Carbanionic displacement reactions at phosphorus. Part III.1 Cyanomethylphosphonate vs. cyanomethylenediphosphonate. Synthesis and solid-state structures

Article abstract of DOI:10.1039/b003371p

The results of the carbanionic reaction between acetonitrile and chlorophosphates depend strongly on the nature of the metallating agent (LiTMP, LDA, LiHMDS). According to the nature of the base, the reaction can be directed towards the formation of either cyanomethylphosphonates 3 or cyanomethylenediphosphonates 5. Electrophilic halogenation of lithiated cyanomethylphosphonate 2a leads to the mono-chloro 17, -bromo 18 and -iodo 19 derivatives. Only the monochloro product 17 is stable enough to be isolated in pure form. The structures of cyanobenzylphosphonate 10b, cyanomethylenediphosphonate 5b and its corresponding lithiated carbanion 4b are determined by X-ray crystallography. The polymeric structure, coupled with a wide charge delocalization, without C-Li contacts, is in agreement with the lack of reactivity towards electrophiles. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/b003371p

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Carbanionic displacement reactions at phosphorus. Part III.1
Cyanomethylphosphonate vs. cyanomethylenediphosphonate.
Synthesis and solid-state structures
1
Bogdan Iorga, Louis Ricard and Philippe Savignac
Laboratoire Hétéroéléments et Coordination, UMR CNRS 7653, DCPH, Ecole Polytechnique,
91128 Palaiseau Cedex, France. Fax: ϩ33 1 69 33 39 90;
E-mail: savignac@poly.polytechnique.fr
Received (in Cambridge, UK) 26th April 2000, Accepted 10th August 2000
First published as an Advance Article on the web 12th September 2000
The results of the carbanionic reaction between acetonitrile and chlorophosphates depend strongly on the nature
of the metallating agent (LiTMP, LDA, LiHMDS). According to the nature of the base, the reaction can be directed
towards the formation of either cyanomethylphosphonates 3 or cyanomethylenediphosphonates 5. Electrophilic
halogenation of lithiated cyanomethylphosphonate 2a leads to the mono-chloro 17, -bromo 18 and -iodo 19
derivatives. Only the monochloro product 17 is stable enough to be isolated in pure form. The structures of
cyanobenzylphosphonate 10b, cyanomethylenediphosphonate 5b and its corresponding lithiated carbanion 4b
are determined by X-ray crystallography. The polymeric structure, coupled with a wide charge delocalization,
without C–Li contacts, is in agreement with the lack of reactivity towards electrophiles.
All subsequent anionic preparations of diethyl cyanomethyl-
Introduction
phosphonate 3a reported in the literature utilize LDA† (2 eq.) for
Dialkyl cyanoalkylphosphonates are well known reagents for
metallation of acetonitrile, but the yields are not so high and
the two-carbon-chain elongation of aldehydes and ketones to
never exceed 53%.23,24 Recently, our interest in the synthesis of
α,β-unsaturated nitriles via the Horner–Wadsworth–Emmons
α-monohalogenated cyanomethylphosphonates prompted us to
(H–W–E) reaction.2 In the past, diethyl cyanomethyl-
phosphonate 3a played an important role in the elucidation of
reexamine the formation of 1-cyanoalkylphosphonates by
nucleophilic substitution at phosphorus. We should like to add
the mechanism of this reaction.3 In addition to the method-
some useful improvements to this often quoted procedure
ology for the olefination of carbonyl compounds, there are a
recommended by several investigators.16–22
number of other important and useful synthetic procedures
allowing the conversion of the cyano group into amino,4,5
amido6 and carboxy7,8 groups with conservation of the
phosphoryl group.
