A study on the selective phosphorylation and phosphinylation of hydroxyphenols

Article abstract of DOI:10.1002/hc.10006

By choice of appropriate reaction conditions, the phosphorylation of hydroquinone by diethyl chlorophosphate gave predominantly the monophosphate (2). A similar reaction of phloroglucinol led to the mixture of the possible products (6, 7, and 8). The mono

Full text of DOI:10.1002/hc.10006

Heteroatom Chemistry
Volume 13, Number 2, 2002
A Study on the Selective Phosphorylation
and Phosphinylation of Hydroxyphenols
Gyo¨rgy Marosi,1 Andrea Toldy,1 Gyula Parlagh,2 Zolta´n Nagy,3
Krisztina Luda´nyi,4 Pe´ter Anna,1 and Gyo¨rgy Keglevich1
1Department of Organic Chemical Technology, Budapest University of Technology
and Economics, 1521 Budapest, Hungary
2Department of Physical Chemistry, Budapest University of Technology and Economics,
1521 Budapest, Hungary
3Gedeon Richter Ltd., 1475 Budapest, Hungary
4Hungarian Academy of Sciences, Chemical Research Center, 1525 Budapest, Hungary
Received 24 April, 2001; revised 12 June 2001
retardants [1]. Among the polyols, whose “Achilles’
ABSTRACT: By choice of appropriate reaction condi-
heel” is their stability, the phosphorus containing
tions, the phosphorylation of hydroquinone by diethyl
derivatives such as aryl phosphates are also potential
chlorophosphate gave predominantly the monophos-
candidates as starting materials for flame retardants
phate (2). A similar reaction of phloroglucinol led to
[2]. It was a challenge for us to prepare hydroxyphe-
the mixture of the possible products (6, 7, and 8). The
nols with a phosphorus moiety in the aromatic ring
monophosphinylation of the above hydroxyphenols by
that can be used as additives or starting materials in
diphenylphosphinyl chloride could be accomplished
polycondensations to form flame retardants [3]. We
with a good selectivity to give product 4 or 9, the yields,
wished to make available some monophosphoryl-
ated and monophosphinylated polyhydroxyphenols.
C
however, being variable.
2002 Wiley Periodicals, Inc.
Heteroatom Chem 13:126–130, 2002; Published online
in Wiley Interscience (www.interscience.wiley.com). DOI
10.1002/hc.10006
RESULTS AND DISCUSSION
According to the literature, the acetylation of hy-
droquinone by acetyl chloride or acetic anhydride
gives a mixture of mono- and diacetylated prod-
ucts [4,5]. The use of acetic anhydride in acetic
acid afforded, however, 4-acetoxyphenol in 65% yield
[6]. Generally, monoacylation, including monophos-
phorylation, monophosphonylation, and monophos-
phinylation of dihydroxy compounds can be car-
ried out efficiently only if the two hydroxy groups
have different chemical natures, one of them being
spatially open and the other being shielded [7]. Phos-
phorus triamides were, however, found to be suit-
able reagents to achieve a predominant monoacyla-
tion of dihydric phenols [8]. The phosphorylation of
INTRODUCTION
Organophosphorus compounds used as monomers
or as additives form an important group of flame
Correspondence to: Gyo¨rgy Keglevich; e-mail: keglevich@oct.
bme.hu.
Contract grant sponsor: European Commission.
Contract grant number: EU-5 No. G5RD-CT-1999-00120.
Contract grant sponsor: Hungarian Scientific Research Fund.
Contract grant number: OTKA T 032941.
Contract grant sponsor: Ministry of Education.
Contract grant number: FKFP 363/1999.
2002 Wiley Periodicals, Inc.
c
126

