Synthesis of organophosphorus compounds based on the reaction of elemental phosphorus with proton-donor reagents

Article abstract of DOI:10.1134/S1070363215020085

Reaction of elemental (white) phosphorus with proton-donor reagents has been studied. The following organophosphorus compounds containing P-O and P-S bonds have been synthesized: metal hypophosphites and phosphites, and ammonium salts of O,O′-diesters of dithiophosphoric, S,S′-diphenyldithiophosphoric, S,S′-dialkyltetrathiophosphoric, O,O′-alkylidenedithiophosphoric acids, and octathiotetraphosphetane. The reaction products include highly efficient inhibitors of steel corrosion with carbonic acid and hydrogen sulfide as well as compounds showing fungicide, anticancer, and anti-inflammatory activity.

Full text of DOI:10.1134/S1070363215020085

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 2, pp. 392–401. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © E.K. Badeeva, E.V. Platova, E.S. Batyeva, 2015, published in Zhurnal Obshchei Khimii, 2015, Vol. 85, No. 2, pp. 219–228.
To the 80th Anniversary of B.I. Ionin
Synthesis of Organophosphorus Compounds
Based on the Reaction of Elemental Phosphorus
with Proton-Donor Reagents
E. K. Badeeva, E. V. Platova, and E. S. Batyeva
Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, Tatarstan, 420088 Russia
email: ybadeev.61@mail.ru
Received September 22, 2014
Abstract—Reaction of elemental (white) phosphorus with proton-donor reagents has been studied. The
following organophosphorus compounds containing P–O and P–S bonds have been synthesized: metal
hypophosphites and phosphites, and ammonium salts of О,О'-diesters of dithiophosphoric, S,S'-diphenyl-
dithiophosphoric, S,S'-dialkyltetrathiophosphoric, О,О'-alkylidenedithiophosphoric acids, and octathiotetra-
phosphetane. The reaction products include highly efficient inhibitors of steel corrosion with carbonic acid and
hydrogen sulfide as well as compounds showing fungicide, anticancer, and anti-inflammatory activity.
Keywords: white phosphorus, amines, proton-donor reagent, hypophosphite, phosphite, corrosion inhibitor
DOI: 10.1134/S1070363215020085
Synthesis of organophosphorus compounds from
elemental phosphorus (majorly from its most reactive
form, white phosphorus) has drawn much attention due
to its simplicity and the possibility to convert the
element into a complex organophosphorus molecule in
a single step. Moreover, such an approach is ecolo-
gically friendly and economically sound because it
avoids formation of toxic and harmful side products:
hydrogen chloride and hydrogen sulfide.
salts of О,О'-diesters of dithiophosphoric, S,S'-di-
phenyldithiophosphoric, S,S'-dialkyltetrathiophosphoric,
О,О'-alkylidenedithiophosphoric acids, and octathio-
tetraphosphetane; some of the prepared compounds
possess practically useful properties [1–8]. This work
extends a series of studies of the reactions of white
phosphorus with proton-donor reagents; herein we
summarize the earlier obtained data and report on new
results.
We have elaborated the approach to prepare organo-
phosphorus compounds containing P–O and P–S
bonds directly from elemental (white) phosphorus by
selecting the appropriate proton-donor, nucleophilic,
and electrophilic reagents. Realization of this approach
opens a way to the synthesis of a variety of practically
useful compounds, such as reducing agents for
chemical nickel-plating of metals, antioxidants, vulcaniza-
tion activators, foam stabilizers, photoreagents, light-
and thermostabilizers, additives for lubricating oils,
corrosion and salt deposition inhibitors, drugs, etc.
Reaction of white phosphorus with aqueous solu-
tion of β-hydroxyethyltriethylammonium hydroxide
(choline). It is known that splitting of the P–P bonds of
P4 molecule tetrahedron by nucleophilic reagents (for
example, hydroxide anion) yields phosphide anion.
The latter, being a strong base, can further attack
neutral P4 molecule to stabilize the negative charge via
formation of oligomeric phosphides in the absence of
other electrophilic compounds. In the aqueous
medium, an unstable intermediate is formed, which is
slowly decomposed with evolution of hydrogen, phos-
phine, hypophosphite and phosphite ions [9].
Using the proposed approach, we have synthesized
different types of organophosphorus compounds: metal
hypophosphites and phosphites as well as ammonium
Earlier we have worked out, optimized and
industrially tested a general, ecologically friendly, and
392

SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS
393
Scheme 1.
P4 + 4[Me3NCH2CH2OH]OH_ + 4H2O
+
_
+
4[Me3NCH2CH2OH] OP(O)H2 + 2H2
P4 + 4Me3N + 4
+ 8H2O
I
O
Scheme 2.
_
[Me3NCH2CH2OH]_OP(O)H2 + NaOH
+
+
NaH2PO2 + [Me3NCH2CH2OH]OH
II
Scheme 3.
+
_
[Me3NCH2CH2OH]OH
P4 + 4H2O + 4M(OH)2
4MHPO3 + 6H2
MHPO3 + H2SO4
H3PO3 + MSO4
III
M = Ba, Ca.
practically feasible one-pot synthesis of phospho-
rus(III) acids and their derivatives: phosphites and
hypophosphites [1–5]. The method is based on the
reaction of white phosphorus with β-hydroxyl-
ethyltriethylammonium hydroxide (choline) either
introduced in the form of aqueous solution or formed
in situ from the precursors: trimethylamine, ethylene
oxide, and water. For example, the reaction under mild
conditions (50–80°С, 9–10 h) has afforded choline
hypophosphite I in up to 95% yield [1, 3] (Scheme 1).
hypophosphite (I) was tested as a reducing agent in
electrochemical nickel-plating industry [4].
