Effect of isopropyl group on phosphorylation of phenols with phosphorous amides

Article abstract of DOI:10.1023/A:1020807208325

Reaction of resorcinol with phosphorous triamides containing various aliphatic radicals was studied. The preferential cleavage from phosphorus of the diisopropylamino group compared with the less bulky dimethylamino group was observed for the first time. It was shown that resorcinol is easily phosphorylated under mild conditions independent of the nature of substituent on nitrogen, but sterically hindered bulky radicals on nitrogen slow down phenolysis not only of the first, but also of the second amido group.

Full text of DOI:10.1023/A:1020807208325

Russian Journal of General Chemistry, Vol. 72, No. 8, 2002, pp. 1183 1185. Translated from Zhurnal Obshchei Khimii, Vol. 72, No. 8, 2002,
pp. 1263 1266.
Original Russian Text Copyright
2002 by Nifant’ev, Suvorkin, Rasadkina, Selyutina, Shishin.
Effect of Isopropyl Group on Phosphorylation of Phenols
with Phosphorous Amides
E. E. Nifant’ev, S. V. Suvorkin, E. N. Rasadkina, O. V. Selyutina, and A. V. Shishin
Moscow State Pedagogical University, Moscow, Russia
Received November 16, 2000
Abstract Reaction of resorcinol with phosphorous triamides containing various aliphatic radicals was
studied. The preferential cleavage from phosphorus of the diisopropylamino group compared with the less
bulky dimethylamino group was observed for the first time. It was shown that resorcinol is easily phosphory-
lated under mild conditions independent of the nature of substituent on nitrogen, but sterically hindered bulky
radicals on nitrogen slow down phenolysis not only of the first, but also of the second amido group.
Phosporylation of alcohols and phenols with di-
alkylamides of trivalent phosphorus acids has been
widely studied [1]. Much emphasis in these works has
been put on the effect of the nature of substituents on
phosphorus on the reaction progress. At the same time,
the effect of the size and other properties of alkyl
substituents on nitrogen on the dynamics of such re-
actions has not been considered.
proposed that introduction of more bulky radicals, such
as isopropyl or piperidyl, to the nitrogen atom of the
amido group would diminish the amount of by-products
and improve crystallization of the target compounds.
This work was begun with investigation of the re-
action of resorcinol (I) with the equivalent amount of
unsymmetrical phosphorous triamide II containing two
dimethylamino and one diisopropylamino group. We
proposed that the reactions would involve initial sub-
stitution of the less bulky and more reactive dimethyl-
In the previous works [2, 3], we used hexamethyl-
and hexaethylphosphorous triamides as phosphorylat-
ing agents for preparing phosphorus-containing macro- amido groups. But it occured that at room temperature
heterocycles on the basis of aromatic diols. As a rule,
the obtained compounds were viscous oils, which
complicated their isolation and investigation. We
phosphorylation of resorcinol begins with substitution
of the heavier diisopropylamino group to form pro-
duct III which was previously obtained in [4].
O
O
O
O
+
(Me N) PN(i-Pr)
Me N P
P NMe2
2
2
2
2
HO
OH
I
II
III
This conclusion was made on the basis of spectral
data. The 31P NMR spectrum of the obtained com-
Since the use of unsymmetrical triamide II did not
lead to the expected results, we tried as phosphorylat-
ing agents symmetrical phosphorous amides, such as
phosphorous tris(diisopropylamide) and tripiperidide
pound contained one singlet with
139.9 ppm,
P
characteristic of cyclic phosphoramidites containing a
1
dimethylamino group. The H NMR spectrum con-
(IV, V).
tained, together with aromatic proton signals, a doublet
at 2.73 ppm assignable to the dimethylamino group.
It was shown that phosphorous amides IV, V
readily and successfully react with resorcinol. The
reactions are complete at room temperature within one
Deceased.
1
070-3632/02/7208-1183$27.00 2002 MAIK Nauka/Interperiodica