Selective Phosphorylation and Phosphinylation of Hydroxyphenols 127
chromatography. The first fraction was practically
clean diphosphate 3, while the second one con-
tained monophosphate 2 in a purity of 86% and
in 31% yield. The products (2 and 3) were identi-
fied by 31P and 13C NMR spectra, as well as mass
spectroscopy including GC–MS for 2. Compound 2
was also characterized by HR–MS. The ␦P shift of
the 4-hydroxyphenyl diethyl phosphate was compa-
rable with that of the corresponding phenyl deriva-
tive ( 5.6 vs. 6.8) [11]. It is worth mentioning that
diphosphate 3 is a valuable starting material in the
synthesis of 1,4-disubstituted benzenes by a cross-
coupling approach [12].
The second model reaction was the phos-
phinylation of hydroquinone by diphenylphosphinyl
chloride. The acylation carried out in boiling ether,
in the presence of one equivalent of triethylamine
led to a mixture containing phosphinate 4 in 87%
and tetraphenyl pyrophosphinate (␦P (CDCl3) 32.1,
␦P lit [13] 32.6) in 13% yields according to 31P NMR
spectroscopy (Scheme 2). Product 4 was identified
by 31P and 1H NMR spectroscopy, as well as by mass
spectra. The selectivity is probably the consequence
of the poor solubility of the phosphinate (4) in ether.
The phosphorylation of phloroglucinol with di-
ethyl chlorophosphate at 35–82 C, in the presence
of triethylamine, afforded a mixture of the mono-,
di-, and triphosphates (6, 7, and 8, respectively), no
matter what was used as the solvent (Scheme 3, Table
2). No practical separation of the components could
be achieved. Monophosphate 6 could, however, be
separated from the experiment marked by entry 1
in a poor yield. The phosphates (6, 7, and 8) were
characterized by 31P NMR chemical shifts and mass
spectroscopical data obtained by MS or by GC–MS.
The reaction of phloroglucinol with diphenyl-
phosphinyl chloride in boiling ether, in the pres-
SCHEME 1
hydroxyphenols utilizing low-coordinate phospho-
rus fragments [9] did not seem to be a practical syn-
thesis in this particular case.
In the first place, we studied the phosphorylation
of hydroquinone by diethyl chlorophosphate under
different conditions (Scheme 1, Table 1). When the
phosphorylations in boiling ether or in acetonitrile
were carried out in the presence of one equivalent of
triethylamine, the proportion of the monophosphate
(2) and the diphosphate (3) was found to be com-
parable according to 31P NMR analysis of the crude
mixtures (ca. 41 vs. ca. 45%, respectively). Formation
of the tetraethyl pyrophosphate as a side product was
inevitable (Table 1, entries 1 and 2). The best results
were achieved by performing the phosphorylation in
boiling acetone; the selectivity of the monophospho-
rylation was found to be 0.79. Obviously, because of
the unremovable traces of the water, 28% of the py-
rophosphate was formed (entry 3). No phosphoryla-
tion took place in the absence of triethylamine. The
phase transfer catalytic method was proved not to
be suitable, as the liquid–liquid two-phase reaction
mixture containing aqueous sodium hydroxide led
predominantly to diphosphorylation (entry 4).
The crude product obtained by using acetone
as the solvent (entry 3) was refined by column
ence of
a tertiary amine resulted mainly in
TABLE 1 Phosphorylation of Hydroquinone by Diethyl Chlorophosphate Under Different Conditions
Product
Reaction
Compositiona (%)
nDECP
n1
Entry
Solvent
Base
TEA
TEA
TEA
Temp. ( C)
Time (h)
2
3
PPb
2/(2 + 3)
1c
2c
3c
4d
1.0
1.0
1.0
1.1
Ether
35
82
56
26
4.5
3
4.5
38
44
57
3
49
41
15
62
13
15
28
35
0.44
0.52
0.79
0.05
MeCN
Acetone
CH2Cl2
NaOH/H2O
Tebac
4.5
Abbreviations: diethyl chlorophosphate (DECP); pyrophosphate (PP); triethylbenzylammonium chloride (Tebac).
aDetermined on the basis of relative 31P NMR intensities.
b
(CDCl3) 12.9,
[10] 13.0.
P
P
cFor details see general procedure. The crude mixture obtained from the experiment marked by entry 3 was refined.
d1.32 ml DECP was added dropwise to the stirred mixture of 1.0 g of 1 and 0.62 g of Tebac in 60 ml of CH2Cl2 and 3.6 g NaOH in 10 ml of
water.