Hydride shift in the reaction of white phos-
phorus with aqueous solution of choline. It is
reasonable to assume that generation of hydrogen in
the reaction of P4 with aqueous solution of choline
occurs via protonation of a P–H hydrogen atom of
some intermediate by water molecule, provided that
this hydrogen is partly negatively charged (hydride-
like) allowing for the hydride shift.
The reaction of choline hypophosphite I with
solution of NaOH in methanol has resulted in recovery
of choline and formation of sodium hypophosphite II
[2] (Scheme 2).
Hδ_
+ H2O
P+ + H2 + OH_
P
Mechanism of this process can involve the steps of
phosphide anion generation followed by protonation
with water and formation of four-phosphorus anions at
the second stage of P–P bond cleavage. The
competition between conventional protonation of the
phosphide phosphorus atom and protonation of the
hydride-like hydrogen atom to form hydrogen mole-
cule can favor the latter reaction; this has been
observed experimentally. The phosphide center is
strongly sterically hindered by choline residues,
blocking the interaction with the water molecule.
Apparently, attraction of cationic sites of two choline
residues to the phosphide group strongly contributes to
the above-mentioned steric shielding and causes the
special behavior of choline in the reaction with white
phosphorus as compared to other nucleophiles
(Scheme 4).
Under conditions of competitive formation of
hypophosphite and phosphite structures, formation of
the latter is known to be favorable in strongly alkaline
media. The reaction of white phosphorus with choline
and water in the presence of alkali earth metal
hydroxides Ва(ОН)2 or Са(ОН)2 has allowed obtaining
phosphorous acid III in high yield [5] (Scheme 3).
Preparation of hypophosphites and phosphites via
the proposed method is not accompanied by formation
of toxic phosphine; the process is wasteless (because
of full conversion of phosphorus) and recyclable (the
formed choline can be recovered). Hence, this method
to prepare hypophosphites and phosphites in high yield
in a single stage starting from elemental phosphorus is
technologically and economically sound. Choline
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

394
BADEEVA et al.
Scheme 4.
+
R = (CH2)2NMe3
RO
RO
P_
P
H
P
P
P
H2O
RO_ + P4
P
P
_OH _
P
_
_
RO
RO
RO
RO
P_
P
P
P
OR
P
P
P
PH_
H
RO
H2
_OH_
+H2O
RO
RO
P
OR
_
_
P
OR
RO
OH
P
ROP(O)H2
HOP(O)H2
P
P
+
P
H
O
P_
H
+
(CH3)NCH2CH2OH_OP(O)H2
ROP(O)H2 + HOP(O)H2 + H2
I
Scheme 5.
+
O
NHR2
CHR'
OH
_
O
R2NH + R'CHO + (HO)2P(O)H
HO
+
H3PO4 R2NCH2R'
P
H
IV
R = Et, _(CH2CH2OCH2CH2)_, R' = H, Ph.
The choline salt of hypophosphorous acid I is
to undergo hydride shift has been demonstrated in the
case of secondary amine–aldehyde–phosphorous acid
system. The only product of the reaction at 60–100°С
is the corresponding tertiary ammonium phosphate IV.
After treatment of the obtained salts with alkali, the
corresponding tertiary amines have been isolated,
whose structures have been confirmed by a com-
bination of physico-chemical methods and elemental
analysis (Scheme 5).
formed both via hydrolysis of the choline ester of the
acid and via neutralization of free acid H2P(O)OH with
choline [10].
When trimethylammonium cation in choline is
replaced by other ammonium radicals R3N+ (R = Et,
Bu, or PhCH2Me2) the shielding of phosphide center is
so strong that the interaction of water with the hydride-
like hydrogen becomes impossible, and the reaction
follows another ways leading, in particular, to
evolution of phosphine [11].
The reactions with di- and monosodium salts of
phosphorous and hypophosphorous acids proceed
similarly, yielding corresponding sodium salts of phos-
phoric acid and tertiary amines (Scheme 6).
Hydride shift in the amine–aldehyde–phos-
phorous acid system. The ability of the Р–Н fragment
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SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS
395
Scheme 6.
O
O
P
(NaO)2
NaO
(NaO)2
NaO
H + Et2NH + CH2O
OH + Et2NMe
P
O
O
OH
OH
+ Et2NH + CH2O
+ Et2NMe
P
P
H
OH
O
P
O
P
H
OH
OH
NaO
+ 2Et2NH + 2CH2O
NaO
+ 2Et2NMe
H+
Scheme 7.
Et2N CH2 OH + НХ
Et2NH HХ + СH2O
V_ХI
[Et2N
=
CH2]+ Х_ + H2O
NH2Et2Х + CH2O + H3PO3
a
b
Et2NMe H3PO4
P(O)(OH)2 + HХ + H2O
ХIII
Et2NCH2
ХII
HX = HCl (V), 0.5H2SO4 (VI), H2SO4 (VII), MeC6H4SO2OH (VIII), CF3COOH (IX), H3PO3 (X), MeCOOH (XI).
This reaction represents reductive alkylation of
secondary amines with aldehydes [12] in the presence
of the hydrogenating agent: phosphite or hypophos-
phite ion.
It has been shown that in the case of diethyl-
ammonium salts of weak acids X and XI the main
process is oxidation of the phosphite anion into
phosphate anion via hydride shift of hydrogen from
phosphorus to the positively charged carbon atom of α-
hydroxyalkylammonium cation to form salts of
phosphoric acid XII (Scheme 7, route a), whereas for
salts of stronger acids V–IX aminomethylation of the
phosphorous acid leading to aminomethylphosphonous
acid XIII predominates (Scheme 7, route b).