Results and discussion
By monitoring (31P NMR) the reaction of diethyl chloro-
phosphate 1a with lithiated acetonitrile generated at low tem-
perature with LDA (2 eq.), we identified in the reaction mixture
two products attributed to the anions of diethyl cyanomethyl-
phosphononate 2a [δP(THF) ϩ43 ppm] and tetraethyl
cyanomethylenediphosphonate 4a [δP(THF) ϩ33 ppm] in a
65:35 ratio (Scheme 1). The same reaction mixture, in a slightly
different ratio, was obtained using the couple LDA (1 eq.)–
n-BuLi (1 eq.) or LiTMP† (2 eq.) as metallating agent
(Table 1). These results are not dependent on the nature of the
Two main routes are known for the synthesis of dialkyl
cyanoalkylphosphonates. In the first one, the thermal route or
Michaelis–Arbuzov reaction,9,10 the phosphorus substrate acts
as nucleophile while in the second, the carbanionic route,11
the phosphorus substrate acts as electrophile. Generally, the
thermal route is limited to the synthesis of dialkyl cyano-
methylphosphonates7,12,13 and tolerates only a methyl group on
the α-carbon atom to phosphorus.14,15 For example, diethyl
cyanomethylphosphonate 3a was produced in 90% yield on
heating triethyl phosphite and chloroacetonitrile,15 while the
formation of diethyl 1-cyanoethylphosphonate 11a from
2-bromopropionitrile resulted in only 55% yield after a 24 h
reflux.15 By contrast, the carbanionic route, described for the
first time in 1975,4 is more versatile and possesses significant
synthetic advantages.11 Cyanomethylphosphonates as well as
other 1-cyanoalkylphosphonates can be easily prepared in good
yields by treatment, at low temperature, of the corresponding
lithiated nitriles with chlorophosphates.4,5 Thus, the addition of
bis(dimethylamino)phosphorochloridate (1 eq.) at low tem-
perature to lithiated acetonitrile (2 eq.) at Ϫ78 ЊC provides the
desired cyanomethylphosphonate in 95% yield.4 An added
advantage of the carbanionic route is that the lithiated inter-
mediate generated in situ can be directly employed in a
subsequent reaction.16–22 Moreover, ester appendages at phos-
phorus are easily suited to the reaction conditions. The only
inconvenience of this approach is the loss of one half of the
starting acetonitrile, unacceptable for homologous nitriles and
for large-scale syntheses.
Scheme 1 Reagents and conditions: i, LiHMDS (2 eq.), THF, Ϫ78 ЊC;
ii, LDA (2 eq.), THF, Ϫ78 ЊC; iii, 3 M HCl, 0 ЊC.
† Abbreviations. LDA, lithium diisopropylamide. LiTMP, lithium
2,2,6,6-tetramethylpiperidide. LiHMDS, lithium hexamethyldisilazide.
DME, 1,2-dimethoxyethane. TMSCl, trimethylsilyl chloride. NFBS,
N-fluorobenzenesulfonimide.
DOI: 10.1039/b003371p
J. Chem. Soc., Perkin Trans. 1, 2000, 3311–3316
This journal is © The Royal Society of Chemistry 2000
3311

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Table 1
Base
phosphonates 7a–9a upon treatment with 1a. After work-up,
excellent yields of diethyl cyanoalkylphosphonates 11a–13a are
obtained (Table 2, entries 11a–13a).
Solvent
2 (%)
4 (%)
Extension of the electrophilic phosphorylation to nitriles
bearing functional groups (RЈ = MeO, Me2N, F, Cl) was dis-
appointing. As already observed by Dinizo et al.25 and con-
firmed later,24 even with an excess of chlorophosphate under
internal quench conditions the metallation of nitriles is fol-
lowed by self-condensation to afford the β-aminoacrylonitrile
derivatives. Variation of base (LiHMDS, LDA, PriMgCl) or
changes in reagents’ addition order were totally ineffective. We
found that in the best reaction conditions, by slow addition, at
low temperature, of nitrile to the mixture of chlorophosphate
and LiHMDS, the methoxy-, dimethylamino-, fluoro-, and
chloroacetonitriles gave similar results and only 30% (determin-
ated by 31P NMR) of the expected cyanoalkylphosphonates was
formed. However, a general method for the preparation
of fluoroalkenes by phosphorylation of lithiated fluoro-
acetonitrile followed by condensation on aromatic aldehydes
was reported by Patrick and Nadji in 1990.26 There are a few
more examples of alkylation reactions of lithiated methoxy-
and dimethylaminoacetonitrile, but these results seem not to
be reproducible.27,28
In connection with our recent work on the selective electro-
philic halogenation of α-phosphorylated carbanions protected
by a trimethylsilyl group,29–31 it became obvious that the use
of silylated phosphononitriles could offer an entry into
the α-monohalogenated phosphononitriles. For this purpose,
diethyl 1-lithio(cyano)methylphosphonate 2a was treated with
TMSCl† to give cleanly and quantitatively diethyl 1-lithio-1-
(trimethylsilyl)(cyano)methylphosphonate [δP(THF) ϩ43.6].
However, this method appears to be ineffective since this
carbanion was completely inert towards electrophilic halogen-
ation reagents. Moreover, it readily underwent desilylation on
acidic work-up.
