Practical synthesis of 6-chloro-dibenzo[c.e][1,2]oxaphosphorine

Article abstract of DOI:10.1080/00397911.2010.486504

The title P-heterocycle 3, a versatile intermediate in synthesis, was prepared by two independent methods. The first involves an environmentally friendly version of an old protocol starting from 2-phenylphenol (1) and phosphorus trichloride. Their interaction could be accomplished at 50C under solventless conditions. Cyclization of the intermediate (2) so obtained could be realized best under microwave conditions at 150C in the presence of ZnCl2. This method offers advantages over the traditional ones. According to another approach, the chloro-dibenzooxaphosphorine (3) was obtained by the novel reaction of 6H-dibenzo[c.e][1,2]oxaphosphorine-6-oxide (4) with phosphorus trichloride in boiling chloroform. Efficiency of the syntheses was demonstrated by converting the crude product 3 to a more stable phosphonic amide (6) that was stable enough to be isolated.

Full text of DOI:10.1080/00397911.2010.486504

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Practical Synthesis of 6-Chloro-
dibenzo[c.e][1,2]oxaphosphorine
Péter Ábrányi-Balogh a & György Keglevich a
a Department of Organic Chemistry and Technology , Budapest
University of Technology and Economics , Budapest , Hungary
Published online: 30 Mar 2011.
To cite this article: Péter Ábrányi-Balogh & György Keglevich (2011) Practical Synthesis of
6-Chloro-dibenzo[c.e][1,2]oxaphosphorine, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:10, 1421-1426, DOI:
10.1080/00397911.2010.486504
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Synthetic Communications1, 41: 1421–1426, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.486504
PRACTICAL SYNTHESIS OF
6-CHLORO-DIBENZO[c.e][1,2]OXAPHOSPHORINE
´
´
´
¨
Peter Abranyi-Balogh and Gyorgy Keglevich
Department of Organic Chemistry and Technology, Budapest University of
Technology and Economics, Budapest, Hungary
GRAPHICAL ABSTRACT
Abstract The title P-heterocycle 3, a versatile intermediate in synthesis, was prepared by
two independent methods. The first involves an environmentally friendly version of an old
protocol starting from 2-phenylphenol (1) and phosphorus trichloride. Their interaction
could be accomplished at 50 ꢀC under solventless conditions. Cyclization of the intermediate
(2) so obtained could be realized best under microwave conditions at 150 ꢀC in the presence
of ZnCl2. This method offers advantages over the traditional ones. According to another
approach, the chloro-dibenzooxaphosphorine (3) was obtained by the novel reaction of
6H-dibenzo[c.e][1,2]oxaphosphorine-6-oxide (4) with phosphorus trichloride in boiling
chloroform. Efficiency of the syntheses was demonstrated by converting the crude product
3 to a more stable phosphonic amide (6) that was stable enough to be isolated.
Keywords Cyclization; dibenzo[c.e][1,2]oxaphosphorine; microwave; substitution
INTRODUCTION
6-Chloro-dibenzo[c.e][1,2]oxaphosphorine is a versatile intermediate in organic
syntheses.[1–9] A number of substituted dibenzooxaphosphorine derivatives were
synthesized, including phosphinous and phosphonous derivatives.[1–6] In reaction
with chlorine, the corresponding phosphorane[7] formed the 6-H-dibenzooxapho-
sphorine 6-oxide on hydrolysis.[8]
In our laboratory, the chloro-dibenzooxaphosphorine was converted to aryl,[9]
amino,[10] and alkoxy[10,11] derivatives containing achiral[9–11] and chiral[10] represen-
tatives. The P(III) ligands so obtained were useful in the synthesis of the correspond-
ing bis(dibenzooxaphosphorino)platinum complexes[9,11,12] that may be catalysts in
Received November 10, 2009.
Address correspondence to Gyo¨rgy Keglevich, Department of Organic Chemistry and Technology,
Budapest University of Technology and Economics, H-1521 Budapest, Hungary. E-mail: gkeglevich@
mail.bme.hu
1421