The reaction of phosphorous acid with aqueous
solution of formaldehyde in the presence of various
diethylammonium salts V–XI has been studied by 31Р
NMR spectroscopy and the conditions favoring the
hydride shift have been elucidated.
The oxymethyl derivative is formed in the reaction
of salts V–XI with formaldehyde and free acid HX is
simultaneously released, the latter determining рН of
the reaction medium and concentration of the immo-
nium cation. As basicity of the nitrogen atom in
Et2NHCH2OH is strongly lowered due to conjugation
of its lone-electron pair with the σ* orbital of the
С–ОН bond [13, 14], НХ acid exists in the free form.
In the diethylamine salt–formaldehyde–phosphorous
acid system, two competitive processes can occur:
phosphonaminoalkylation (Scheme 7, route a) and
redox reaction (Scheme 7, route b), the predominant
pathway being determined by pH of the medium
(Scheme 7).
Reaction in the Р4–ROН–amine–sulfur system.
Extending our studies on the methods to synthesize
organophosphorus compounds starting from elemental
phosphorus, we trialed the following combination of
reagents: white phosphorus–proton donor–the con-
jugate base–the fourth reagent. Alcohols and phenols
acted as proton donors. We anticipated that addition of
an electrophilic reagent efficiently competing with
protonation of the phosphide intermediate (result of the
above-discussed P–P bond splitting in P4) by the
nucleophile or rapidly reacting with the Р–Н bond
could enhance selectivity of the target product
formation in the studied system.
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BADEEVA et al.
Taking the white phosphorus–PhOH–PhONa–CCl4
system as an example, we determined the range of
phenols pKa allowing their reaction with Р4 to obtain
4.6), the corresponding salt of diethyldithiophosphoric
acid was not obtained even after 30 h heating, the
conversion of phosphorus being of 15%.
triarylphosphites
[15].
Application
of
N-
The elaborated one-pot method of ammonium salts
of О,О'-diesters of dithiophosphoric acids XIV
preparation is practically feasible and (unlike the
industrial method of dialkyl- and diaryldithio-
phosphoric acids preparation via reaction of phos-
phorus pentasulfide with alcohols or phenols) does not
result in evolution of hydrogen sulfide. The reaction
can be carried out in toluene solution or in bulk.
Ammonium salts of О,О'-diesters of dithiophosphoric
acids XIV are obtained in 70–98% yield as crystalline
compounds or viscous liquids. Their structure has been
alkoxymethyldialkylamines and their heterocyclic
analogs (piperidine and morpholine) in the white
phosphorus–alcohol–sodium alkoxide system led to
formation
of
a
mixture
of
esters
of
aminomethylphosphonic and aminomethylphosphinic
acids [16].
Using elemental sulfur was recognized as the best
approach to prepare phosphorus-sulfur-containing
compounds. In particular, convenient and highly
selective synthesis of ammonium salts of О,О'-diesters
of dithiophosphoric acids XIV was elaborated basing
on cascade reactions in the white phosphorus–alcohol
(phenol)–amine–elemental sulfur system [6, 17].
1
confirmed by Н, 31Р NMR (δР 108–115 ppm), and IR
spectroscopy; the composition has been proved by
elemental analysis.
According to conventional mechanism of white
phosphorus reactions with nucleophiles in proton-
donor media, the opening of P4 tetrahedron is followed
by protonation of the phosphide center with alcohol to
form a compound containing Р–Н bond and another
nucleophile, RO–. The presence of active sulfur
capable of reacting with Р–Р, РН, or РН2 fragments
favored formation of more stable intermediates with
Р=S and Р(S)SН fragments. Repetition of the
described stages finally led to ammonium salts of
О,О'-diesters of dithiophosphoric acids, valuable organo-
phosphorus products.
When the reaction of white phosphorus and sulfur
with p-cresol was performed in the presence of mor-
pholine or pyridine in DMF, dimethylammonium salt
of di(p-methylphenyl)dithiophosphoric acid XV was
isolated, apparently formed via oxidative hydrolytic
degradation of DMF in the presence of bases with
elimination of dimethylamine.
P4 + S8 + n-MeC6H4OH
DMF
(p-MeC6H4O)2P(S)SH·HNMe2.
XV
P4 + S8 + 8ROH + 4R1NR22 → 4(RO)2PSH·R1NR22 + 2H2,
The use of the R2NCH2NR2 bisamines at the Р4–S8–
i-BuОН–R2NCH2NR2 ratio of 1 : 2 : 2.2 : 0.5 allowed
preparation of the corresponding bissalts XVI.
XIV
R = Et, i-Pr, i-Oct, C12H25, C12–14H25–29, Ph, p-MeC6H4,
p-C9H19C6H4; R1 = R2 = H; R1 = R2 = Et; R1 = R2 = Bu; R1 =
C12H25, R2 = H; R1 = Ph, R2 = Me; R1 = C25H51, R2 = H;
R1 = C12–14H25–29, R2 = Me; R1 = H, R2 = (–CH2–)5; R1 =
R2 = (–CH–)5; R1 = CH2NEt2, R2 = Et2; R1 = i-PrOCH2, R2 =
S
||
S
||
(i-BuO)2P–SH·R2NCH2NR2·HS–P(OBu-i)2,
Et2; R1 = CH2N(–CH2–)5, R2 = (–CH2–)5; R1 = R2
=
XVI
CH2CH2OH; R1 = H, R2 = CH2CH2OH; R1 = CH2CH2OH,
R2 = H.