2 LDA
2 LiTMP
1 n-BuLi ϩ 1 LDA
2 LiHMDS
2 LiHMDS ϩ 2 LiBr
2 LiHMDS
THF
THF
THF
THF
THF
DME
65
70
75
100
100
100
35
30
25
0
0
0
Table 2
δP(CLi)
(ppm)a
δP(CH)
Yield
(%)
Entry
RЈ
(ppm)b
Base
3a
10a
11a
12a
13a
H
44.7
36.3
45.2
45.9
44.8
15.2
15.0
20.4
18.6
18.7
LiHMDS
LiHMDS
LDA
LDA
LDA
88
99
89
98
99
Ph
Me
Et
Pr
a In THF. b In CDCl3.
phosphoryl group, since 2-chloro-5,5-dimethyl-2-oxo-1,3,2-
dioxaphosphorinane 1b shows comparable behaviour. In
marked contrast, the use of LiHMDS† (2 eq.) suppresses com-
pletely the formation of the diphosphonate anions 4 and orien-
tates the reaction towards the phosphonate anions 2. These are
quantitatively generated as the sole products and after acidic
work-up the cyanomethylphosphonates 3 are isolated in pure
form and excellent yield (Scheme 1, Table 2). In a similar way,
the cyanomethylenediphosphonates 5 are cleanly obtained by
using LDA, chlorophosphate and acetonitrile in the proportions
3:2:1. Presumably, in the presence of a coordinating base such
as diisopropylamine, anions 2 are less aggregated and thus more
reactive toward chlorophosphate 1. In contrast, hexamethyl-
disilazane, a less coordinating base, does not prevent the aggre-
gation of anions 2, which become less reactive. The addition of
salt (LiBr, 2 eq.) or the replacement of THF by DME† does not
change the reaction path and 2 remains the only species formed
(Table 1). Consequently, by proper choice of the metallating
agent we are able to orientate the reaction between chlorophos-
phates 1 and acetonitrile towards the preparation of either
exclusively the cyanomethylphosphonate 3 or mixtures contain-
ing substantial amounts of the cyanomethylenediphosphonate
5 (Scheme 1).
The relative inertness of diethyl lithio(trimethylsilyl)(cyano)-
methylphosphonate being due to the trimethylsilyl group, we
repeated the halogenation reaction without the protecting
group, according to Scheme 3. The unprotected carbanion 2a
With these new results in hand, a general and reproducible
procedure for the preparation of diethyl cyanomethyl-
phosphonate 3a, α-aryl- 10a and α-alkyl-substituted 11a–13a
cyanomethylphosphonates by electrophilic phosphorylation of
lithiated nitriles has been developed (Scheme 2). As for
Scheme 3 Reagents and conditions: i, LiHMDS (2 eq.), THF, Ϫ78 ЊC;
ii, C2Cl6, C2Cl4Br2 or I2, Ϫ78 ЊC; iii, 3 M HCl, 0 ЊC.
readily undergoes halogenation with chlorination (C2Cl6),
bromination (C2Cl4Br2) and iodination (I2) reagents to give
exclusively the halogenated cyanomethylphosphonate carb-
anions 14–16 [δP(THF) 29–33 ppm]. On acidic treatment, only
diethyl 1-cyano(chloro)methylphosphonate 17 was sufficiently
stable to be isolated, while the bromo derivative 18 decomposed
slowly at room temperature. By contrast, the iodo derivative 19
decomposed by losing the halogen during the work-up and only
the 31P NMR spectrum could be recorded.
Scheme 2 Reagents and conditions: i, base (2 eq.), THF, Ϫ78 ЊC; ii,
3 M HCl.
In spite of the previously reported32 results on electrophilic
fluorination of 3a, we were unable to obtain the desired
1-cyano(fluoro)methylphosphonate by fluorination of 3a using
NFBS.† Under our conditions, a single fluorinated product was
detected as a singlet in 19F and 31P NMR spectra. The absence
of (TMS)2NF [δF(THF) Ϫ176 ppm], which is usually formed
during the electrophilic fluorination of stabilized carbanions,
prompted us to assume an equilibrium between the nitrile and
ketenimine forms of the anion, almost completely displaced in
favour of the former. It seems that the more reactive ketenimine
form is fluorinated on nitrogen to give the N-fluorophosphono-
ketenimine, but we cannot isolate the product. It is known that
acetonitrile, LiHMDS appears as the base of choice for the
metallation of benzyl cyanide (Table 2, entries 3a and 10a).
