Synthesis of polyfunctionalized methylphosphine oxides

Article abstract of DOI:10.1007/s11172-012-0053-2

N,N-Dialkylamino(diphenylphosphoryl)chloromethanes, a new type of organophosphorus compounds, were synthesized. On dissolving in polar and low polar solvents, N,N-dialkylamino(diphenylphosphoryl)chloromethanes dissociate spontaneously with the P - C bond cleavage to form the diphenylphosphinite anion Ph₂PO^-. This was confirmed by the reaction of N,N-dimethylamino(diphenylphosphoryl)chloromethane with electrophilic substrates to form the corresponding addition or substitution products of Ph ₂PO^-. The capability of spontaneous generating the diphenylphosphinite anion considers accessible N,N- dimethylamino(diphenylphosphoryl)chloromethane as a synthetic equivalent of the diphenylphosphinite anion.

Full text of DOI:10.1007/s11172-012-0053-2

Russian Chemical Bulletin, International Edition, Vol. 61, No. 2, pp. 380—385, February, 2012
380
Synthesis of polyfunctionalized methylphosphine oxides
V. P. Morgalyuk, T. V. Strelkova, and E. E. Nifant´ev
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6549. Eꢀmail: morgaliuk@mail.ru
N,NꢀDialkylamino(diphenylphosphoryl)chloromethanes, a new type of organophosphorus
compounds, were synthesized. On dissolving in polar and low polar solvents, N,Nꢀdialkylꢀ
amino(diphenylphosphoryl)chloromethanes dissociate spontaneously with the P—C bond cleavꢀ
age to form the diphenylphosphinite anion Ph2PO–. This was confirmed by the reaction of
N,Nꢀdimethylamino(diphenylphosphoryl)chloromethane with electrophilic substrates to form
the corresponding addition or substitution products of Ph2PO–. The capability of spontaneous
generating the diphenylphosphinite anion considers accessible N,Nꢀdimethylamino(diphenylꢀ
phosphoryl)chloromethane as a synthetic equivalent of the diphenylphosphinite anion.
Key words: functionalized phosphine oxides, diphenylchlorophosphine, N,Nꢀdialkylaminoꢀ
(diphenylphosphoryl)chloromethanes, N,Nꢀdialkylaminobis(diphenylphosphoryl)methanes,
N,Nꢀdialkylchloromethylideneiminium chloride, diphenylphosphinite anion, dissociation.
Scheme 1
Trisꢀsubstituted methanes functionalized by dipheꢀ
nylphosphoryl and dialkoxyphosphoryl groups are highly
reactive. The phosphorus—carbon bond1 is cleaved upon
the reaction of functionalized methanes with strong acids
and bases, which found use in the modern synthetic
chemistry. For instance, dialkoxy(diphenylphosphoryl)ꢀ
methanes react with aldehydes and ketones in the Horꢀ
ner—Wadsworth—Emmons reaction to form ketene aceꢀ
tals.2 Dialkoxy(dialkoxyphosphoryl)methane derivatives
are presently used in bioorganic and medicinal chemistry
for the temporal protection of the hydrophosphoryl group3
and as synthetic equivalents (synthones) of phosphinic
acids3a,b,e,4 and formyl anion in the synthesis of carbonyl
compounds.5
It has previously been reported6 that the reaction of
diphenylchlorophosphine Ph2PCl (1) with N,Nꢀdialkylꢀ
formamides Alk2NC(H)O (2) in the presence of catalytꢀ
ic amounts (5—15 mol.%) of N,Nꢀdialkylchloromethylꢀ
ideneiminium chlorides [Alk2N=C(H)Cl]+Cl– (3) affords
N,Nꢀdialkylamino(diphenylphosphoryl)chloromethanes
4a,e (Scheme 1). Compounds 4b—d were synthesized in
the present work.
N,NꢀDialkylchloromethylideneiminium chlorides 3
can be synthesized directly in the reaction medium6 by the
reaction of N,Nꢀdialkylformamides 2 with PhP(O)Cl2 (5),
(COCl)2 (6), PCl5 (7), and SOCl2 (8). Compounds 3 were
shown to be reactantꢀcatalysts recoverable during the reꢀ
action, and their formation in the reaction medium allows
the synthesis of N,Nꢀdialkylamino(diphenylphosphoryl)ꢀ
chloromethanes 4 to occur (see Scheme 1), as it has been
proposed earlier6 and then experimentally confirmed.7
It has been shown6b that the 31P NMR spectra of comꢀ
pounds 4а and 4e recorded in CDCl3 contain two signals of
phosphorus atoms: for 4а, at P 25.9 (80%) and 21.1 (20%)
and for 4e, at P 34.9 (11%) and 25.9 (89%). At the
moment, we would not be able to explain this phenomenon.
Dissociation of N,Nꢀdialkylamino(diphenylphosphoryl)ꢀ
chloromethanes 4 at the P—C bond. The unusual behavior
of dialkylamino(diphenylphosphoryl)chloromethanes was
1
studied by Н and 31Р NMR spectroscopy using phosꢀ
phine oxide 4a as the most accessible derivative of comꢀ
1
pounds 4 as an example. It turned out that the Н and
31Р NMR spectra of compound 4а detected in CDCl3
changed substantially with time.
1
The 31Р NMR spectrum (without Н decoupling)
detected immediately after the dissolution of comꢀ
pound 4а in CDCl3 exhibits the signal at P 22.0 with the
2
farꢀrange spinꢀspin coupling constant JP,H = 11 Hz,
which confirms the presence of the Р—С—Н fragment
2
in the compound, and the corresponding to JP,H of the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 378—383, February, 2012.
