (m, 1 H), 2.76 (m,
3
2 H), 1.70 (m, 5 H), 1.48 (s, 3 H), 1.25 (m, 51 H), 0.88 (t, JHH
ϭ
6.6 Hz, 6 H). Ϫ 13C NMR (50.32 MHz, CDCl3 and two drops of
(α-Tetradecylaminobenzyl)phosphonic Acid (8c): Yield: 67%. Ϫ M.p.
CD3COOD): δ ϭ 178.76 (s), 79.82 (s), 56.10 (d, JCP ϭ 147.8 Hz), 213Ϫ216°C. Ϫ 31P NMR (81.01 MHz, CD3COOD): δ ϭ 10.90
1
47.08 (s), 31.94Ϫ22.71 (m), 27.86 (s), 14.11 (s). Ϫ IR (KBr, cmϪ1): (m). Ϫ H NMR (250.13 MHz, CD3COOD): δ ϭ 7.55Ϫ7.41 (m, 5
1
ν˜ ϭ 3480.7 (broad, OH, NH), 2500.5 (PϪOH), 1720.4 (CϭO), H), 4.54 (d, 2JHP ϭ 17.2 Hz, 1 H), 2.94 (m, 2 H), 1.76 (m, 2 H), 1.30
1177.0 (PϭO), 1066.8 (OϭPϪO). Ϫ MS (Glycerol, FAB > 0); m/
(m, 23 H), 0.91 (t, 3JHH ϭ 6.4 Hz, 3 H). Ϫ 13C NMR (62.90 MHz,
z: 604 (M ϩ 1)ϩ. Ϫ C34H70NO5P (603.88): calcd. C 67.62, H 11.68, CD3COOD): δ ϭ 130.78 (s), 130.03Ϫ129.54 (m), 61.85 (d, JCP
ϭ
1
N 2.32; found C 67.33, H 11.62, N 2.29.
137.1 Hz), 47.86 (s), 32.52Ϫ23.21 (m), 14.12 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3395.4 (broad, OH, NH), 2317.8 (PϪOH), 1609.1 (CϭC),
1173.5 (PϭO), 1082.8 (OϭPϪO). Ϫ MS (Glycerol, FAB >0); m/z:
384 (M ϩ 1)ϩ. Ϫ C21H38NO3P (383.49): calcd. C 65.77, H 9.99, N
3.65; found C 65.78, H 10.16, N 3.60.
Carboxybenzil α-Octadecylaminobenzylphosphonic Acid Monoester
(7e): Yield: 78%. Ϫ M.p. 125Ϫ128°C (from diethyl ether). Ϫ 31P
NMR (81.01 MHz, CDCl3): δ ϭ 7.62 (m).
(80.13 MHz, CDCl3): δ ϭ 7.51Ϫ7.28 (m, 15 H), 4.30 (d, JHP
Ϫ
1H NMR
2
ϭ
16.8 Hz, 1 H), 2.50 (m, 2 H), 1.86 (m, 3 H), 1.30 (m, 30 H), 0.93 (α-Hexadecylaminobenzyl)phosphonic Acid (8d): Yield: 80%. Ϫ
3
(t, JHH ϭ 6.4 Hz, 3 H). Ϫ 13C NMR (50.32 MHz, CDCl3): δ ϭ
M.p. 214Ϫ216°C (from butanol). Ϫ 31P NMR (81.01 MHz,
176.92 (s), 142.96Ϫ130.11 (m), 129.32Ϫ127.60 (m), 86.68 (s), 60.78 CD3COOD): δ ϭ 12.11 (d, JPH ϭ 17.2 Hz, 1 H). Ϫ 1H NMR
2
1
(d, JCP ϭ 138.8 Hz), 48.38 (s), 31.96Ϫ22.72 (m), 14.11 (s). Ϫ IR (250.13 MHz, CD3COOD): δ ϭ 7.55Ϫ7.41 (m, 5 H), 4.65 (d,
(KBr, cmϪ1): ν˜ ϭ 3411.1 (broad, OH, NH), 2464.2 (PϪOH), 1711.5
(CϭO), 1601.4 (CϭC), 1172.6 (PϭO), 1071.4 (OϭPϪO). Ϫ MS
(DCI/NH3); m/z: 649 (M)ϩ.