R = Et, (–CH2–)5.
A wide range of aliphatic alcohols was introduced
into the reaction in combination with ammonia,
primary, secondary, tertiary aliphatic, aromatic, and
heterocyclic amines as well as ethanolamines as the
amine component. The reaction proceeded in the
presence of amines with рKа of 8.8 to 11.2. However,
even when using less basic amines, like pyridine (рKа
5.23) or N,N'-dimethylaniline (рKа 5.06), the cor-
responding salts could be isolated. With aniline (рK
N-Alkoxymethyldialkylamines were used as well
for activation of sulfur; these amines are known for
high reactivity and ability to eliminate an alkoxy anion
[13]. Heating of white phosphorus with isopropanol,
sulfur, and diethyl(isopropoxymethyl) amine XVII at
80–85°С resulted in diethylamine salt of diisopropyl-
dithiophosphoric acid, due to hydrolysis of the initially
formed immonium salt to yield the carbonyl compound
and the secondary amine salt XVIII [17] (Scheme 8).
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SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS
397
Scheme 8.
S
(i-PrO)2P
P4 + S8 + i-PrOH + i-PrOCH2NEt2
ХVII
[Et2N
CH2 OPr-i]
SH
S
S
HOH
+
(i-PrO)2P
(i-PrO)2P
[Et2N
HNEt2 + H2C
CH2]
O
S_
_i-PrOH
SH
ХVIII
Salts of higher (С12–С14) dialkyldithiophosphoric
acids XIV were obtained via reesterification of salts of
lower (diisopropyl- or diisobutyldithiophosphoric)
acids in the presence of acidic catalysts.
Reaction in the Р4–RSН–amine–sulfur system.
Replacement of alcohol with thiol in the white
phosphorus–alcohol–amine–sulfur system affected the
reaction course [22]. For instance, with isobutyl- or
isopentylthiol XIX, two phosphorus-containing
products XIX and XX were isolated. Four-membered
monocyclic phosphorus derivatives, ammonium salts
of 1,2,3,4-tetramercapto-1,2,3,4-tetrathioxotetraphos-
phetane XXI were obtained as minor products in 10–
18% yield along with the major reaction product:
ammonium salts of S,S'-dialkyltetrathiophosphoric
acids (XX) (yield 78–80%) [8, 22–24]. The structure
of the obtained salts was elucidated by a set of
physico-chemical methods and (for selected products)
additionally confirmed by X-ray diffraction analysis
[22–24] (Scheme 9).
A series of the obtained ammonium salts of О,О'-
dialkyldithiophosphoric acids XIV was examined as
inhibitors of acidic corrosion of steel [19–21]. Among
a variety of available inhibitors, these efficiently protect-
ing steel in the media containing hydrogen sulfide or
carbon dioxide are very limited; hence, elaboration of
new efficient and universal inhibitors of steel corrosion
is still a topical problem. We have found that ammo-
nium salts of О,О'-dialkyldithiophosphoric acids ob-
tained basing on the industrially available alcohols
(i-С8Н17ОН, i-С12–14H25–29ОН) and amines (Et3N,
Et2NС12–14H25–29) are more efficient inhibitors of steel
corrosion induced by carbonic acid and hydrogen
sulfide as compared with the known Russian and
foreign inhibitors. The figure displays representative
samples of steel plates used in the test of triethylammo-
nium salt of О,О'-diisooctyldithiophosphoric acid XIV
as inhibitor of carbonic acid corrosion. The advantage
of the obtained inhibitors is the enhanced protective
efficiency with increasing medium temperature (30–
80°С). Operation at elevated temperature is of special
importance for oil extraction from deep strata [19].
When aliphatic thiols were replaced by thiophenol,
a hardly separable mixture of phosphorus-sulfur-
containing products was obtained. In the absence of
sulfur, the salts of S,S'-diesters of phosphoric acid were
formed [7, 25].
Using triethylamine as an example, the possibility
of ammonium salts of S,S'-diphenyldithiophosphoric
acid XXII preparation via reaction of white phos-
phorus with thiophenol in the presence of air oxygen
was demonstrated (Scheme 10).
(b)
(a)
(c)
20 μm
20 μm
20 μm
Soft steel plates: (а) pristine; (b) after 22 h incubation in corrosive medium; (c) after 22 h incubation in corrosive medium in the
presence of 1 mg/L of salt XIV.
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398
BADEEVA et al.
Scheme 9.
S
P
P
S
S
P
P
S
R1NR22 HS
R1NR22 HS
SH R1NR22
SH R1NR22
P4 + RSH + R1NR22 + S8
(RS)2P(S)SH NR1R22
+
ХIХ
ХХ
ХХI
R = Bu, i-Am; R1 = R2 = Et; R1 = H, R2 = (CH2)4; R1 = Me, R2 = (CH2CH2)2O; R1 = H, R2 = Et; R1 = H, R2 = (CH2)5.
Scheme 10.
O2
P4 + PhSH + Et3N
P4 + PhSH + Et3NH
(PhS)2P(O)OH NEt3 + (PhS)2
MeCN
ХХII
O2
MeCN
(PhS)2P(O)OH HN
C
Me + (PhS)2
NEt2
ХХII
Scheme 11.
S
P
P
S
S
P
P
S
R1NR22 HS
R1NR22 HS
SH R1NR22
SH R1NR22
P4 + S8 + HOCH2CH2CH2OH + R1NR22
ХХI
R1 = R2 = Et; R1 = H, R2 = –(CH2)5–; R1 = H, R2 = Et; R1 = Me, R2 = (CH2CH2)2O; R1 = CH2C6H5, R2 = Me.