1066ꢀ5285/12/6102ꢀ380 © 2012 Springer Science+Business Media, Inc.

Polyfunctionalized methylphosphine oxides
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
381
1
same fragment appeared in the Н NMR spectrum as
ion Ph2PO– (13). The latter further readily substitutes the
chlorine atom in the initial 4а to form compound 9а.
a doublet at H 7.89. Thus, the Н and 31Р NMR spectra
1
of compound 4а correspond to its structural formula,
as well as the Xꢀray diffraction6 and elemental analyses
results.
Scheme 3
Ten minutes after the dissolution of compound 4а in
CDCl3 at 5 С, a signal of another compound appears in
the 31Р NMR spectrum at P 26.0, whose intensity inꢀ
creases with time. The intensity of the 31Р signal of the
initial 4а at P 22.0 simultaneously decreases. After 18 h,
the 31Р NMR spectrum of the reaction system contains
only a signal at P 26.0. The signal at P 26.0 appears as
a singlet in the 31Р NMR spectrum detected without
1Н decoupling. In this case, the 1Н NMR spectrum of the
reaction mixture contains two signals as singlets at Н 11.14
and 3.85 with the 1 : 6 intensity ratio, which is close to the
1Н NMR spectrum of N,Nꢀdimethylchloromethylideneꢀ
iminium chloride [Me2N=C(H)Cl]+Cl– (3а, Vilsmeierꢀ
Haak reagent) synthesized by a described procedure8 for
comparison. The 1Н NMR spectrum of compound 3а also
exhibits two signals: at Н 11.18 (H—С(Cl) group) and
3.91 (N(CH3)2 group) with the 1 : 6 intensity ratio. This
indicates the presence of the N,Nꢀdimethylchloromethꢀ
ylideneiminium cation [Me2N=C(H)Cl]+ (3´а) in the reꢀ
action mixture. After the workꢀup of the reaction mixture,
N,Nꢀdimethylaminobis(diphenylphosphoryl)methane (9а)
was isolated in high yield (85%), and its 31Р NMR specꢀ
trum exhibits a signal at Р 26.0.
However, unlike compounds 10, 11, and 12, neither
heating with hydrochloric acid1,3 or a solution of NaI,10
nor lithiation at low temperatures5b,e are required for
the P—C bond cleavage in compound 4а. The dissociaꢀ
tion of compound 4а at the P—C bond followed by the
formation of compounds 3´а and 13 occurs simultaneously
upon dissolution in low polar (CHCl3) or polar (DMF)
solvents.
It can be assumed that in DMF (more polar solvent
than CHCl3) the dissociation of compound 4а to comꢀ
pounds 3´а and 13 with the subsequent formation of comꢀ
pound 9а is faster than the same process in CHCl3. Thereꢀ
fore, the 31Р NMR spectra detected immediately after the
dissolution of compound 4а in DMF exhibit only one
signal6 at H 26.0 corresponding to compound 9а as a final
product (see Scheme 2).
The change observed in the spectra can be explained by
the fact that in solution two molecules of 4а can interact
with each other (Scheme 2) to form N,Nꢀdimethylꢀ
chloromethylideneiminium chloride (3a) and N,Nꢀdiꢀ
methylaminobis(diphenylphosphoryl)methane (9а).9
Synthesis of N,Nꢀdialkylamino(diphenylphosphoryl)ꢀ
chloromethanes 4b—d. To confirm that the ability of molꢀ
ecules of N,Nꢀdialkylamino(diphenylphosphoryl)chloroꢀ
methanes 4 to react between each other is a common
property, we synthesized a series of compounds in which
the Alk2N substituent is the diethylamino group (N,Nꢀdiꢀ
ethylamino(diphenylphosphoryl)chloromethane (4b)),
pyrrolidino group ((diphenylphosphoryl)pyrrolidinochloroꢀ
methane (4c)), piperidino group ((diphenylphosphoryl)ꢀ
piperidinochloromethane (4d)), and morpholino group
((diphenylphosphoryl)morpholinochloromethane (4e))
(see Scheme 1). It was shown that the presence of a cataꢀ
lytic amount of 1,4ꢀdioxane (14) in the reaction mixture
exerts a substantial effect on the reaction course. In the
presence of 14, the synthesis of compounds 4а and 4e
occurs more rapidly than in the absence of 14.6b Moreꢀ
over, it turned out that it is impossible to synthesize
compounds 4b—d under the reaction conditions6 in the
absence of dioxane (14) (see Scheme 1). The activatꢀ
ing (promoting) effect of compound 14 in the synthesis
of compounds 4а—e can be explained by its ability to solꢀ
vate the N,Nꢀdialkylchloromethylideneiminium cation
[Alk2N=C(H)Cl]+ (3´а) with the formation of the oxoniꢀ
Scheme 2
In turn, the transformation considered can be exꢀ
plained by the fact that in solutions compound 4а,
by analogy to dialkoxy(dialkoxyphosphoryl)methanes
(AlkO)2P(O)C(H)(OAlk)2 (10),1 (diphenylphosphoryl)ꢀ
diethoxymethane Ph2P(O)C(H)(OEt)2 (11),5b,e and
benzyl (diphenylphosphoryl)formate Ph2P(O)C(O)OBn
(12),10 can decompose with the P—C bond cleavage
(Scheme 3) to form the N,Nꢀdimethylchloromethylꢀ
ideneiminium cation (3´а) and diphenylphosphinite anꢀ

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Morgalyuk et al.