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P. ABRANYI-BALOGH AND G. KEGLEVICH
1422
homogeneous catalytic processes.[13,14] Other dibenzooxaphosphorine-related and
ring Pt-complexes were also described.[15,16]
The chloro-dibenzooxaphosphorine under discussion may be prepared in two
steps. In the first step, o-phenylphenol is reacted with phosphorus trichloride at
140–150 ꢀC under solventless conditions, while in the second step, the phosphory-
lated species so obtained is subjected to an intramolecular ring closure at high tem-
perature (200–250 ꢀC) in the presence of ZnCl2.[4,17–19] According to the experiments,
the first step required at least 5 h of reaction time, while the second step, depending
on the temperature, was complete mostly after 2–4 h. The yields were almost quan-
titative.[4,18] The procedure is efficient but still not too attractive. It is not so simple
to react the components of a dense slurry at high temperature (200–250 ꢀC) in an
inert atmosphere for several hours. We wished to make use of the microwave
(MW) technique and to find the optimum set of parameters. In addition, we aimed
at other synthetic approaches.
RESULTS AND DISCUSSION
In the first part of our research, the solventless reaction of o-phenylphenol (1)
with phosphorus trichloride was studied. It was found that there is no need to per-
form phosphorylation at 140–150 ꢀC for >5 h as described,[4,17–19] as the reaction is
complete already after heating the components at 50 ꢀC for 3 h in a sealed tube under
nitrogen (Scheme 1). As regards the second step, the zinc-chloride-mediated closure
of species 2, the literature data (200–250 ꢀC, 2–4 h)[4,17–19] were again excessive, as we
found that in the presence of 40% of ZnCl2, the cyclization was complete already
after heating at 150 ꢀC for 2 h. In this case, the chloro-dibenzooxaphosphorine (3)
was obtained in a pure form. Using only 10% of the Lewis acid, the purity of the
product 3 was only 86%, as, in this case, minor unidentified by-products appeared
in the mixture (Scheme 1).
At this point, we tried to make use of MW irradiation. It was indeed useful, as
under MW conditions the ring closure was already complete after 0.5 h applying the
same (150 ꢀC) reaction temperature (Scheme 1). Again 40% of the catalyst had to be
used to get the chloro-dibenzooxaphosphorine (3) in a pure form. Isolated yields of
product 3 were practically quantitative in all cases.
We were successful in finding the optimum conditions for the 1 ! 2 ! 3
transformation. Contrary to the excessive reaction conditions suggested by the
literature,[4,17–19] the first and the second reaction steps can be performed at ca.
100 ꢀC lower than previously reported. Moreover, MW irradiation is helpful in car-
rying out the cyclization in a shorter reaction time.
Scheme 1. A two-step synthesis of chloro-dibenzooxaphosphorine.

6-CHLORO-DIBENZO[c.e][1,2]OXAPHOSPHORINE
1423
Scheme 2. Synthesis of chloro-dibenzooxaphosphorine by ‘‘chlorination.’’
Then we tried to utilize the commercially available 6H-dibenzo[c.e][1,2]
oxaphosphorine-6-oxide (4) in the preparation of chloro-dibenzooxaphosphorine
3. Our idea was to try to achieve the 4 ! 3 conversion by reaction with inorganic
chlorides. It was found that phosphorus trichloride is a suitable reagent. Using 1.5
equivalents of phosphorus trichloride in boiling chloroform for 3 h, the target mol-
ecule (3) was obtained practically quantitatively and in a purity of 97% after evap-
oration of the volatile components (Scheme 2). The H-dibenzooxaphosphorine
oxide (4) is also present in its tautomeric form, that is, a phosphonous acid (40). This
species (40) may react with phosphorus trichloride to afford the chloro-
!
dibenzooxaphosphorine (3). Evidently a >PðOÞH >POH tautomeric equilibrium
is responsible for the chlorination. It was interesting to learn that other halides, such
as thionyl chloride or triphosgene, were inefficient or caused side reactions. This
novel type of synthesis of a >PCl derivative from the corresponding >P(O)H species
may be of more general value. A single example has been described for the conver-
sion of a H-phosphinate to the corresponding phosphonous ester chloride by the
action of a special halogen transfer agent, Ph3PCl2.[20]
Efficiency of these syntheses was tested by converting the crude chloro-
dibenzooxaphosphorine (3), which is a highly hydrolizable molecule, to the
corresponding phosphonamide (6). In the first step, the phosphonous chloride 3 is
transformed to the amide (5), followed by oxidation to the stable tetracoordinated
form (6) (Scheme 3). The yields of phosphonamide 6 obtained after flash column
chromatography were the indicators of the efficiency of the syntheses described by
us. According to this, in all the three cases the yield of 6 was in the range of 86–91%.
In conclusion, two independent synthetic methods have been elaborated for
the preparation of 6-chloro-dibenzo[c.e][1,2]oxaphosphorine that are attractive as
they are easy to accomplish. One of the methods uses the phosphorylation of
2-phenylphenol and the ring closure of the intermediate obtained under relatively
mild and ‘‘green’’ conditions. The other protocol involves chlorination of the phos-
phonous tautomer of the corresponding H-phosphinate by phosphorus trichloride.
Scheme 3. Conversion of the chloro-dibenzooxaphosphorine to the corresponding amide-ester 6.

