Synthesis and structure elucidation of new spiro compounds with polyfluoroalkyl and phosphonate ester groups

Article abstract of DOI:10.1080/00397910802537143

A series of spiro compounds with polyfluoroalkyl and phosphonate ester groups has been synthesized via several steps. The structures of these compounds were confirmed by 1H NMR,13C NMR, infrared (IR), and mass spectrometry (MS) as well. The possible reaction mechanism for the formation of these products was also proposed.

Full text of DOI:10.1080/00397910802537143

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Synthesis and Structure
Elucidation of New
Spiro Compounds with
Polyfluoroalkyl and
Phosphonate Ester Groups
Zhijian Shi a b , Yang Zhao a , Weiguo Cao a b , Shunli
Zhang a & Mei Liu a
a Department of Chemistry , Shanghai University ,
Shanghai, China
b Key Laboratary of Organofluorine Chemistry,
Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences , Shanghai, China
Published online: 19 Mar 2009.
To cite this article: Zhijian Shi , Yang Zhao , Weiguo Cao , Shunli Zhang & Mei
Liu (2009) Synthesis and Structure Elucidation of New Spiro Compounds with
Polyfluoroalkyl and Phosphonate Ester Groups, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:8,
1494-1503, DOI: 10.1080/00397910802537143
To link to this article: http://dx.doi.org/10.1080/00397910802537143
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Synthetic Communications1, 39: 1494–1503, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802537143
Synthesis and Structure Elucidation of New
Spiro Compounds with Polyfluoroalkyl
and Phosphonate Ester Groups
Zhijian Shi,1,2 Yang Zhao,1 Weiguo Cao,1,2 Shunli Zhang,1
and Mei Liu1
1Department of Chemistry, Shanghai University, Shanghai, China
2Key Laboratary of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, Shanghai, China
Abstract: A series of spiro compounds with polyfluoroalkyl and phosphonate
ester groups has been synthesized via several steps. The structures of these
compounds were confirmed by 1H NMR,13C NMR, infrared (IR), and mass
spectrometry (MS) as well. The possible reaction mechanism for the formation
of these products was also proposed.
Keywords: Phosphonate ester group, polyfluoroalkylated spiro compound,
structure elucidation
INTRODUCTION
Fluorine-containing organic compounds have played an important role
in synthetic organic chemistry and pharmaceutical chemistry because of
their biological activities. The ability of the fluorine atom to enhance
biological and therapeutical activities of certain organic compounds
has led to widespread interest in selective introduction of fluorine atoms
and fluoroalkyl groups into organic molecules.[1–3] The development of
synthetic methodologies in organofluorine chemistry has always been of
paramount importance. The cyclic compounds containing perflour-
Received September 10, 2008.
Address correspondence to Zhijian Shi and Weiguo Cao, Shanghai University,
Shanghai 200444, China. E-mail: shzhjian@shu.edu.cn; wgcao@staff.shu.edu.cn
1494

New Spiro Compounds
1495
oalkyl have drawn much more attention because of their unique physio-
logical and potential biological properties, which can be imparted by a
fluoroalkyl group. However, the preparation of perfluoroalkylated
organic compounds suffered from long synthetic procedures and the
difficulty of introducing the fluoroalkyl group.[4–14] In this article, we
report a simple synthesis of a series of spiro compounds, 5a–c and
6a–c, with per(poly)fuoroalkyl and phosphonate ester groups. The
possible mechanisms for the formation of these products were also
proposed.
RESULTS AND DISCUSSION
In the presence of KOH and PEG-400 in acetone at 57–60ꢀC, 1,5-
dioxa-spiro[5.5]undecane-2,4-dione (3)[15] reacted with 3-bromopro-
pene to give 3,3-diallyl-1,5-dioxa-spiro[5.5]undecane-2,4-dione (4).
Compound 4 reacted with perfluoroalkyl iodides (a–c) in a water–
acetonitrile biphasic solvent system, using Na2S2O4 and Na2CO3 as
initiators, to offer cyclic compounds 5a–c with high yields. The
reaction of compounds 5a–c with triethyl phosphite proceeded at
200ꢀC gave rise to the products 6a–c (Scheme 1, Table 1).
The structures of compounds 4, 5a–c, and 6a–c were confirmed by
1
means of infrared (IR), mass spectrometry (MS) (Table 2), H NMR,
and 13C NMR (Table 3).
Scheme 1. Synthesis of polyfluorinated spiro compounds.