128 Marosi et al.
Phosphorylation of Hydroquinone
by Diethyl Chlorophosphate
To 0.5 g (4.55 mmol) of hydroquinone and 0.63 ml
(4.55 mmol) of triethylamine in 35 ml of the solvent
(Table 1) was added 0.68 ml (4.71 mmol) of diethyl
chlorophosphate, and the mixture was stirred at the
boiling point for the time shown in Table 1. The
solvent was evaporated and the residue taken up in a
mixture of 20 ml of chloroform and 2 ml of water. The
organic phase was dried (Na2SO4) and the solvent
evaporated. The crude mixture was analyzed by 31P
NMR spectroscopy (Table 1).
SCHEME 2
monophosphinylation. The acylation was, however,
rather slow and even after prolonged heating at the
boiling point, the yield of phosphinate 9 was only
17%. Some of the diphosphinylated product (10)
could also be detected by GC–MS; the ratio of 9 and
10 was 5:1 (Scheme 4). Compounds 9 and 10 were
characterized by 31P NMR and mass spectroscopical
data.
The crude mixture from the experiment marked
by entry 3 was subjected to column chromatography
(silica gel, 3% methanol in chloroform) to give 0.14
(11%) of product 2 in a purity of 86% and 0.45 g
(26%) of product 3 in a pure form.
2: 31P NMR (CDCl3)
␦
5.6; 13C NMR (CDCl3)
␦ 15.6 (J = 8.3, CH3CH2), 64.2 (J = 6.0, CH3CH2),
120.2 (C3), 120.7 (J = 4.1, C2), 142.7 (C4), 147.2
(J = 6.6, C1); GC–MS, m/z (rel. int.) 246 (M+, 47),
231 (M 15, 4), 218 (M 28, 23), 190 (218 28, 38),
137 ((EtO)2P(O), 2), 110 (M (EtO)2P(O) + H, 100),
109 (M (EtO)2P(O), 28); HRMS, M+found = 246.0602,
C10H15O5P requires 246.0657.
For the preparation of monophosphorylated
and monophosphinylated hydroquinone, the reac-
tion of p-benzoquinone with (EtO)2P(O)Na or with
Ph2P(O)Li was also described that was not too effi-
cient because of side reactions [14,15].
It can be concluded that while the monophos-
phinylation and the monophosphorylation of
hydroquinone can be achieved selectively, similar
reactions of phloroglucinol are rather complex: the
monophosphorylation is not selective, while the
monophosphinylation is fairly selective, but the
yield is poor.
3: 31P NMR (CDCl3) ␦ 5.94; 13C NMR (CDCl3)
␦ 15.8 (J = 6.6, CH3CH2), 64.5 (J = 6.1, CH3CH2),
120.9 (J = 4.6, C2), 147.3 (J = 6.6, C1); MS, m/z (rel.
int.) 382 (M+, 52), 367 (M 15, 2), 354 (M 28,
17), 326 (354 28, 12), 297 (326 29, 16), 246
(M (EtO)2P(O) + H, 45), 228 (245 17, 27), 200
(245 45, 63), 110 (246 (EtO)2P(O) + H, 68), 109
(246 (EtO)2P(O), 100).
In the next stage of our work, the phosphorylated
and phosphinylated hydroxyphenols will be incorpo-
rated into polymer composites in order to test their
flame retarding effect.
Phosphinylation of Hydroquinone
with Diphenylphosphinyl Chloride
EXPERIMENTAL
The 31P NMR spectra were taken on a Bruker DRX-
500 spectrometer operating at 202.4 MHz. Chemical
shifts are downfield relative to 85% H3PO4. GC–MS
was performed on a Fisons GC 8000/MD 800
apparatus.
The reaction was carried out as the phosphorylations
described previously using ether as the solvent and
0.87 ml (4.55 mmol) of diphenylphosphinyl chloride
as the acylating agent. The precipitated material was
filtered off and taken up in a mixture of 20 ml of
SCHEME 3