Scheme 5
um cation (3а) (see Scheme 4). The electrophilic center
of the latter, viz., N,Clꢀdisubstituted carbocation, is more
accessible for the nucleophilic attack of diphenylchloroꢀ
phosphine 1 by the phosphorus atom compared to iminiꢀ
um cation 3´а. As a result, this accelerates the synthesis of
compounds 4а and 4e and makes it possible to synthesize
compounds 4b—d.
Scheme 4
that the reaction of molecules of compounds 4 between
each other is sterically controlled.
1
It should be mentioned that the H and 13С NMR
spectra of N,Nꢀdialkylaminobis(diphenylphosphoryl)ꢀ
methanes 9a,c—e have a number of specific features. For
1
example, in the H NMR spectra of compounds 9a,c—e
the signals of the hydrogen atoms in the orthoꢀpositions of
the phenyl substituents at the phosphoryl groups appear as
two groups of signals at H 8.04—7.98 and 7.82—7.75.
Similarly, the ipsoꢀcarbon atoms of the phenyl substituꢀ
ents at the phosphoryl groups appear as two doublets of
doublets with nearly coinciding chemical shifts at С
133.3—132.1 and different spinꢀspin coupling constants
JP,C. For N,Nꢀdimethylaminobis(diphenylphosphoryl)ꢀ
methane 9a, the first doublet of doublets is observed at
This, in turn, confirms the key role of N,Nꢀdialkylꢀ
chloromethylideneiminium chlorides 3 as reactantꢀcataꢀ
lysts7 in the synthesis of N,Nꢀdialkylamino(diphenylꢀ
phosphoryl)chloromethanes 4 from N,Nꢀdialkylformꢀ
amides 2 and 1.
N,NꢀDialkylamino(diphenylphosphoryl)chloromethꢀ
anes 4b—d are precipitated from the reaction mixture as
compounds of nonstoichiometric compositions with hyꢀ
drogen chloride (the content of HCl was 0.15—0.5 mole
(mole of 4b—d)–1). Perhaps, this is caused by the higher
basicity of the diethylaminoꢀ, pyrrolidinoꢀ, and piperidiꢀ
no groups of compounds 4b—d compared to the dimethylꢀ
aminoꢀ and morpholino groups of compounds 4a and 4e.
However, after keeping N,Nꢀdialkylamino(diphenylphosꢀ
phoryl)chloromethanes 4b—d over fresh NaOH in vacuo
for 2 days, their elemental analysis becomes consistent
with the empirical formula.
Synthesis of N,Nꢀdialkylaminobis(diphenylphosphoryl)ꢀ
methanes 9c—e. Of the synthesized N,Nꢀdialkylaminoꢀ
(diphenylphosphoryl)chloromethanes, molecules of comꢀ
pounds 4с—e also interact with each other. After dissoluꢀ
tion in CHCl3, they are rapidly transformed into bisꢀ
(diphenylphosphoryl)pyrrolidinomethane (9c), bis(diꢀ
phenylphosphoryl)piperidinomethane (9d), and bis(diꢀ
phenylphosphoryl)morpholinomethane (9e). Thus, it can
be assumed that, upon dissolution of N,Nꢀdialkylaminoꢀ
(diphenylphosphoryl)chloromethanes 4 in aprotic low
polar (CHCl3, СН2Cl2) and polar (DMF) solvents, their
molecules, similarly to compound 4a, react with each other
to form N,Nꢀdialkylaminobis(diphenylphosphoryl)methꢀ
anes 9 (Scheme 5).
Only N,Nꢀdiethylamino(diphenylphosphoryl)chloroꢀ
methane (4b) does not enter the reaction. Perhaps, this is
explained by greater steric hindrances caused by the diethylꢀ
amino group upon the attack of the diphenylphosphinite
anion Ph2PO– (13) on the trisꢀsubstituted carbon atom of
compound 4b as compared to 4a and compounds 4c—e
containing the Nꢀheterocyclic fragment. It can be assumed
3
С 133.3 (1JP,C = 118.4 Hz and JP,C = 11.0 Hz) and the
second doublet is observed at С 133.1 (1JP,C = 97.1 Hz
and 3JP,C = 10.3 Hz). A similar, although less pronounced
pattern is observed for signals of the carbon atoms in the
orthoꢀ and metaꢀpositions of the phenyl substituents. The
13С NMR spectra of other N,Nꢀdialkylaminobis(diphenylꢀ
phosphoryl)methanes 9c—e are also similar to the 13С NMR
spectrum of compound 9a. This is due to diastereotopicity
of the phenylic hydrogen and carbon atoms in molecules
of compounds 9a,c—e, resulting in their magnetic nonꢀ
1
equivalence, which is observed in the H and 13С NMR
spectra. In these spectra, the nonequivalent hydrogen atꢀ
oms in the orthoꢀpositions and the ipsoꢀcarbon atoms (and
the carbon atoms in the orthoꢀ and metaꢀpositions) of the
phenyl substituents at the phosphoryl groups appear as
particular groups of signals.