2JHP ϭ 17.3 Hz, 1 H), 2.94 (m, 2 H), 1.79 (m, 2 H), 1.30 (m, 27
3
H), 0.91 (t, JHH ϭ 6.7 Hz, 3 H). Ϫ 13C NMR (62.90 MHz,
1
CD3COOD): δ ϭ 130.83 (s), 130.75Ϫ129.65 (m), 61.70 (d, JCP
ϭ
137.7 Hz), 48.05 (s), 32.52Ϫ23.20 (m), 14.09 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3430.4 (broad, OH, NH), 2359.4 (PϪOH), 1607.9 (CϭC),
1172.6 (PϭO), 1082.4 (OϭPϪO). Ϫ MS (MNBA, FAB > 0); m/z:
412 (M ϩ 1)ϩ. Ϫ C23H42NO3P (411.54): calcd. C 67.12, H 10.29,
N 3.40; found C 67.20, H 10.47, N 3.38.
General Procedure for the Synthesis of (α-Aminoalkyl)phosphonic
Acids 8a؊h: Their synthesis can be accomplished either by acid
hydrolysis of (α-aminoalkyl)phosphonocarboxylic acids 6a؊h and
7e (Method A), or by one-pot acid hydrolysis of the reaction mix-
ture (Method B). Ϫ Method A: (α-Aminoalkyl)phosphonocarbox-
ylic acids 6a؊h and 7e (1.1 mmol) in 20% aqueous hydrochloric (α-Octadecylaminobenzyl)phosphonic Acid (8e): Yield: 78%. Ϫ M.p.
acid (7 mL) were heated under reflux for 5Ϫ10 h. The progress of
the reaction was monitored by 31P NMR analysis. The mixture
was then allowed to cool to room temperature. The mixture was
concentrated under vacuum. The precipitate was collected by fil-
215Ϫ217°C (from 2-propanol).
CD3COOD): δ ϭ 10.98 (m).
CD3COOD): δ ϭ 7.54Ϫ7.40 (m, 5 H), 4.55 (d, JHP ϭ 17.0 Hz, 1
Ϫ
31P NMR (81.01 MHz,
Ϫ
1H NMR (250.13 MHz,
2
3
H), 2.92 (m, 2 H), 1.76 (m, 2 H), 1.31 (m, 31 H), 0.91 (t, JHH
ϭ
tration and washed several times with distilled water, methanol, and 6.6 Hz, 3 H). Ϫ 13C NMR (50.32 MHz, CDCl3 and two drops of
1
diethyl ether. The white solid was recrystallized from ethanol, 2-
propanol, or butanol if necessary, then dried under vacuum. Ϫ
Method B: The reaction mixture obtained from spirophosphorane
1؊2 (3.9 mmol) and imine 3a؊h (3.9 mmol), in anhydrous di-
chloromethane (20 mL) at room temperature under stirring for
5Ϫ10 min, was concentrated in vacuo. To the residue was added
20% aqueous hydrochloric acid (25 mL), with stirring; the mixture
was heated under reflux for 5Ϫ10 h. After cooling to room tem-
perature, the mixture was worked up as described for Method A.
CD3COOD): δ ϭ 131.50 (s), 128.96Ϫ128.76 (m), 61.72 (d, JCP
ϭ
137.6 Hz), 47.30 (s), 31.92Ϫ22.68 (m), 14.07 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3422.5 (broad, OH, NH), 2364.7 (PϪOH), 1606.8 (CϭC),
1169.8 (PϭO), 1069.1 (OϭPϪO). Ϫ MS (DCI/NH3); m/z: 440 (M
ϩ 1)ϩ. Ϫ C25H46NO3P (439.60): calcd. C 68.30, H 10.55, N 3.19;
found C 68.61, H 10.24, N 2.99.
(α-Oleylaminobenzyl)phosphonic Acid (8f): Yield: 66%. Ϫ M.p.