1184
NIFANT’EV et al.
1
day and give cyclic phosphoramidites VI, VII in high
yields. Hence, the new phosphorous triamides proved
to be effective phosphorylating agents. The resulting
phosphorus-containing macrocycles VI, VII are oils.
142.3 and 135.8 ppm, respectively. The H NMR
spectra of these compounds agree with the proposed
structures. For a more complete identification, cyclic
phosphoramidites VI, VII were converted to the cor-
responding phosphoramidothioates VIII, IX.
Their 31P NMR spectra contain single singlets at
P
P(NR2)3
O
O
O
O
S
O
O
O
O
S
S
I
R2N P
P NR2
P
P
IV, V
R2N
NR2
VI, VII
VIII, IX
(V, VII, IX).
R = i-Pr (IV, VI, VIII), N
With the purpose of a more detailed investiga-
tion of the effect of the size of substituent in the
phosphoramidite moiety on the rate of phenolysis of
phosphoramidites we performed comparative ana-
lysis of the rates of reactions of phosphorous tris-
means of 31P NMR spectroscopy. The reactions
were carried out in dioxane, since, as we showed
previously [2, 5], phenolysis of phosphorous triamides
in dioxane proceeds rather slowly. For this reason,
we could more effectively trace the reaction pro-
gress.
(dimethylamide) and tripiperidide with resorcinol by
a, b
O
O
O
O
2
P(NR2)
2
HO
3
R2N P
P NR2
O(PNR2)2
V, X
XI, XII
R = Me (X, XI, XIII), N
XIII, XIV
(V, XII, XIV).
Here a stands for the reaction with triamide X and b
stands for the reaction with triamide V. P, ppm:
tion a reaches 78%, while in reaction b, only 30%.
After 3 days, reaction a is practically complete, while
the amount of phosphoramidite XIV in reaction b re-
aches 55% only. Hence we showed that sterically
hindered bulky radicals on nitrogen slow down phe-
nolysis not only of the first, but also the second amido
group, but in such solvents as diethyl ether and aceto-
nitrile this difference is insignificant.
1
16.5 (V), 122.2 (X), 135.0 (XI), 126.7 (XII), 139.2
(XIII), and 135.7 (XIV).
It was shown that in the first minutes of the reac-
tion the rate of substitution of the first amido group is
slightly higher in reaction b. Then the amount of
monophosphorylated resorcinol in reaction a increases
2
1
.5 times, and in reaction b only 1.3 times. After
day, the amount of cyclic phosphoroamidite in reac-
To conclude, cyclophosphorylation of resorcinol
proceeds easily and successfully under mild condi-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 8 2002