Reactions of N,Nꢀdimethylamino(diphenylphosphoryl)ꢀ
chloromethane (4a) with electrophilic substrates. We failed
to detect a signal from diphenylphosphinite anion 13 in
the 31P NMR spectra of the reaction mixtures. Therefore,
to check the assumption about the existence of nucleoꢀ
philic diphenylphosphinite anion 13 in solutions of N,Nꢀdiꢀ
alkylamino(diphenylphosphoryl)chloromethanes 4, the
most accessible of them, namely, N,Nꢀdimethylaminoꢀ
(diphenylphosphoryl)chloromethane 4а, was reacted with
acetone (15), phenyl isocyanate (16), and bis(N,Nꢀdiꢀ
ethylamino)methane (17), which are pronounced electroꢀ
philic substrates, and also with the acetonitrile complex of
Pd+2, PdCl2•(CH3CN)2 (18).
In all cases, compound 4а reacted in such a way as it
could be expected from the assumption that diphenylphosꢀ

Polyfunctionalized methylphosphine oxides
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
383
phinite anion 13 exists in the reaction medium (Scheme 6).
The corresponding products of addition or substitution of
the diphenylphosphinite anion were obtained: 2ꢀ(diꢀ
phenylphosphoryl)propanꢀ2ꢀol (19) (see Ref. 11), Nꢀphenylꢀ
(diphenylphosphoryl)formamide (20) (see Ref. 12),
N,Nꢀdiethylaminomethyldiphenylphosphine oxide (21)
(see Ref. 13), and cisꢀbis(Pꢀhydroxydiphenylphosꢀ
phine)palladium(II) chloride (22) (see Ref. 14),
which confirms the existence of diphenylphosphinite anꢀ
ion 13 in the reaction medium and spontaneous dissoꢀ
ciation of compound 4а as well as, obviously, other
N,Nꢀdialkylamino(diphenylphosphoryl)chloromethanes 4
at the Р—С bond.
Experimental
1
Н, 31Р, and 13С NMR spectra were recorded on a Bruker
Avance 300 spectrometer with working frequencies of 300.11,
121.50, and 75.45 MHz, respectively. The 1Н and 31Р NMR
spectra of individual compounds were detected in CDCl3; the
31Р NMR spectra of the reaction mixtures were also recorded in
DMF, СНCl3, and СН2Cl2 using 85% Н3РО4 as an external
standard. Melting points were determined on a PTP instrument
in a sealed capillary. Elemental analyses to C, H, and N were
carried out on a Carlo Erba 1106 automated analyzer. Elemental
analysis to P was performed spectrophotometrically on a Cary
100 Scan instrument. Elemental analysis to Cl was conducted by
titration with 1 mM AgNO3.
N,NꢀDimethylamino(diphenylphosphoryl)chloromethane (4a).
Oxalyl chloride COCl2 (6) (0.17 g, 0.12 mL, 1.3 mmol) and
five—seven droplets of dioxane 14 were slowly added dropwise
to a mixture of DMF (2а) (6 mL) and benzene (2 mL) at 0 С
with stirring. Then Ph2PCl (1) (2 g, 9.1 mmol) was added under
inert atmosphere with stirring at 20 С. After 0.5 h, the reaction
mixture turned redꢀbrown and analytically pure 4a* began to
precipitate. Benzene (10 mL) was added to the reaction mixture
8 h after, and the mixture was stirred for 5 min. The reaction
mixture was kept for 1 h at 0 С, and the precipitate was filtered
off, washed with benzene (3×5 mL), and dried for 2 days in vacuo
(1 Torr) over P2O5. Compound 4a was obtained in a yield of 2.42 g
(91%). Colorless hygroscopic needles, m.p. 92—94 С (with deꢀ
Scheme 6
2
comp.). 31Р NMR, : 22.0 (d, JP,H = 11.0 Hz). 1Н NMR,
: 8.00—7.93 (m, 4 H, oꢀH, Ph); 7.89 (d, 1 Н, СН, 2JP,H = 11.0 Hz);
7.56—7.49 (m, 6 H, mꢀH, pꢀH, Ph); 3.08 (s, 6 H, N(CH3)2).
Found (%): C, 61.44; H, 5.79; N, 4.68; P, 10.40. C15H17ClNOP.
Calculated (%): C, 61.34; H, 5.83; N, 4.77; P, 10.55.
Compounds 4b—e were synthesized similarly.
N,NꢀDiethylamino(diphenylphosphoryl)chloromethane (4b).
The reaction time was 3 days. The yield was 47%. Light yellow
hygroscopic substance, m.p. 74—77 С (with decomp.). 31Р{1H}
2
NMR, : 18.8 (s). 1Н NMR, : 10.48 (d, 1 Н, СН, JP,H
=
= 23.0 Hz); 8.25—8.19 (m, 4 H, oꢀH, Ph); 7.62—7.53 (m, 6 H,
mꢀH, pꢀH, Ph); 4.21 (q, 4 H, 2 СН2, 3JH,H = 6.0 Hz); 1.34 (br.s,
6 H, 2 СН3, 
= 24 Hz). Found (%): C, 61.65; H, 6.31;
1/2
N, 4.28; P, 9.21; Cl, 13,05. C17H21NClOP•0.25HCl. Calculatꢀ
ed (%): C, 61.70; H, 6.40; N, 4.23; P, 9.35; Cl, 13.39. After
drying in vacuo (1 Torr) over NaOH, found (%): C, 63.46;
H, 6.74; N, 4.31; P, 9.55; Cl, 10.94. C17H21NPClO. Calculatꢀ
ed (%): C, 63.45; H, 6.58; N, 4.35; P, 9.62; Cl, 11.02.
i. Me2C=O (15); ii. Ph—N=C=O (16); iii. (Et2N)2CH2 (17);
iv. PdCl2(MeCN)2 (18).