Owing to the difficulties frequently encountered in the slow
phosphorylation of stabilized benzylic anions, the use of
LiHMDS, more hindered and less basic than LDA, prevents the
competing phosphorylation of the regenerated amine and con-
sequently the protonation of the anion. For homologous alkyl
nitriles (R1 = Me, Et, Pr), LiHMDS being not strong enough
for their complete deprotonation, metallation proceeds in a
clean manner with LDA to afford diethyl 1-lithiocyanoalkyl-
3312
J. Chem. Soc., Perkin Trans. 1, 2000, 3311–3316

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Fig. 3 Crystal structure of compound 10b.
ate moieties, one oxygen [O(20)] from a water molecule, and
a nitrogen atom [N(3)] from a nitrile group which form a dis-
torted tetrahedron. The linear polymeric structure is induced by
the coordination of [N(3)] to [Li(3)] (Fig. 1).
Fig. 1 Crystal structure of compound 4b.
As expected, the P–C bond is significantly shortened (1.71 Å)
compared with 1.84 Å in the neutral compound. Similarly, the
P᎐O bond is a little longer (1.48 Å) than in 5b (1.45 Å). These
᎐
results, together with the planarity of the Li–O–P–C–P–O
ring, suggest a wide charge delocalization involving also the
nitrile group (C–C bond shortened from 1.47 Å to 1.41 Å
᎐
and C᎐N bond elongated from 1.13 Å to 1.15 Å). The Li–O
᎐
bonds of the square-planar Li(2) are longer (2.04–2.06 Å)
than those of the tetrahedral Li(1) and Li(3) (1.90–1.98 Å) or
those previously reported (1.86–1.90 Å).38 In addition to
these data, the ORTEP representation of compound 10b is
presented in Fig. 3.
Conclusions
Fig. 2 Crystal structure of compound 5b.
We report here the reaction conditions necessary in order to
obtain, in high yields and pure form, either 1-cyanomethyl-
phosphonates or 1-cyanomethylenediphosphonates. Electro-
philic halogenation of 1-cyanomethylphosphonates affords
cleanly the corresponding lithiated 1-cyanohalogenomethyl-
phosphonates, which proved to be unstable on acidic work-
up for X = Br, I. The crystal structure of lithiated 1-cyano-
methylenediphosphonate is described and it confirms the
relative inertness of this type of structure. To our knowledge,
this is the first described phosphonate anion with a polymeric
structure.
sterically hindered nitriles can be alkylated33 or silylated34 in
the ketenimine form, but a halogenation reaction of this type
has never been described.
All attempts to force the lithiated cyanomethylene-
diphosphonates 4 to react with electrophiles failed completely.
These anions are also stable in aqueous solution and are
protonated only by dil. hydrochloric acid. Fortunately, we
succeeded in obtaining X-ray-quality crystals of the anion 4b
and the crystal data are compared with those of 5b. The
corresponding ORTEP projections are presented in Figs. 1
and 2.
The solid-state structure of 5b shows two monomeric units,
with no contact between. The P–C and P–O distances (1.84 and
1.45 Å, respectively) are characteristic for neutral phosphonates
(Fig. 1). By comparison with this, the corresponding anion 4b
crystallizes as a linear polymeric aggregate with the structural
motif consisting of three lithiated diphosphonate units, with no
C–Li contact. The core of the structure is constituted by three
six-membered Li–O–P–C–P–O rings (which confirms the solu-
tion structure of diphosphonate anions35 previously postu-
lated) and two Li–O–Li–O four-membered rings, frequently
found in the structures of anionic phosphonates with no C–Li
contact.36,37 There are three types of Li atoms: (a) the central
one [Li(2)] is pentacoordinated to four oxygen atoms [O(1),
O(4), O(7), O(10)] from two equivalent diphosphonate moieties
and one oxygen atom [O(19)] from ethanol [with C(37) and
C(38)] to form a tetragonal pyramid with Li(2) almost in the
base plane; (b) the second [Li(1)] occupies the central position
of a distorted tetrahedron composed of two oxygen atoms
[O(13), O(16)] belonging to a third diphosphonate unit and two
other oxygen atoms [O(4), O(10)] coming from two different
diphosphonates; (c) the third one [Li(3)] is tetracoordinated by
two oxygen atoms [O(1), O(7)] from two different diphosphon-
Experimental
NMR spectra were recorded on a Bruker AC 200 spectrometer
operating at 200 MHz for proton, 50.3 MHz for carbon, 81.01
MHz for phosphorus and 235 MHz for fluorine. 31P down-
field shifts (δ) are expressed with a positive sign, in ppm,
relative to external 85% aq. H3PO4. 1H and 13C chemical
shifts (δ) are reported in ppm relative to CDCl3 as internal
standard. 19F chemical shifts (δ) are reported in ppm relative to
CFCl3 as external standard. Coupling constants (J ) are given in
Hz. The following abbreviations are used: s, d, t, q, p, m for
singlet, doublet, triplet, quartet, quintet (pentuplet) and multi-
plet, respectively. Low-resolution mass spectra were recorded
on a Hewlett-Packard 5989 B GC-MS spectrometer (BPX5
column, positive chemical ionization NH3). Organic solvents
were purified by standard procedures. THF was distilled
under an inert atmosphere from purple solutions of sodium–
benzophenone ketyl. The synthesis of all compounds was
carried out under dry nitrogen. ‘Evaporation’ of solvents
indicates evaporation under reduced pressure using a rotary
evaporator. All drying of solutions was done with anhydrous
magnesium sulfate.