EFFECT OF ISOPROPYL GROUP ON PHOSPHORYLATION OF PHENOLS
1185
tions independent of the nature of substituent on
nitrogen. This opens up a synthetic approach to
macroheterocyclic compounds with various phos-
phamide groups.
of resorcinol (I) in 9 ml of diethyl ether, 1.8 mmol of
hexaalkylphosphorous triamide IV, V was added with
vigorous stirring at room temperature. The reaction
mixture was kept at room temperature for a day, and
the solvent was removed in a vacuum. Compound
EXPERIMENTAL
VI: R 0.9 (A), 0.83 (B), and 0.74 (C);
142.3 ppm.
f
P
Compound V: R 0.62 (A), 0.7 (B), and 0.95 (C);
f
P
1
The H NMR spectra were recorded in CDCl on a
135.83 ppm. The reaction product was dissolved in 3
ml of benzene, and 2.97 mmol of sulfur was added.
The reaction mixture was kept at room temperature
for a day. The solvent was removed in a vacuum, and
compounds VIII, IX were isolated by column chro-
matography, eluent 10:1 benzene dioxane. After
removal of the solvents in a vacuum, an oilish residue
was kept in a vacuum for 3 h [30 C (1 mm)].
3
Bruker WH-250 (250 MHz) spectrometer against
internal TMS. The P NMR spectra were obtained
on a Bruker-80 SY (32.4 MHz) spectrometer against
5% phosphoric acid. Column chromatography was
carried out on Silica gel L 100/250, and TLC, on
Silufol plates, eluents 3:1 benzene dioxane 3:1 (A),
4:1 benzene hexane (B), and 3:1 chloroform
methanol (C), development by calcination and by
treatment with 1% aqueous AgNO . Phosphorous tri-
piperidide (V) was prepared according to [6].
3
1
8
3
5
5
3
,7-Diisopropylamino-2,4,6,8-tetraoxa-3 ,7 -
3
diphospha-1,5(1,3)-dibenzenacyclooctaphane 3,7-
disulfide (VIII). Yield 65%, R 0.42 (A), 0.3 (B),
f
1
N,N-Diisopropyl-N ,N ,N ,N -tetramethylphos-
phorous triamide (II). To a solution of 13.75 g of
phosphorus trichloride in 500 ml of hexane, a mixture
of 10.1 g of diisopropylamine and 10.1 g of triethyl-
amine was added with stirring and cooling to 0 C.
The reaction progress was controlled by P NMR
spectroscopy. After the reaction was complete, dry
dimethylamine was passed through the resulting solu-
tion for 1 h, and then the reaction mixture was left to
stand at room temperature for a day. The precipitate
that formed was filtered off, and the solvent was re-
0.92 (C). H NMR spectrum, , ppm: 1.33 br.s (24H,
CH ), 3.62 m (4H, CH), 6.46 br.s, 6.78 m, 7.18 m
3
(8H, CH arom.).
60.0 ppm, s. Calculated, %: C
P
53.07, H 6.63, P 11.42. C H N O P S . Found, %:
2
4
36
2
4 2 2
C 53.13; H 6.69; P 11.25.
3
1
5
5
3,7-Dipiperidino-2,4,6,8-tetraoxa-3 ,7 -di-
phospha-1,5(1,3)-dibenzenacyclooctaphane 3,7-di-
sulfide (IX). Yield 67%, R 0.24 (A), 0.03 (B), 0.77
f
1
(C). H NMR spectrum, , ppm: 1.54 s (12H, CH
2
CH CH ), 3.39 s (8H, NCH ), 6.38, 6.66, 6.79,
2
2
2
7.13 br.s (8H, CH arom.).
63.34 ppm. Calculated,
P
moved under reduced pressure. The residue was dis- %: C 51.70; H 5.48; P 12.14. C H N O P S .
2
2
28
2
4 2 2
tilled in a vacuum [64 65 C (3 mm)]. Yield 18.83 g
Found, %: C 51.46; H 5.40; P 12.04.
0
1
(
86%), n2 1.4724. H NMR spectrum, , ppm: 0.74 d
D
3
ACKNOWLEDGMENTS
(
12H, CH i-Pr, J 5.9 Hz), 2.41 d (12H, N CH3,
JHP 12.79 Hz), 3.15 m (2H, CH).
Found, %: C 54.71; H 11.85, P 14.18. C H N P.
Calculated, %: C 54.79, H 11.87, P 14.15.
3
HH
3
106.4 ppm.
P
The work was financially supported by the Uni-
versitety Rossii fundamental’nye issledovaniya
Program (project no. 2211)
1
0
26
3
Hexaisopropylphosphorous triamide (IV). To a
solution of 0.2 g of phosphorus trichloride in 50 ml of
benzene, a mixture of 0.45 g of diisopropylamine and
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0
.44 g of triethylamine in 40 ml of benzene was ad-
ded with stirring and cooling to 0 C. The reaction
mixture was kept at room temperature for a day, the
precipitate that formed was filtered off, and the sol-
vent was removed at reduced pressure. Phosphorous
triamide IV was isolated pure by vacuum distillation
(
1
150 C, 1 10 4 mm). Yield 0.2 g (42%), mp 140
44 C, R 0.36 (A), 0.30 (B), 0.97 (C). H NMR spec-
1
f
3
trum, , ppm: 1.24 d, 1.27 d (18H, CH , J 6.12
Hz), 3.68 m (3H, CH, J 6.37 Hz). 130.1 ppm, s.
3
HH
3
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Subbotina, L.S., in Fosfororganicheskie soedineniya i
polimery (Organophosphorus Compounds and Poly-
mers), Cheboksary, 1976, issue 1, p. 33.
HH
P
Calculated, %: C 65.21; H 12.77; P 9.34. C H N P.
1
8
42
3
Found, %: C 65.12; H 12.74; P 9.33.
Cyclic bis(O,O-m-phenylene dialkylphosphor-
amidothioates) VIII, IX. To a solution of 1 mmol
6. Thorstenson, T., Acta Chem. Scand., Sect. A, 1976,
vol. 30, p. 781.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 72 No. 8 2002