(Diphenylphosphoryl)pyrrolidinochloromethane (4c). The
reaction time was 2 days. The yield was 72%. Pale orange hygroꢀ
scopic substance, m.p. 79—82 С (with decomp.). 31Р{1H} NMR,
: 19.3 (s). Н NMR, : 10.31 (d, 1 Н, СН, JP,H = 23.0 Hz);
8.20—8.13 (m, 4 H, oꢀH, Ph); 7.61—7.49 (m, 6 H, mꢀH, pꢀH,
Spontaneous dissociation of N,Nꢀdialkylamino(diꢀ
phenylphosphoryl)chloromethanes (4a,с—e) in solutions
with the P—C bond cleavage makes it possible to consider
them as a hidden form of the diphenylphosphinite anion
Ph2PO– (13). This allows the most accessible of them,
N,Nꢀdimethylamino(diphenylphosphoryl)chloromethane
(4a), to be used in organic and organoelement syntheses
as a synthetic equivalent (synthone) of diphenylphosꢀ
phinite anion 13 instead of the traditional source of the
diphenylphosphinite anion, diphenylphosphine oxide (15),
which requires a strong base15 in the reaction medium for
the generation of Ph2PO– (13) and tends to oxidation and
disproportionation.16
1
2
Ph); 4.22 (s, 4 H, 2 NСН2); 2.03 (br.s, 4 H, 2 СН2, 
=
1/2
= 15 Hz). Found (%): C, 62.39; H, 6.07; N, 4.23; P, 9.47;
Cl, 11.93. С17H19NClOP•0.15HCl. Calculated (%): C, 62.85;
* It is impossible to purify compound 4а by recrystallization,
reprecipitation, or chromatography, because in solutions the
compound reacts with another molecule of 4a. Therefore, anaꢀ
lytically pure 4а was isolated carrying out the reaction in
a DMF—benzene mixture used for the recrystallization of strucꢀ
turally similar compounds.

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Morgalyuk et al.
H, 5.93; N, 4.31; P, 9.53; Cl, 12.44. After drying in vacuo
(1 Torr) over NaOH, found (%): C, 63.19; H, 5.90; N, 4.43;
P, 9.47. С17H19NClOP. Calculated (%): C, 63.85; H, 5.99;
N, 4.38; P, 9.69.
N, 2.59; Р, 12.47. С29Н29NО2Р2•1/2H2O. Calculated (%):
С, 70.44; Н, 6.12; N, 2.83; Р, 12.52.
Bis(diphenylphosphoryl)piperidinomethane (9d). The yield was
53%. White substance, m.p. 187—189 С. 31Р{1H} NMR, : 27.9
1
(Diphenylphosphoryl)piperidinochloromethane (4d). The reacꢀ
tion time was 3 days. The yield was 65%. Light yellow hygroꢀ
scopic substance, m.p. 85—88 С (with decomp.), 31Р{1H} NMR,
(s). Н NMR, : 8.01 (br.s, 4 Н, oꢀН, Ph,  = 18 Hz); 7.78
1/2
(br.s, 4 Н, oꢀН, Ph,  = 18 Hz); 7.50–7.26 (m, 12 Н, mꢀН,
1/2
pꢀН, Ph); 4.64 (br.s, 1 Н, СН, 1/2 = 45 Hz); 2.92—2.86 (m, 4 Н,
1
2
: 20.2 (s). Н NMR, : 9.78 (d, 1 Н, СН, JP,H = 21.0 Hz);
8.17—8.09 (m, 4 H, oꢀH, Ph); 7.62—7.51 (m, 6 H, mꢀH, pꢀH,
2 NСН2); 1.20 (br.s, 6 Н, СН2СН2СН2, 
= 27 Hz).
1/2
13C NMR, : 133.3 (dd, PC, Ph, JP,C = 95.1 Hz, JP,C = 7.5 Hz);
133.0 (dd, PC, Ph, JP,C = 119.0 Hz, JP,C = 7.5 Hz); 131.8 (ddd,
oꢀС, Ph, JP,C = 4.6 Hz, JP,C = 4.9 Hz, JP,C = 8.9 Hz); 131.5
(s, pꢀС, Ph); 128.1 (dddd, mꢀС, Ph, JP,C = 25.0 Hz, JP,C = 6.0 Hz,
JP,C = 13.2 Hz, JP,C = 5.8 Hz); 70.6 (t, CH, JP,C = 61.8 Hz);
53.9 (s, NСН2); 26.1 (s, СН2СН2СН2); 23.3 (s, СН2СН2СН2).
Found (%): С, 71.82; Н, 6.06; N, 2.97; Р, 12.25. С30Н31NО2Р2.
Calculated (%): С, 72.13; Н, 6.26; N, 2.80; Р, 12.40.
3
Ph); 4.12 (t, 4 H, 2 NСН2, JH,H = 6.0 Hz); 1.82 (br.s, 4 H,
СН2СН2СН2, 
= 11 Hz); 1.64 (q, 2 H, СН2СН2СН2,
1/2
3JH,H = 6.0 Hz). Found (%): C, 61.64; H, 6.46; N, 3.85; P, 9.17.
C18H21NClOP•0.5HCl. Calculated (%): C, 61.72; H, 6.16;
N, 3.98; P, 8.80. After drying in vacuo (1 Torr) over NaOH,
found (%):C, 64.84; H, 6.48; N, 3.95; P, 9.26. C18H21NClOP.