212Ϫ214°C (from ethanol). Ϫ 31P NMR (81.01 MHz, CDCl3 and
two drops of CD3COOD): δ ϭ 10.06 (d, JPH ϭ 15.7 Hz). Ϫ 1H
2
(α-Decylaminobenzyl)phosphonic Acid (8a): Yield: 92%. Ϫ M.p.
NMR (80.13 MHz, CDCl3 and two drops of CD3COOD): δ ϭ 7.29
2
214Ϫ216°C (from ethanol).
Ϫ
31P NMR (81.01 MHz, (m, 5 H), 5.23 (m, 2 H), 4.32 (d, JHP ϭ 17.0 Hz, 1 H), 2.65 (m, 2
2
3
CD3COOD): δ ϭ 11.79 (d, JPH
ϭ
16.3 Hz).
Ϫ
1H NMR H), 1.91 (m, 4 H), 1.57 (m, 2 H), 1.16 (m, 23 H), 0.77 (t, JHH
ϭ
Eur. J. Org. Chem. 2000, 281Ϫ289
287

´
K. Vercruysse, C. Dejugnat, A. Munoz, G. Etemad-Moghadam
FULL PAPER
5.2 Hz, 3 H). Ϫ 13C NMR (50.32 MHz, CDCl3 and two drops of
[12] [12a]
I. M. Lefebvre, S. A. Evans, Jr., J. Org. Chem. 1997, 62,
[12b]
7532Ϫ7533. Ϫ
C. K. McClure, P. K. Mishra, C. W. Grote,
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T. Gharbaoui, M. Chiadmi, A. Tomas, J. Royer, H.-P. Husson,
Tetrahedron 1997, 53, 3627Ϫ3636.
1
CD3COOD): δ ϭ 131.08 (s), 130.66Ϫ129.82 (m), 61.74 (d, JCP
ϭ
137.0 Hz), 48.01 (s), 33.21Ϫ23.33 (m), 14.29 (s). Ϫ IR (KBr, cmϪ1):
ν˜ ϭ 3392.9 (broad, OH, NH), 2323.8 (PϪOH), 1609.5 (CϭC),
1173.3 (PϭO), 1080.9 (OϭPϪO). Ϫ MS (DCI/NH3); m/z: 438 (M
ϩ 1)ϩ. Ϫ C25H44NO3P (437.58): calcd. C 68.62, H 10.14, N 3.20;
found C 68.69, H 10.18, N 3.09.
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[14] [14a]
(α-Octadecylaminoethyl)phosphonic Acid (8g): Yield: 79%. Ϫ 190°C
(decomposition). Ϫ 31P NMR (81.01 MHz, CD3COOD): δ ϭ 15.30
(m). Ϫ 1H NMR (200.13 MHz, CD3COOD): δ ϭ 3.49 (m, 1 H),
3.17 (m, 2 H), 1.78 (m, 2 H), 1.32 (m, 33 H), 0.91 (t, 3JHH ϭ 6.3 Hz,
3 H). Ϫ 13C NMR (50.32 MHz, CD3COOD): δ ϭ 52.90 (d, 1JCP ϭ
141.5 Hz), 47.17 (s), 32.67Ϫ23.36 (m), 14.27 (s), 11.50 (s). Ϫ IR
(KBr, cmϪ1): ν˜ ϭ 3422.2 (broad, OH, NH), 1173.3 (PϭO), 1080.7
(OϭPϪO). Ϫ MS (DCI/NH3); m/z: 378 (M ϩ 1)ϩ. Ϫ C20H44NO3P
(377.53): calcd. C 63.63, H 11.75, N 3.71; found C 63.39, H 12.19,
N 3.61.
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S. W. A. Bligh, C. M. McGrath, S. Failla, P. Finocchiaro,
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1179.2 (PϭO), 1078.2 (OϭPϪO). Ϫ MS (DCI/NH3); m/z: 518 (M
ϩ 1)ϩ. Ϫ C30H64NO3P (517.79): calcd. C 69.59, H 12.46, N 2.70;
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Eur. J. Org. Chem. 2000, 281Ϫ289

One-Pot Synthesis of New Polyfunctional Phosphorus Acid Amphiphiles
FULL PAPER
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