J. Chem. Soc., Perkin Trans. 1, 2000, 3311–3316
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General method for the preparation of compounds 3a and 10–13a
4.24 (4 H, m, 2 × CH3CH2O); δC(50.3 MHz; CDCl3; Me4Si) 13.6
(s, CH3CH2CH2), 16.7 (d, 3JPC 5.7, 2 × CH3CH2O), 21.5 (d, 3JPC
n-BuLi (39.4 mL of 1.6 M solution in hexane; 63 mmol) was
added to THF (40 mL) cooled to Ϫ78 ЊC. A solution of either
1,1,1,3,3,3-hexamethyldisilazane (10.3 g, 64 mmol) (for 3a and
10a) or diisopropylamine (6.46 g, 64 mmol) (for 11a–13a) in
THF (30 mL) was then slowly added at this temperature via
a dropping funnel. After 10 min a solution of the nitrile
RЈCH2CN (30 mmol) in THF (30 mL) was slowly added at the
same temperature. After 30 min a solution of diethyl chloro-
phosphate (5.35 g, 31 mmol) in THF (30 mL) was added at
Ϫ78 ЊC. After 15 min at this temperature, the reaction mixture
was allowed to warm to 0 ЊC, then poured, with stirring, into a
mixture of 3 M HCl (50 mL), CH2Cl2 (50 mL) and ice (30 g).
The aqueous layer was extracted with CH2Cl2 (2 × 50 mL). The
combined organic layers were washed with water (10 mL), dried
and evaporated to afford the expected product, which was pure
enough for further reactions.
12.3, CH2CH2CH), 29.2 (d, 2JPC 4.4, CH2CH2CH), 30.0 (d, 1JPC
2
143.6, CH2CH2CH), 64.0 [d, JPC 6.6, (CH3CH2O)A], 64.3 [d,
2JPC 6.9, (CH3CH2O)B], 116.6 (d, 2JPC 9.5, CHCN); m/z (CI) 220
(M ϩ 1, 69), 237 (M ϩ 18, 100).
2-(ꢀ-Cyanobenzyl)-5,5-dimethyl-2-oxo-1,3,2ꢁ5-dioxaphosphor-
inane 10b. Following the general procedure for 10a, the inter-
mediate anion 6b was precipitated with conc. HCl (6 M) and
filtered. Colorless needles; δP(81.01 MHz; CDCl3; 85% H3PO4)
4.0 (s); δH(200 MHz; CDCl3; Me4Si) 1.05 [3 H, s, (CH3)A], 1.20
[3 H, s, (CH3)B], 4.13–4.29 (4 H, m, 2 × CH2O), 4.46 (1 H, d,
2JPH 27.3, CHCN), 7.41–7.56 (5 H, m, C6H5); δC(50.3 MHz;
3
CDCl3; Me4Si) 21.7 (s, CH3), 22.3 (s, CH3), 33.5 [d, JPC 9.2,
1
2
C(CH3)2], 36.9 (d, JPC 135.8, CHCN), 79.9 [d, JPC 7.6,
2
2
(CH2O)A], 80.3 [d, JPC 7.6, (CH2O)B], 116.2 (d, JPC 10.7,
2
3
CHCN), 127.8 (d, JPC 7.6, Cipso of C6H5), 129.3 (d, JPC 6.1,
5
2 × Cortho of C6H5), 129.7 (d, JPC 3.0, Cpara of C6H5), 129.9 (d,
Diethyl 1-cyanomethylphosphonate 3a.23,24 Yellowish oil
(88%); δP(81.01 MHz; CDCl3; 85% H3PO4) 15.2 (s); δH(200
4JPC 3.0, 2 × Cmeta of C6H5); m/z (CI) 254 (M ϩ 1, 100), 271
(M ϩ 18, 32).