Calculated (%): C, 64.77; H, 6.34; N, 4.20; P, 9.28.
(Diphenylphosphoryl)morpholinochloromethane (4e). The reacꢀ
tion time was 18 h. The yield was 86%. Colorless hygroscopic
needles, m.p. 70—71 С (with decomp.). 31Р{1H} NMR, : 27.9
(s). 1Н NMR, : 7.91—7.81 (m, 4 H, oꢀH, Ph); 7.61—7.54 (m, 2 H,
mꢀH, Ph); 7.52—7.45 (m, 4 H, pꢀH, Ph); 6.19 (d, 1 H, CH,
2JP,H = 4.0 Hz); 3.61—3.55 (m, 4 H, OCH2); 3.08 (t, 4 H,
NCH2, 3JH,H = 5.0 Hz). Found (%): C, 60.32; H, 5.90; N, 4.10;
P, 9.11. C17H19NPClO2. Calculated (%): C, 60.71; H, 5.70;
N, 4.17; P, 9.22.
Bis(diphenylphosphoryl)morpholinomethane (9e). The yield
was 41%. White substance, m.p. 172—174 С. 31Р{1H} NMR, :
28.3 (s). 1Н NMR, : 7.99—7.93 (m, 4 Н, oꢀН, Ph); 7.93—7.72
(m, 4 Н, oꢀН, Ph); 7.40—7.24 (m, 12 Н, mꢀН, pꢀН, Ph); 3.61
2
2
(t, 1 Н, СН, JP,H = 17.0 Hz); 3.15 (t, 4 Н, 2 OСН2, JH,H
=
= 4.0 Hz); 2.83 (br.s, 4 Н, 2 NСН2, 1/2 = 22 Hz). 13C NMR,
: 132.9 (dd, PC, Ph, JP,C = 115.5 Hz, JP,C = 29.8 Hz); 132.1
(dd, PC, Ph, JP,C = 98.5 Hz, JP,C = 26.7 Hz); 131.7—131.5
(m, oꢀС, pꢀС, Ph); 128.3 (dddd, mꢀС, Ph, JP,C = 18.3 Hz, JP,C
= 5.8 Hz, JP,C = 6.3 Hz, JP,C = 6.0 Hz); 69.4 (t, CH, JP,C
=
=
N,NꢀDimethylaminobis(diphenylphosphoryl)methane (9a).
A solution of 4a (3.4 g, 11.6 mmol) in 20 mL of CHCl3 freshly
distilled over P2O5 was kept for 18 h at 5 С. The solution was
diluted with CH2Cl2 (30 mL) and washed with water (4×5 mL).
The organic layer was separated and dried with MgSO4. The
drying agent was filtered off and washed with CH2Cl2 (4×5 mL).
The filtrate was evaporated to a volume of ~5 mL. Hexane
(40 mL) was added, and the mixture was cooled to –10 С. After
18 h, the precipitate formed was filtered off, washed with hexane
(4×5 mL) cooled to 0 С, and doubly reprecipitated with hexane
from CH2Cl2. Compound 9a was obtained in a yield of 2.25 g
(85%). Colorless needles, m.p. 207—210 С (cf. Ref. 9: m.p.
210–212 С). 31Р{1H} NMR, : 27.3 (s). 1Н NMR, : 8.04—7.98
(m, 4 Н, oꢀН, Ph); 7.82—7.76 (m, 4 Н, oꢀН, Ph); 7.47—7.37
(m, 8 Н, mꢀН, Ph); 7.33–7.28 (m, 4 Н pꢀH, Ph); 4.63 (t, 1 Н,
= 61.5 Hz); 67.3 (s, OСН2); 52.9 (s, NСН2). Found (%):
С, 69.23; Н, 5.96; N, 2.71; Р, 12.15. С29Н29NО3Р2. Calculatꢀ
ed (%): С, 69.45; Н, 5.83; N, 2.79; Р, 12.35.
2ꢀ(Diphenylphosphoryl)propanꢀ2ꢀol (19). Acetone (15) (3.0 mL,
2.4 g, 40 mmol) was added with stirring to a solution of 4a (0.3 g,
1 mmol) in CH2Cl2 (1.5 mL). The mixture was kept for 18 h at
20 С. The precipitate that formed was dissolved in CH2Cl2
(10 mL) without separating from the solution and washed with
water (4×5 mL). The organic layer was separated and dried with
K2CO3. The drying agent was filtered off, and the filtrate was
washed with CH2Cl2 (2×5 mL) and concentrated to a volume of
~1 mL. Hexane (8 mL) was added, and the precipitate formed
was double reprecipitated with hexane from a solution in CHCl3.
Compound 19 as colorless needles was obtained in a yield of 0.26 g
(87%), m.p. 137—139 С (cf. Ref. 11: m.p. 141—143 С).
31Р{1H} NMR, : 34.4 (s). 1Н NMR, : 8.04—7.97 (m, 4 H, oꢀH,
Ph); 7.53—7.43 (m, 6 H, mꢀH, pꢀH, Ph); 2.75 (d, 1 H, OH,
2
СН, JP,H = 18.0 Hz); 2.50 (s, 6 Н, N(CH3)2). 13C NMR, :
133.3 (dd, PC, Ph, JP,C = 118.4 Hz, JP,C = 11.0 Hz); 133.1 (dd,
PC, Ph, JP,C = 97.1 Hz, JP,C = 10.3 Hz); 131.9 (dddd, oꢀС, Ph,
JP,C = 16.1 Hz, JP,C = 4.8 Hz, JP,C = 6.3 Hz, JP,C = 5.0 Hz);
3
3JP,H = 3.0 Hz); 1.44 (d, 6 H, 2 CH3, JP,H = 15.0 Hz).