In the case of diethylamine, when the reaction was
80°C during 8–10 h. The reaction proceeded with full
conversion of white phosphorus and was not accom-
panied by evolution of hydrogen sulfide. After com-
pletion of the reaction and cooling the mixture,
compounds with the 31P NMR spectra signal at δP 120–
122 ppm were isolated, corresponding to ammonium
salts of octathiotetraphosphetane XXI [28]. Physico-
chemical and spectral parameters of salts XXI fully
coincided with those for the compounds obtained via
reaction of Р4, sulfur, and amines in the presence of
thiols, which were earlier studied using IR/Raman, 31Р,
carried out in acetonitrile medium, the N,N'-
diethylacetamidinium salt of S,S'-diphenyldithio-
phosphoric acid XXIII has been obtained. Formation
of amidine likely occured via the reaction of aceto-
nitrile with thiophenol in the presence of amines
leading to thioimidate, followed by nucleophilic sub-
stitution of thiophenol residue in the latter by amines
to yield N,N'-diethylacetamidine. (The formation of
thioiminoesters via reaction of thiols with nitriles and
their application in synthesis of amidines has been
discussed earlier [26, 27]). The structure of salt XXIII
was confirmed by X-ray diffraction analysis [7].
1
and Н NMR spectroscopy as well as theoretically by
DFT method [8, 23, 24].
Reaction in the Р4–alkylene glycol–amine–sulfur
system. Extending the study of white phosphorus
reaction with proton-donor reagents, the reactions of P4
with alkylene glycols were studied in the same system
(Scheme 11).
To summarize, octathiotetraphosphetane deriva-
tives were obtained via reaction of white phosphorus,
sulfur, and amines both with aliphatic thiols and with
alkylene glycols. The latter method was obviously
more handy and preferable, since application of readily
available and ecologically friendly 1,3-propylene
glycol avoided use of toxic thiols.
The reaction in the Р4–1,3-propylene glycol–
amine–S8 system was performed in acetonitrile at 65–
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SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS
399
Octathiotetraphosphetane salts XXI bearing dif-
ferent functional groups are of interest in view of many
applications, including medicine and biology. These
compounds form metal complexes with transition
metal halogenides of groups I and VIII: Cu(I), Cu(II),
Ag(I), Au(I), Fe(II), and Co(II). In cooperation with
the research group from New-Mexico-Tech University
(USA), the octathiotetraphosphetane salts were tested
for bactericide, fungicide, anticancer, and anti-
inflammatory activity. For ammonium salts of
octathiotetraphosphetane and the metal derivatives, the
fungicide (Candida albicans), anticancer (HeLa), and
anti-inflammatory activity was revealed, depending on
the nature of the metal or amine [27].
diethylamine, and the mixture was self-heated to 50°С.
The reaction mixture was cooled to room temperature
and then heated to 90°С. The formed precipitate was
filtered off and washed with acetone to give 9.6 g
(80%) of Na2HPO4. 31Р NMR spectrum, δР, ppm: 4.
Found, %: Н 0.84; Р 22.21. HNa2O4P. Calculated, %:
Н 0.70; Р 21.83.
Reaction of monosodium salt of phosphorous
acid with diethylamine and formaldehyde. Similarly,
10.2 g (85%) of NaH2PO4 was obtained from 10.4 g of
NаН2РО3, 10.1 mL of diethylamine and 3.24 mL of
41% formaldehyde solution. 31Р NMR spectrum, δР,
ppm: 4.1. Found, %: Н 1.68; Р 26.03. H2NaO4P.
Calculated, %: Н 1.67; Р 25.84.
Our systematic study of the reactions of white
phosphorus with proton-donor reagents allowed to
work out and to optimize highly selective and
ecologically friendly methods for preparation of
valuable organophosphorus products directly from
elemental phosphorus, avoiding evolution of hydrogen
sulfide and/or phosphine.
Reaction of phosphorous acid with morpholine
and benzaldehyde. 8.7 g (0.1 mol) of morpholine was
added at stirring to 8.2 g (0.1 mol) of phosphorous
acid, the mixture was self-heated to 95°С. 10.18 mL
(0.1 mol) of benzaldehyde was added dropwise to the
obtained mixture, and the mixture was heated at 95–
150°С during 1.5 h. 23.5 g (85%) of benzylmorpholine
phosphate glassy mass was obtained. 31Р NMR spec-
trum, δР, ppm: 4.2. The obtained salt was dissolved in
water, added dropwise to 24 g of NaOH under the
layer of diethyl ether, and stirred at 35–40°С during
3.5 h. The formed Na3PO4 precipitate was filtered off
and washed with diethyl ether (3 × 50 mL); ethereal
extracts were combined with the filtrate, the solvent
was removed, and the residue was distilled to obtain
12 g (79%) of benzylmorpholine, bp 124–125°C; nD20
EXPERIMENTAL
IR spectra were recorded with a Tensor 27 (Bruker)
1
Fourier spectrometer in KBr at 4000–400 cm–1. Н
NMR spectra were registered using a Bruker MSL-500
(500.13 MHz) spectrometer with residual protons of
the deuterated solvent as reference. 31P NMR spectra
were recorded with a Bruker MSL-400 (161.97 MHz)
spectrometer, the internal references being TMS for
(1Н) and 85% Н3РО4 (31Р). C, H, N, and S elemental
analysis was performed with a CHN-3 analyzer,
content of phosphorus was determined via standard
pyrolysis method.