3
MHz; CDCl3; Me4Si) 1.32 (6 H, t, JHH 7.0, 2 × CH3CH2O),
2
3
2.87 (2 H, d, JPH 21.0, CH2CN), 4.32 (4 H, dq, JHH 8.6 and
J 7.0, 2 × CH3CH2O); δC(50.3 MHz; CDCl3; Me4Si) 16.7 (d,
3JPC 6.1, 2 × CH3CH2O), 16.8 (d, 1JPC 143.3, CH2CN), 64.3 (d,
2JPC 6.6, CH3CH2O), 113.2 (d, 2JPC 7.3, CH2CN); m/z (CI) 195
(M ϩ 18, 100).
General method for the preparation of compounds 17–19
n-BuLi (6.9 mL of 1.6 M solution in hexane; 11 mmol) was
added to THF (20 mL) cooled to Ϫ78 ЊC. A solution of
1,1,1,3,3,3-hexamethyldisilazane (1.93 g, 12 mmol) in THF (10
mL) was then slowly added at this temperature via a dropping
funnel. After 10 min a solution of 3a (5 mmol) in THF (10 mL)
was slowly added at the same temperature. After 15 min a solu-
tion of halogenating agent (C2Cl6, C2Cl4Br2, I2) (5.5 mmol) in
THF (10 mL) was added at Ϫ78 ЊC and the reaction mixture
was allowed to warm to 0 ЊC, then was poured, with stirring,
into a mixture of 3 M HCl (25 mL), CH2Cl2 (25 mL) and ice
(10 g). The aqueous layer was extracted with CH2Cl2 (2 × 30
mL). The combined organic layers were washed with water
(10 mL), dried and evaporated to afford the expected product.
17 is stable at room temperature, 18 decomposed slowly on
storage and 19 decomposed during work-up.
Diethyl ꢀ-cyanobenzylphosphonate 10a.23 Yellowish oil (99%);
δP(81.01 MHz; CDCl3; 85% H3PO4) 15.0 (s); δH(200 MHz;
CDCl3; Me4Si) 1.24 [3 H, t, 3JHH 7.1, (CH3CH2O)A], 1.28 [3 H, t,
3JHH 7.1, (CH3CH2O)B], 3.94–4.21 (4 H, m, 2 × CH3CH2O),
2
4.31 (1 H, d, JPH 26.4, C6H5CHCN), 7.34–7.47 (5 H, m,
3
C6H5CHCN); δC(50.3 MHz; CDCl3; Me4Si) 16.5 (d, JPC 5.9,
2 × CH3CH2O), 36.9 (d, 1JPC 138.6, C6H5CHCN), 64.6 [d, 2JPC
2
7.3, (CH3CH2O)A], 64.9 [d, JPC 7.5, (CH3CH2O)B], 115.7 (d,
2
2JPC 9.4, C6H5CHCN), 127.9 (d, JPC 7.6, Cipso of C6H5), 128.9
(s, Cpara of C6H5), 129.0 (s, 2 × Cmeta of C6H5), 129.3 (d, 3JPC 2.6,
2 × Cortho of C6H5); m/z (CI) 254 (M ϩ 1, 60), 271 (M ϩ 18,
100).
Diethyl chloro(cyano)methylphosphonate 17. Yellowish oil
(86%); δP(81.01 MHz; CDCl3; 85% H3PO4) 8.8 (s); δH(200 MHz;
CDCl3; Me4Si) 1.45 [3 H, td, JHH 7.2 and JPH 0.8, (CH3-
Diethyl 1-cyanoethylphosphonate 11a.23,24,39,40 Yellowish oil
(89%); δP(81.01 MHz; CDCl3; 85% H3PO4) 20.4 (s); δH(200
MHz; CDCl3; Me4Si) 1.26 [3 H, t, 3JHH 7.0, (CH3CH2O)A], 1.28
3
4
3
4
CH2O)A], 1.46 [3 H, td, JHH 7.1 and JPH 0.8, (CH3CH2O)B],
3
3
2
[3 H, t, JHH 7.0, (CH3CH2O)B], 1.44 (3 H, dd, JPH 16.9 and
4.31–4.48 (4 H, m, 2 × CH3CH2O), 4.98 (1 H, d, JPH 17.5,
2
3
3JHH 7.3, CH3CH), 2.93 (1 H, dq, JPH 23.3 and JHH 7.3,
3
ClCHCN); δC(50.3 MHz; CDCl3; Me4Si) 17.0 (d, JPC 4.5,
3
3
2 × CH3CH2O), 35.5 (d, 1JPC 157.6, ClCHCN), 66.5 [d, 2JPC 5.0,
CH3CH), 4.12 [2 H, dq, JPH 8.5 and JHH 7.0, (CH3CH2O)A],
3
3
2
2
4.14 [2 H, dq, JPH 8.5 and JHH 7.0, (CH3CH2O)B]; δC(50.3
(CH3CH2O)A], 66.8 [d, JPC 6.5, (CH3CH2O)B], 113.5 (d, JPC
4.6, ClCHCN); m/z (CI) 212 (M ϩ 1 35Cl, 10), 214 (M ϩ 1 37Cl,
4), 229 (M ϩ 18 35Cl, 100), 231 (M ϩ 18 37Cl, 29).