131.6 (s, pꢀС, Ph); 128.1 (ddd, mꢀС, Ph, JP,C = 5.8 Hz, JP,C
=
Found (%): С, 68.97; Н, 6.28; Р, 11.63. С15Н17О2Р. Calculatꢀ
ed (%): С, 69.22; Н, 6.59; Р, 11.90.
= 6.0 Hz, JP,C = 11.8 Hz); 69.2 (t, CH, JP,C = 62.5 Hz); 45.1
(t, NСН3, JP,C = 3.3 Hz). Found (%): С, 70.07; Н, 5.95; N, 2.82;
Р, 13.34. С27Н27NО2Р2. Calculated (%): С, 70.58; Н, 5.92;
N, 3.05; Р, 13.48.
(Diphenylphosphoryl)ꢀNꢀphenylformamide (20). Phenyl isoꢀ
cyanate (16) (0.4 g, 3.5 mmol) was added to 4a (0.5 g, 1.7 mmol)
partially dissolved in CH2Cl2 (2 mL). The mixture was stirred at
20 С. Compound 4a was entirely dissolved within 48 h. The
mixture was stirred for 10 h more, diluted with CH2Cl2 (10 mL),
and washed with water (4×5 mL). The organic layer was separatꢀ
ed and dried with K2CO3. The drying agent was filtered off and
washed with CH2Cl2 (2×5 mL), and the filtrate was concentratꢀ
ed to a volume of ~2 mL. Hexane (8 mL) was added. The precipꢀ
itate formed was doubly reprecipitated with hexane from a soluꢀ
tion in CH2Cl2. Compound 20 was obtained as colorless needles
in a yield of 0.41 g (75%), m.p. 160—162 С (cf. Ref. 12: m.p.
161—162 С). 31Р{1H} NMR, : 15.9 (s). 1Н NMR, : 9.55 (s, 1 H,
NH); 7.98—7.91 (m, 4 Н, oꢀН, PhP); 7.64 (d, 2 Н, pꢀH, PhP);
7.61—7.56 (m, 2 Н, mꢀH, PhN); 7.52—7.46 (m, 4 Н, mꢀH,
Compounds 9с—e were synthesized similarly.
Bis(diphenylphosphoryl)pyrrolidinomethane hemihydrate (9c).
The yield was 34%. White substance, m.p. 156—159 С. 31Р{1H}
1
NMR, : 28.6 (s). Н NMR, : 8.04—7.98 (m, 4 H, oꢀH, Ph);
7.82—7.76 (m, 4 H, oꢀH, Ph); 7.47—7.37 (m, 8 H, mꢀH, Ph);
7.36—7.27 (m, 4 Н, pꢀН, Ph); 4.97 (t, 1 Н, СН, 2JP,H = 17.4 Hz);
2.90 (br.s, 4 Н, 2 NСН2, 
= 15 Hz); 1.43 (br.s, 4 Н,
1/2
СН2СН2,  = 10 Hz). 13C NMR, : 133.3 (dddd, PC, Ph,
1/2
JP,C = 120.4 Hz, JP,C = 14.9 Hz, JP,C = 110.9 Hz, JP,C = 15.8 Hz);
131.8 (dd, oꢀС, Ph, JP,C = 4.3 Hz, JP,C = 4.6 Hz); 131.5 (s, pꢀPh);
128.2 (q, mꢀС, Ph, JP,C = 5.8 Hz); 65.2 (t, CH, JP,C = 63.2 Hz);
51.8 (s, NСН2); 24.8 (s, СН2СН2). Found (%): С, 70.44; Н, 6.15;

Polyfunctionalized methylphosphine oxides
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
385
PhP); 7.36—7.28 (m, 2 Н, oꢀH, PhN); 7.18—7.16 (m, 1 Н, pꢀH,
PhN). Found (%): С, 70.95; Н, 5.01; N, 4.39; Р, 9.55. С19Н16NРО2.
Calculated (%): С, 71.02; Н, 5.02; N, 4.36; Р, 9.64.
A. B. Reitz, Chem. Rev., 1989, 89, 863; (e) H. E. Zinneman,
M. R. Baker, R. C. Bottner, M. M. Morrisey, S. Murphy,
J. Am. Chem. Soc., 1993, 115, 253.
Diphenyl(N,Nꢀdiethylaminomethyl)phosphine oxide (21).
Bis(N,Nꢀdiethylamino)methane (17) (0.53 g, 3.4 mmol) was addꢀ
ed with stirring to a suspension of 4a (0.5 g, 1.7 mmol) in benꢀ
zene (5 mL). The reaction mixture was warmed to 40 С, after which
a system of two immiscible liquid phases was formed. The system
was stirred for 2 h at 20 С, then diluted with CH2Cl2 (10 mL)
and washed with water (4×5 mL). The organic layer was separatꢀ
ed and dried with K2CO3. The drying agent was filtered off and
washed with CH2Cl2 (2×5 mL), the filtrate was concentrated to
a volume of ~2 mL, and hexane (8 mL) was added. The precipiꢀ
tate formed was doubly reprecipitated with hexane from a solution
in benzene. Compound 21 was obtained as a white crystalline
substance in a yield of 0.23 g (46%), m.p. 88—90 С (cf. Ref. 13:
m.p. 89—90 С). 31Р{1H} NMR, : 27.5 (s). 1Н NMR, :
7.84—7.77 (m, 4 H, oꢀH, Ph); 7.50—7.41 (m, 6 H, mꢀH, pꢀH,
Ph); 3.29 (d, 2 H, PCH2,2JP,H = 7.0 Hz); 2.63 (q, 4 H,
3. (a) F. Reck, S. Marmor, S. Fisherb, M. A. Wuonolaa, Bioorg.