1
1.5257. H NMR spectrum (ССl4), δ, ppm: 2.2–2.4 m
(4Н, СН2ОСН2), 3.46–3.6 m (4Н, СН2NСН2), 3.3 s
(2Н, СН2N), 7.1 s (5Н, С6Н5). Found, %: С 74.12; Н
8.06; N 8.32. C11H15NO. Calculated, %: С 74.57; Н
8.47; N 7.91.
Reaction of sodium hypophosphite with diethyl-
amine and formaldehyde. 20.6 mL of diethylamine
was added dropwise to 13.1 mL of 41% solution of
formaldehyde at cooling (≤30°С). 10.6 g of NаН2РО2
was added to the obtained methylol derivative, and the
reaction mixture was heated at 90–95°С during 10 h.
The formed precipitate was filtered off and washed
with acetone to give 11.9 g (82%) of NaH2PO4. 31Р
NMR spectrum, δР, ppm: 4.1. Found, %: Н 1.91; Р
26.14. H2NaO4P. Calculated, %: Н 1.67; Р 25.83.
Reaction of phosphorous acid with morpholine
and formaldehyde. 6.55 mL (0.1 mol) of 41%
aqueous solution of formaldehyde was added dropwise
to 8.7 g (0.1 mol) of morpholine. 8.2 g (0.1 mol) of
phosphorous acid was then added, and the mixture was
stirred during 0.5 h at 85–95°С. After removal of water
16.6 g (83%) of methylmorpholine phosphate viscous
mass was isolated. 31Р NMR spectrum, δР, ppm: 4.2.
Solution of 16.6 g of methylmorpholine phosphate in
10 mL of water was added dropwise to 12 g of NaOH
in diethyl ether, and the mixture was incubated at 40°С
during 3.5 h. The formed precipitate of Na3PO4 was
filtered off and washed with ether (3 × 30 mL);
ethereal extracts and filtrate were combined, ether was
Reaction of disodium salt of phosphorous acid
with diethylamine and formaldehyde. 27 mL of 41%
formaldehyde solution was added dropwise to a
mixture of 12.6 g disodium phosphite and 10.3 mL of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

400
BADEEVA et al.
removed, and the residue was distilled to give 6.7 g
(80%) of methylmorpholine; bp 116–117°C, nD20
1.4325. Found, %: С 59.82; Н 10.61, N 14.02. C5H11NO.
Calculated, %: С 59.40; Н 10.89, N 13.86.
O4P2S4. Calculated, %: С 48.65; Н 9.01; N 4.20; Р
9.31; S 19.22.
Synthesis of dimethylammonium salt of di(p-
tolyl)dithiophosphoric acid. а. Mixture of 1.8 g
(58 mmol) of Р4, 3.6 g (112.5 mmol) of sulfur, 12.6 g
(117 mmol) of p-cresol, 5.6 g (64 mmol) of mor-
pholine, and 2.4 g (33 mol) of DMF was heated during
4 h at 60°С, during 5 h at 80–90°С, and during 5 h at
100–120°С. Excess of СН3СN was added to the
reaction mixture. 8.2 g (70% with respect to DMF) of
transparent crystals of dimethylammonium salt of di(p-
tolyl)dithiophosphoric acid precipitated upon cooling,
mp 146–147°С (СН3СN). IR spectrum, ν, cm–1: 680,
Similarly, the reactions of phosphorous acid with
diethylamine were performed in the presence of
formaldehyde or benzaldehyde. 16.5 g (82.5%) of
methyldiethylamine phosphate and 22.3 g (85.2%) of
benzyldiethylamine phosphate, respectively, was
isolated.
Reaction of phosphorous acid with diethylamine
salts V–XI and formaldehyde. 6.38 mL of 41%
aqueous solution of formaldehyde and 7.97 g of
phosphorous acid were sequentially added to 50 mL of
1.94 mol/L solution of diethylamine salt V–XI. The
reaction mixture was heated during 2 h at 80–100°С,
water was removed; the viscous residue was
sequentially washed with ether and acetone, and then
incubated in vacuum. The products were analyzed
using 31Р NMR spectroscopy.
1
700 (Р=S), 1600 (Р–О–Аr), 2420, 2780 (S–Н). Н
NMR spectrum (СD3СN), δ, ppm: 2.3 s (6Н,
CН3C6Н4О), 2.6 s [6H, (CН3)2N], 7.13 s (8Н, C6Н4О).
31Р NMR spectrum, δР, ppm: 108. Found, %: С 54.48;
Н 6.20; N 3.88; Р 9.24; S 17.65. С16Н22NO2PS2.
Calculated, %: С 54.08; Н 6.19; N 3.94; Р 8.73; S
18.03.
b. Mixture of 2 g (64.5 mmol) of Р4, 4 g (115 mmol)
of sulfur, 14 g (130 mmol) of p-cresol, 3 g (38 mmol)
of pyridine, and 2 g (27 mmol) of DMF was heated
during 10 h at 70–80°С and during 14 h at 90–120°С.
After addition of acetonitrile, 0.4 g of unreacted sulfur
was precipitated. 31Р NMR spectrum, δP, ppm: 108.6
(40), 50.2 (19.5), –16.44 (40.5). Low-boiling petro-
leum ether was added to the filtrate. After 2 days
incubation, the lower layer crystallized to give 5.1 g
(53% with respect to DMF) of dimethylammonium salt
of di(p-tolyl)dithiophosphoric acid, mp 147–148°С
(СН3СN). IR spectrum, ν, cm–1: 680, 700 (Р=S), 1600
(Р–О–Аr), 2420, 2780 (S–Н). 1Н NMR spectrum
(СD3СN), δ, ppm: 2.3 s (6Н, CН3C6Н4О), 2.6 s [6H,
Synthesis of diethylbisamine salt of diisobutyldi-
thiophosphoric acid. Mixture of 1 g (32 mmol) of Р4,
2.2 g (69 mmol) of sulfur, 7.15 g (96 mmol) of
isobutanol, and 2.5 g (16 mmol) of diethylbisamine
was heated during 5 h at 70°С and during 6 h at 110–
115°С. The excess of alcohol was removed in vacuum.