2
3
MHz; CDCl3; Me4Si) 12.9 (d, JPC 6.0, CH3CH), 16.7 (d, JPC
5.9, 2 × CH3CH2O), 23.9 (d, 1JPC 145.2, CH3CH), 64.0 [d, 2JPC
2
7.3, (CH3CH2O)A], 64.2 [d, JPC 6.7, (CH3CH2O)B], 117.5 (d,
2JPC 9.2, CHCN); m/z (CI) 192 (M ϩ 1, 73), 209 (M ϩ 18, 100).
Diethyl bromo(cyano)methylphosphonate 18. Yellow oil;
δP(81.01 MHz; CDCl3; 85% H3PO4) 8.8 (s); δH(200 MHz;
CDCl3; Me4Si) 1.36 [3 H, 3JHH 7.1, 4JPH 0.6, td, (CH3CH2O)A],
1.37 [3 H, 3JHH 7.1, 4JPH 0.6, td, (CH3CH2O)B], 4.11–4.38 (4 H,
Diethyl 1-cyanopropylphosphonate 12a.40–42 Yellowish oil
(98%); δP(81.01 MHz; CDCl3; 85% H3PO4) 18.6 (s); δH(200
MHz; CDCl3; Me4Si) 1.17 (3 H, t, 3JHH 7.4, CH3CH2CH), 1.36
2
m, CH3CH2O), 4.50 (1 H, JPH 16.2, d, BrCHCN); δC(50.3
3
(6 H, t, JHH 7.0, 2 × CH3CH2O), 1.76–2.05 (2 H, m, CH3-
MHz; CDCl3; Me4Si) 16.7 (d, 3JPC 5.7, CH3CH2O), 17.6 (d, 1JPC
2
3
3
CH2CH), 2.84 (1 H, ddd, JPH 23.4, JHH 9.9, JHH 4.8, CH3-
155.9, BrCHCN), 66.2 [d, 2JPC 6.6, (CH3CH2O)A], 66.5 [d, 2JPC
3
3
CH2CH), 4.18 [2 H, dq, JPH 8.4 and JHH 7.0, (CH3CH2O)A],
4.21 [2 H, dq, JPH 8.4 and JHH 7.0, (CH3CH2O)B]; δC(50.3
2
7.3, (CH3CH2O)B], 113.6 (d, JPC 6.0, BrCHCN); m/z (CI)
3
3
Decomposition.
3
MHz; CDCl3; Me4Si) 13.0 (d, JPC 6.0, CH3CH2CH), 16.9 (d,
3JPC 5.9, 2 × CH3CH2O), 21.4 (d, 2JPC 44, CH3CH2CH), 32.1 (d,
Tetraethyl cyanomethylenediphosphonate 5a43
1JPC 144.1, CH3CH2CH), 64.1 [d, JPC 7.3, (CH3CH2O)A], 64.3
2
[d, 2JPC 7.1, (CH3CH2O)B], 116.7 (d, 2JPC 9.9, CHCN); m/z (CI)
206 (M ϩ 1, 59), 223 (M ϩ 18, 100).