´ ´
P. ABRANYI-BALOGH AND G. KEGLEVICH
1424
EXPERIMENTAL
The 31P NMR spectra were obtained on a Bruker DRX-500 spectrometer
operating at 202.4 MHz. Chemical shifts are downfield relative to 85% H3PO4.
The MW-assisted cyclizations were carried out in a CEM Discover microwave
reactor using 20–50 W of irradiation.
6-Chloro-dibenzo[c.e][1,2]oxaphosphorine (3)
Method A. 2-Phenylphenol (1) (0.20 g, 1.18 mmol) and 0.20 ml (0.32 g,
2.35 mmol) of phosphorus trichloride were charged into a vial, without solvent.
The mixture was stirred at 50 ꢀC for 3 h to yield the phosphorylated phenylphenol
2. Zinc chloride (0.016 g, 0.12 mmol) was added to the mixture, and the vial was
placed in the microwave reactor and irradiated at 150 ꢀC for 0.5 h. The crude product
(3) so obtained was analyzed. 31P NMR (CDCl3) d 133.2 (dP 133.3). Purity 90%;
[4]
yield ꢁ100%. When the experiment was repeated using 0.08 g (0.51 mmol) of zinc
chloride in the second step, the purity of the product (3) so obtained quantitatively
was 100%.
Method B. The procedure described under Method A was repeated, but the
second step was also performed thermally at 150 ꢀC for 2 h. When 0.016 g (0.12 mmol)
of zinc chloride was used, the purity of product 3 was 86%. When 0.08 g (0.51 mmol)
of zinc chloride was added, the purity of 3 was 100%. The yield was in both cases
practically quantitative.
Method C. 6H-Dibenzo[c.e][1,2]oxaphosphorine 6-oxide (4) (0.20 g, 0.93mmol)
was dissolved in 20 ml of dry chloroform, and 0.12 ml (0.19 g, 1.39 mmol) of phosphorus
trichloride was added in a nitrogen atmosphere. The mixture was stirred at the boiling
point for 3 h. The solvent was removed under vacuum to give 0.23 g (100%) of crude
product 3 as a yellowish oil. 31P NMR (CDCl3) d 133.3 (dP[4] 133.3); purity 97%.
6-Diethylamino-dibenzo[c.e][5,6]oxaphosphorine 6-Oxide (6)
The crude 6-chloro-dibenzo[c.e][1,2]oxaphosphorine (3) (0.21 g, ꢁ0.9 mmol)
obtained by Method A (using 40% of ZnCl2) was dissolved in 10 ml of toluene,
and 0.20 ml (1.85 mmol) of diethylamine was added at 26 ꢀC with intensive stirring.
The mixture was stirred at 26 ꢀC for 3 h. The solvent was removed under vacuum to
give 0.255 g (94%) of crude product 5 as a yellowish oil (31P NMR (CDCl3) d 91.6;
purity ꢁ90%).
The crude 5 (ꢁ0.85 mmol) obtained in the previous experiment was dissolved in
15 ml of dry chloroform, and 0.34 ml of 30% H2O2 (0.38 g, 1.10 mmol) was added at
0 ꢀC with intensive stirring. Then the mixture was allowed to warm up to 26 ꢀC and
stirred for 1 h. The mixture was extracted with 2 ꢂ 5 ml water, and the organic layer
was dried (Na2SO4). The solvent was removed under vacuum, and the crude product
so obtained was purified by column chromatography (silica gel, chloroform–
methanol 97:3) to furnish 0.23 g (89% [based on 3]) of product 6 in a pure form.
Results of the similar reaction sequences starting from 3 obtained by methods
B and C are also shown in Table 1.

6-CHLORO-DIBENZO[c.e][1,2]OXAPHOSPHORINE
1425
Table 1. Yields of phosphonic amide 6 as an indicator of the efficiency of methods A–C
dP (CDCl3)
for 3
Isolated yield of 6 based
on crude 3 (based on 5)
dP (CDCl3) for
6 (dP 17.0)
[10]
The source of crude 3
Method A (40% ZnCl2)
Method B (40% ZnCl2)
Method C
133.2
133.3
133.3
89% (94%)
91% (94%)
86% (89%)
16.5
16.5
16.6
ACKNOWLEDGMENTS
This above project was supported by the Hungarian Scientific and Research
Fund (OTKA K067679 and K83118). The authors are grateful to Dr. Harry R.
Hudson (London Metropolitan University) for his advice.
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