Selective Phosphorylation and Phosphinylation of Hydroxyphenols 129
TABLE 2 Phosphorylation of Phloroglucinol by Diethyl Chlorophosphate in Different Solvents in the Presence of One Equivalent
of TEA
Reaction
Temp. ( C)
Product Composition a (%)
Entry
Solvent
Time (h)
6
7
8
PP
6/(6 + 7 + 8)
1b
2b
3b
Ether
MeCN
Acetone
35
82
56
5
3
4.5
18
25
16
18
14
12
47
36
22
17
25
50
0.22
0.33
0.32
aDetermined on the basis of relative 31P NMR intensities.
bFor details see general procedure. The crude mixture obtained from the experiment marked by entry 2 was refined.
chloroform and 2 ml of water. The organic phase was
dried (Na2SO4) and the solvent evaporated to give
the phosphinate (4) in 90% yield, in a purity of ca.
90%. A small sample was recrystallized from chlo-
roform to afford pure 4. 31P NMR (CDCl3) ␦ 32.7;
1H NMR (CDCl3) ␦ 6.65–7.88 (m, 14H, ArH), 9.67
(s, 1H, OH); MS, m/z (rel. int.) 310 (M+, 51), 201
(Ph2P(O), 100), 77 (Ph, 22).
(M 28, 10), 355 (383 28, 11), 341 (370 29,
10), 262 (M (EtO)2P(O) + H, 21), 244 (261 17,
82), 233 (262 29, 25), 216 (261 45, 100), 188
(216 28, 23+), 136 ((EtO)2P(O) H, 53); HR–
FAB, (M + H)found = 399.0861, C14H25O9P2 requires
399.0974.
8: 31P NMR (CDCl3) ␦ 6.64; GC–MS, m/z (rel.
int.) 534 (M+, 37), 519 (M 15, 7), 506 (M 28,
9), 491 (519 28, 5), 478 (506 28, 12), 398
(M (EtO)2P(O) + H, 30), 380 (397 17, 100), 352
(397 45, 51), 324 (352 28, 52), 296 (324 28, 45),
216 (352 (EtO)2P(O) + H, 38), 136 ((EtO)2P(O) H,
13); HR–FAB, (M + H)+found = 535.1163, C18H34O12P3
requires 535.1263.
Phosphorylation of Phloroglucinol
by Diethyl Chlorophosphate
The reactions were carried out in the same man-
ner as for the phosphorylations of hydroquinone de-
scribed previously, 0.50 g (3.08 mmol) of phloroglu-
cinol, 0.43 ml (3.08 mmol) of triethylamine, 0.45 ml
(3.08 mmol) of diethyl chlorophosphate, and 25 ml
of acetone or acetonitrile, or 60 ml of ether being
used.
Phosphinylation of Phloroglucinol with
Diphenylphosphinyl Chloride
To 0.5 g (3.08 mmol) of phloroglucinol and 0.43
ml (3.08 mmol) of triethylamine in 60 ml of ether
was added 0.59 ml (3.08 mmol) of diphenylphos-
phinyl chloride, and the mixture was stirred at the
boiling point for 5 h. The precipitated material was
filtered off and the filtrate evaporated to give a
mixture containing 80% of the monophosphinate
(9), 16% of the diphosphinate (10), and 4% of the
pyrophosphinate.
The crude mixture from the experiment marked
by entry 1 was characterized after flash column chro-
matography (as above). A second chromatography
afforded monophosphate 6 in a pure form.
6: Yield: 5%; 31P NMR (CDCl3)
␦
6.57; 13C
NMR (CDCl3) ␦ 16.1 (J = 6.4, CH3CH2), 65.4 (J =
6.2, CH3CH2), 100.0 (J = 4.8, C2), 100.7 (C4), 151.8
(J = 7.0, C1), 158.3 (C3); MS, m/z (rel. int.) 262 (M+,
34), 247 (M 15, 10), 233 (M 29, 6), 219 (247 28,
29), 205 (233 28, 5), 136 ((EtO)2P(O) H, 100), 126
(M (EtO)2P(O) + H, 49), 108 (125 17, 13); HR–
FAB, (M + H)+found = 263.0614, C10H16O6P requires
263.0684.
9: 31P NMR (CDCl3) ␦ 32.0; GC–MS, m/z (rel.
int.) 326 (M+, 64), 201 (Ph2P(O), 100), 77 (Ph, 33).
10: 31P NMR (CDCl3) ␦ 32.7; GC–MS, m/z 526
(M+).
7: 31P NMR (CDCl3)
␦
6.45; GC–MS, m/z
(rel. int.) 398 (M+, 49), 383 (M 15, 11), 370
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