n-BuLi (20.6 mL of 1.6 M solution in hexane; 33 mmol) was
added to THF (20 mL) cooled to Ϫ78 ЊC. A solution of diiso-
propylamine (13.43 g, 34 mmol) in THF (10 mL) was then
slowly added at this temperature via a dropping funnel. After 10
min a solution of acetonitrile (0.41 g, 10 mmol) in THF (10
mL) was slowly added at the same temperature. After 30 min a
solution of diethyl chlorophosphate (3.62 g, 21 mmol) in THF
(10 mL) was added at Ϫ78 ЊC. After 15 min at this temperature,
Diethyl 1-cyanobutylphosphonate 13a.40,41 Yellowish oil
(98%); δP(81.01 MHz; CDCl3; 85% H3PO4) 18.7 (s); δH(200
MHz; CDCl3; Me4Si) 0.90 (3 H, t, 3JHH 7.3, CH3CH2CH2), 1.30
(6 H, t, 3JHH 7.1, 2 × CH3CH2O), 1.11–1.86 (4 H, m, CH3CH2-
CH2), 2.84 (1 H, dt, 2JPH 23.5 and 3JHH 7.2, CH2CH2CH), 3.62–
3314
J. Chem. Soc., Perkin Trans. 1, 2000, 3311–3316

View Article Online
Table 3 Crystal data for the compounds 4b, 5b and 10b
Compound
4b
5b
10b
a
Molecular formula
Relative molecular mass
Crystal system
Space group
C38H68Li3N3O20P6
1096.62
Monoclinic
P21
C12H21NO6P2
337.24
Monoclinic
P21/n
C13H16NO3P
265.24
Monoclinic
P21/c
a/Å
b/Å
c/Å
α/Њ
10.5710(2)
19.5690(8)
13.0840(5)
90.00
101.141(2)
90.00
2655.60(16)
2
0.275
10.5080(5)
16.3980(7)
19.3330(8)
90.000(3)
100.048(2)
90.000(2)
3280.2(2)
8
14.4740(9)
9.4720(6)
10.5520(5)
90.00
103.753(4)
90.00
1405.18(14)
4
0.195
β/Њ
γ/Њ
V/Å3
Z
µ/cmϪ1
0.289
Reflections measured
Independent reflections
5535
5535
12028
6688
2870
2870
Rint
0.041
3638
Reflections used
4826
1963
wR2
R1
0.1158
0.0409
0.1398
0.0537
0.2486
0.0599
a 3C12H20LiNO6P2ؒC2H6OؒH2O.
the reaction mixture was allowed to warm to 0 ЊC, then was
poured, with stirring, into a mixture of 3 M HCl (25 mL),
CH2Cl2 (25 mL) and ice (10 g). The aqueous layer was extracted
with CH2Cl2 (2 × 30 mL). The combined organic layers were
washed with water (10 mL), dried and evaporated to afford the
expected product. Yellowish oil (93%); δP(81.01 MHz; CDCl3;
85% H3PO4) 9.6 (s); δH(200 MHz; CDCl3; Me4Si) 1.40 (12 H, t,
3JHH 7.0, 4 × CH3CH2O), 2.89 (1 H, d, 2JPH 21.0, CHCN), 4.21–
4.36 (8 H, m, 4 × CH3CH2O); δC(50.3 MHz; CDCl3; Me4Si)
16.2 [s, 2 × (CH3CH2O)A], 16.3 [s, 2 × (CH3CH2O)B], 30.5 (t,
1JPC 130.7, CHCN), 64.9 (s, 4 × CH3CH2O), 111.7 (t, 2JPC 10.4,
CHCN); m/z (CI) 314 (M ϩ 1, 100), 331 (M ϩ 18, 25).
fractometer using MoKα radiation (λ = 0.7107 Å). The crystal
structures were solved with maXus. While initial refinement was
performed with the latter, final least-squares was conducted
with SHELXl-97.44 Illustrations were made using PLATON.45
Crystal data are assembled in Table 3. Atomic coordinates,
bond lengths and angles, and thermal parameters for com-
pounds 4b, 5b and 10b have been deposited at the Cambridge
Crystallographic Data Centre. CCDC reference number
207/465. See http://www.rsc.org/suppdata/p1/b0/b003371p for
crystallographic files in .cif format.
Acknowledgements
1-Cyanomethylenebis(5,5-dimethyl-2-oxo-1,3,2ꢁ5-dioxa-
phosphorinane) 5b. Following the procedure for 5a, the inter-
mediate anion 4b was precipitated with conc. HCl (6 M) and
filtered. Colorless plates (40–50%); δP(81.01 MHz; CDCl3; 85%
H3PO4) Ϫ0.2 (s); δH(200 MHz; CDCl3; Me4Si) 1.01 [6 H, s,
2 × (CH3)A], 1.35 [6 H, s, 2 × (CH3)B], 4.15 (4 H, dd, 3JPHax 17.7
and JHaxHeq 10.6, 2 × CH2Oax), 4.58 (4 H, dd, JPHeq 3.2 and
2JHaxHeq 11.0, CH2Oeq), CH exchanged with CDCl3; δC(50.3
MHz; CDCl3; Me4Si) 21.1 [s, 2 × (CH3)A], 22.6 [s, 2 × (CH3)B],
29.8 (t, 1JPC 124.8, CHCN), 33.4 {d, 3JPC 4.4, [C(CH3)2]A}, 33.5
{d, 3JPC 4.4, [C(CH3)2]B}, 80.3 (s, 4 × CH2O), 112.1 (t, 2JPC 10.7,
CHCN); m/z (CI) 338 (M ϩ 1, 100), 355 (M ϩ 18, 88).
We thank Elf Atochem S.A. for financial support to B. I., and
Dr M. Levard (UMR 7652) of the Ecole Polytechnique for the
mass spectra.
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