The precipitated crystals of diethylbisamine salt of
diisobutyldithiophosphoric acid were separated by
filtration and washed with low-boiling petroleum
1
ether. Yield 9.2 g (89%), mp 86–87°С. Н NMR
spectrum (С6D6), δ, ppm (J, Hz): 0.6 d [24Н, (СН3)2, J
6 Hz], 0.9 t (12H, CH3СН2, J 14 Hz), 1.36–1.9 m (4H,
CH), 2.4 q (8Н, СН3СН2), 3.5–3.8 (10Н, СН2О and
NСН2N). 31Р NMR spectrum, δР, ppm: 113. Found, %:
С 47.16; Н 9.75; N 3.89; Р 9.15; S 20.53.
С25Н60N2O4P2S4. Calculated, %: С 46.72; Н 9.34; N
4.36; Р 9.65; S 19.93.
31
(CН3)2N], 7.13 s (8Н, C6Н4О). Р NMR spectrum, δP,
ppm: 108. Found, %: С 53.62; Н 6.20; N 4.17; Р 9.03;
S 17.65. С16Н22NO2PS2. Calculated, %: С 54.08; Н
6.19; N 3.94; Р 8.73; S 18.03.
Synthesis of dipiperidinebisamine salt of diiso-
butyldithiophosphoric acid. Similarly, 8.3 g (78%) of
dipiperidinebisamine salt of diisobutyldithiophos-
phoric acid was obtained (mp 94–95°С) from 1 g
(32 mmol) of Р4, 2.2 g (69 mmol) of sulfur, 7.15 g
(96 mmol) of isobutanol, and 2.9 g (16 mmol) of
piperidinebisamine. 1Н NMR spectrum (С6D6), δ, ppm
(J, Hz): 0.66 d [24Н, (СН3)2, J 6 Hz], 0.83–1.33 m
(12H, CH2СН2СН2), 1.4–1.9 m (4H, CH), 2.53–2.88 m
(8Н, СН2NСН2), 3.5–3.78 m (10Н, NCH2N and
СН2О). 31Р NMR spectrum, δР, ppm: 111. Found, %: С
48.33; Н 9.46; N 4.15; Р 8.96; S 19.69. С27Н60N2·
Synthesis of diethylammonium salt of diiso-
propyldithiophosphoric acid (XVIII). Mixture of 1 g
(32 mmol) of Р4, 2 g (62 mmol) of sulfur, 5 g (35 mmol)
of diethyl(isopropoxymethyl) amine, and 10 mL of
isopropanol was heated during 0.5 h at 40–50°С and
during 20 h at 80–85°С; the mixture was evaporated
under water-jet pump vacuum, and petroleum ether
was added. The reaction mixture was crystallized to
give 7.2 g (78%) of diethylammonium salt of diiso-
propyldithiophosphoric acid XVIII, mp 92–93°С
1
(ether). IR spectrum, ν, cm–1: 640 (Р=S). Н NMR
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS
401
14. Comprehensive Organic Chemistry, Barton, D. and
Olli, W.D., Eds., Pergamon Press, 1979, vol. 3.
15. Ivanov, B.E., Badeeva, E.K., and Krokhina, S.S., Bull.
Acad. Sci. USSR, Chem. Sci., 1988, vol. 37, no. 11,
p. 2371.
16. Badeeva, E.K., Krochina, S.S., and Ivanov, B.E., Russ.
J. Gen. Chem., 2003, vol. 73, no. 9, p. 1376. DOI:
10.1023/B:RUGC.0000015981.21117.9f.
spectrum (СD3СN), δ, ppm (J, Hz): 1.23 d (12Н, СН3,
J 6.23 Hz), 1.33 t (6Н, СН3СН2, J 7.1 Hz), 3.04–3.13
m (4Н, СН2N+), 4.6–4.71 m (2H, CH). 31Р NMR
spectrum, δP, ppm: 115. Found, %: С 41.96; Н 9.53; N
4.83; Р 10.3; S 22.5. С10Н26NO2PS2. Calculated, %: С
41.81; Н 9.06; N 4.88; Р 10.8; S 22.29.
ACKNOWLEDGMENTS
17. Sinyashin, O.G., Batyeva, E.S., Ugryumov, O.V.,
Nizamov, I.S., Varnavskaya, O.A., Vasyukov, S.I.,
Khodyrev, Yu.P., Platova, E.V., Badeeva, E.K., and
Kursheva, L.I., Phosphorus, Sulfur, and Silicon, and the
Relat. Elem., 2013, vol. 188, nos. 1–3, p. 21. DOI:
10.1080/10426507.2012.740698.
18. Bohme, H. and Viehe, H.G., Iminium Salts in Organic
Chemistry. Part 1. Advances in Organic Chemistry:
Methods and Results, Taylor, E.C., Ed., New York:
John Willey and Sons, 1960.
This work was financially supported by Russian
Foundation for Basic Research (project 12-03-00479).
REFERENCES
1. Ivanov, B.E., Krokhina, S.S., Fridland, N.S., Plato-
va, E.V., Badeeva, E.K., Loskutov, L.G., Kluev, B.P.,
Mitrokhin, A.M., Beskopyl’nyi, A.M., and Kalashni-
kov, I.V., Author’s Certificate no. 1594950, 1989,
Byull. Izobret., 1996, no. 3.