Med. Chem. Lett., 2001, 11, 1451; (b) C. Alstermark, K. Amin,
S. R. Dinn, T. Elebring, O. Fjellstrom, K. Fitzpatrick, W. B.
Geiss, J. Gottfries, P. R. Guzzo, J. P. Harding, A. Holmén,
M. Kothare, A. Lehmann, J. P. Mattsson, K. Nilsson,
G. Sundén, M. Swanson, S. von Unge, A. M. Woo, M. J. Wyle,
X. Zheng, J. Med. Chem., 2008, 51, 4315; (c) L. Coudray, A. F.
Pennebaker, J.ꢀL. Montchamp, Bioorg. Med. Chem. Lett.,
2009, 17, 7680; (d) L. Coudray, J.ꢀL. Montchamp, Eur. J.
Org. Chem., 2009, 27, 4646; (e) C. Fougere, E. Guenin,
J. Hardouin, M. Lecouvey, Eur. J. Org. Chem., 2009, 34, 6048.
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Hall, L Maier, D. Strub, V. Melillo, P. A. Baumann,
R. Bernasconi, C. Gentsch, K. Hauser, J. Jaekel, G. Karlsꢀ
son, K. Klebs, L. Máitre, C. Marescaux, M. F. Pozza,
M. Schmutz, M. W. Steinmann, H. van Riezen, A. Vassout,
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Ed., 1997, 36, 253; (b) H. Monenschein, G. Drager, A. Jung,
A. Kirschning, Chem. — Eur. J., 1999, 5, 2270; (c) H. Monꢀ
enschein, M. Brunjes, A. Kirschning, Synlett, 2002, 3, 525;
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Eur. J. Org. Chem., 2004, 5, 1149; (e) A. Kirschning, C. Kujat,
S. Luiken, E. Schaumann, Eur. J. Org. Chem., 2007, 15, 2387.
6. (a) V. P. Morgalyuk, Abstr. 15th Intern. Conf. on Chemistry of
Phosphorus Compounds (ICCPСꢀXV), (St. Petersburg, Russia,
May 25—30, 2008), St. Petersburg, 2008, 183; (b) V. P. Morꢀ
galyuk, P. V. Petrovsky, K. A. Lyssenko, E. E. Nifant´ev,
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Bull., Int. Ed., 2009, 58, 248].
3
2 NCH2CH3, JH,H = 7.0 Hz); 0.88 (t, 6 H, 2 NCH2CH3,
3JH,H = 7.0 Hz). Found (%): С, 71,21; Н, 7.69; N, 4.77; Р, 10.77.
С17Н22NОР. Calculated (%): С, 71.10; Н, 7.72; N, 4.88;
Р, 10.78.
cisꢀBis(Pꢀhydroxydiphenylphosphine)palladium(II) chloride (22).
Compound 4a (0.57 g, 2 mmol) was added with stirring under
inert atmosphere at 20 С to a solution of PdCl2•(CH3CN)2 (18)
(0.25 g, 1 mmol) in CH2Cl2 (40 mL). A red solution was formed
within 20 min. The solution was stirred for 2 h and water
(22 mmol) was added. After stirring for 15 min, the organic layer
was separated and dried with MgSO4. The drying agent was
filtered off, the filtrate was washed with CH2Cl2 (4×5 mL), and
concentrated to a volume of ~3 mL. Benzene (15 mL) was addꢀ
ed. A dark red oil that formed was gradually dissolved for 3 days
at 20 С and a yellow crystalline precipitate was formed. The
filtrate was decanted, and the precipitate was washed by decanꢀ
tation with benzene (4×5 mL) and hexane (2×5 mL), dried
in vacuo (12 Torr), and reprecipitated with benzene from a soluꢀ
tion in CH2Cl2. After drying in vacuo (1 Torr), cisꢀbis(Pꢀhydrꢀ
oxydiphenylphosphine)palladium(II) chloride (22) was obtained
as a light yellow crystalline substance in a yield of 0.27 g (75%), m.p.
125—127 С (with decomp.). 31Р{1H} NMR, : 78.5 (s). 1Н NMR,
: 7.57—7.51 (m, 8 H, oꢀH, Ph); 7.40—7.35 (m, 4 H, pꢀH, Ph);
7.26—7.21 (m, 8 H, mꢀH, Ph); 5.29 (s, 2 H, OH). Found (%):
С, 49.28; Н, 3.83; Р, 10.61; Cl, 12.45. С24Н22Cl2О2P2Pd. Calꢀ
culated (%): С, 49.59; Н, 3.82; Р, 10.66; Cl, 12.20.
7. V. P. Morgalyuk, T. V. Strelkova, Zh. Obshch. Khim., 2011,
81, 1643 [Russ. J. Gen. Chem. (Engl. Transl.), 2011, 81, 2096].
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311, 577.
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193, 222.
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Received June 12, 2011;
in revised form October 11, 2011