2. Ivanov, B.E., Krokhina, S.S., Fridland, N.S., Plato-
va, E.V., Badeeva, E.K., and Beskopyl’nyi, A.M.,
Author’s Certificate no. 1616037, 1989, Byull. Izobret.,
1996, no. 3.
3. Ivanov, B.E., Krokhina, S.S., Fridland, N.S., Plato-
va, E.V., Badeeva, E.K., Loskutov, L.G., Kluev, B.P.,
Mitrokhin, A.M., Beskopyl’nyi, A.M., and Kalashni-
kov, I.V., Author’s Certificate no. 1616036, 1989,
Byull. Izobret., 1996, no. 2.
19. Badeeva, E.K., Batyeva, E.S., Platova, E.V., Khody-
rev, Yu.P., and Sinyashin, O.G., RF Patent 2400564,
publ. 27.09.2010, Byull. Izobret., 2010, no. 27.
20. Khodyrev, Yu.P., Platova, E.V., Tiwari, L., Batyeva, E.S.,
and Sinyashin, O.G., Corrosion Sci., 2011, no. 53, p. 976.
21. Batyeva, E.S., Ugryumov, O.V., Varnavskaya О.А.,
Khodyrev, Yu.P., Platova, E.V., Badeeva, E.K.,
Vasyukov, S.I., and Sinyashin, O.G., Petroleum Chem.,
2013, vol. 53, no. 2, p. 139.
4. Ivanov, B.E., Krokhina, S.S., Fridland, N.S., Plato-
va, E.V., Badeeva, E.K., Liakumovich А.G., Frid-
man, B.S., Gamer, P.U., Rybka, V.Ya., Loskutov, L.G.,
Kluev, B.P., Mitrokhin, A.M., Beskopyl’nyi, A.M.,
Grunberg, Yu.A., and Kalashnikov, I.V., Author’s
Certificate no. 1614451, 1989, Byull. Izobret., 1996, no. 4.
5. RF Patent 2179152, 2000, Byull. Izobret., 2002, no. 4.
6. RF Patent 2136690, 1998, Byull. Izobret., 1999, no. 4.
7. Badeeva, E.K., Batyeva, E.S., Gubaidullin, A.T., Litvi-
nov, I.A., and Sinyashin, O.G., Russ. J. Gen. Chem.,
2005, vol. 75, no. 6, p. 835. DOI: 10.1007/s11176-005-
0329-4.
8. Batyeva, E.S., Badeeva, E.K., Platova, E.V., Kursheva, L.I.,
Zvereva, E.E., Vandyukov, A.E., Katsyuba, S.A.,
Kovalenko, V.I., and Sinyashin, O.G., Heteroatom
Chem., 2011, vol. 22, p. 24.
9. Brodskii, E.K., Blankshtein А.А., Ershov, V.A., and
Talanov, N.D., Pererabotka fosfora (Recycling of
Phosphorus), Leningrad: Khimiya, 1985.
22. Batyeva, E.S., Badeeva, E.K., Platova, E.V., Gu-
baidullin, A.T., Porch, N., Edwards, L., Malik, I.,
Frolova, L.V., Magedov, I.V., Rogelj, S., and Sinya-
shin, O.G., Heteroatom Chem., 2013, vol. 24, p. 163.
DOI: 10.1002/hc.21077.
23. Badeeva, E.K., Krivolapov, D.B., Gubaidullin, A.T.,
Litvinov, I.A., Batyeva, E.S., and Sinyashin, O.G.,
Mendeleev Commun., 2005, no. 15, p. 22. DOI:
10.1070/MC2005v015n01ABEH001996.
24. Gubaidullin, A.T., Badeeva, E.K., Krivolapov, D.B.,
Litvinov, I.A., Batyeva, E.S., and Sinyashin, O.G.,
J. Struct. Chem., 2007, vol. 48, no. 5, p. 954. DOI:
10.1007/s10947-007-0140-7.
25. Badeeva, E.K., Batyeva, E.S., and Sinyashin, O.G.,
Russ. J. Gen. Chem., 2002, vol. 72, no. 2, p. 319. DOI:
10.1023/A:1015410726630.
26. Granik, V.G., Russ. Chem. Rev., 1983, vol. 52, no. 4,
p. 377.
27. The Chemistry of the Tiol Group, Patai, S., Ed., London:
Wiley, 1974, pt. 2.
28. Badeeva, E.K., Platova, E.V., and Batyeva, E.S., Russ.
J. Gen. Chem., 2014, vol. 84, no. 8, p. 1648. DOI:
10.1134/S1070363214080386.
29. Kursheva, L.I., Yanberdina, N.V., Zvereva, E.E.,
Vandyukov, A.E., Reisenauer, M.R., Lujan, J.D.,
Lebrun, R.W., Edwards, L.D, Rogelj, S., Frolova, L.V.,
Batyeva, E.S., and Sinyashin, O.G., Heteroatom Chem.,
2014, vol. 25, p. 434. DOI: 10.1002/hc.21152.
10. Platova, E.V., Cand. Sci. (Chem.) Dissertation, Kazan,
2006.
11. Fridland, N.S., Ivanov, B.E., Krokhina, S.S., and
Platova, E.V., Zh. Org. Khim., 1994, vol. 30, no. 10,
p. 1462.
12. Redmore, D., J. Org. Chem., 1978, vol. 43, p. 992.
13. Zverev, V.V., Badeeva, E.K., and Krokhina, S.S., Russ.
Chem. Bull., 1992, vol. 41, no. 6, p. 1058.
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