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Z. Shi et al.
Table 1. Preparation of compounds 4, 5a–c, and 6a–c
Reaction
condition
Yield
(%)
Compound
Solvent
State
Mp
4
(CH3)2CO
60ꢀC 5 h Yellow oil
—
65
5a
5b
5c
6a
6b
6c
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
P(OCH2CH3)3 200ꢀC 2 h Yellow oil
P(OCH2CH3)3 200ꢀC 2 h Yellow oil
P(OCH2CH3)3 200ꢀC 2 h Yellow oil
0ꢀC 3 h White needle crystal 136.4–137.1 92
0ꢀC 3 h White needle crystal 125.5–126.8 91
0ꢀC 3 h White needle crystal 149.9–150.3 90
—
—
—
76
75
70
ꢁ
The reaction mechanism is shown in Scheme 2. The RF radical
derived from perfluoroalkyl iodides in the presence of sodium
dithionite and sodium carbonate attacked the carbon–carbon double
bond of compound 4, followed by cyclization, to form spiro compound
5. Then, the spiro compound 6 with polyfluoroalkyl and phosphonate
ester groups was obtained via the reaction of compound 5 with triethyl
phosphite.
EXPERIMENTAL
Melting and boiling points are uncorrected. IR spectra were recorded on
an Avatar 370 Fourier transform (FT) spectrophotometer; solid samples
were examined as KBr discs, and oil samples were examined as liquid
films. NMR spectra were determined with DRX 500-MHz spectrometer,
using solutions in CDCl3 with tetramethylsilane (TMS) as the internal
1
standard for H and 13C nuclei respectively. MS spectra were run on a
5979 MSD spectrometer.
General Procedure for the Preparation of 4
Potassium hydroxide (KOH) (5 mmol) and PEG-400 (0.2 mmol) were
added to
a
suspension of 1,5-dioxa-spiro[5.5]undecane-2,4-dione
(5 mmol) in acetone (25 ml), and the mixture was stirred at 50ꢀC for
5 min. 3-Bromopropene (10 mmol) was added and refluxed for 5 h.
The insoluble material was filtered off, and the solvent was evaporated
under reduced pressure. Then, 3,3-diallyl-1,5-dioxa-spiro[5.5]undecane-
2,4-dione (4) was collected by distillation (10 mmHg, 120–125ꢀC
fraction).

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1500

1501

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Z. Shi et al.
Scheme 2. Mechanism for the formation of spiro compounds.
Typical Procedure for the Preparation of 5a–c
Compound 4 (2 mmol) reacted with perfluoroalkyl iodides (a–c) (2 mmol)
in a water–acetonitrile biphasic solvent system (v=v ¼ 8:1) at 0ꢀC for 3 h
using sodium dithionite (Na2S2O4) and sodium carbonate (Na2CO3) as
initiators. After that, water (4 mL) was added to dissolve the inorganic
salts, and ethyl acetate (10 mLꢃ3) was added to extract organic com-
pounds. The organic layer was dried over anhydrous sodium sulfate.
The solvent was removed by evaporation under reduced pressure, and
the residue was recrystallized from ethyl acetate–petroleum (v=v ¼ 5:1)
to obtain pure product 5a–c.
Typical Procedure for the Preparation of 6a–c
Compounds 5a–c (2 mmol) reacted with triethyl phosphite (2 ml) at
200ꢀC and was kept boiling slightly for 2 h. Excess triethyl phosphite
was removed by evaporation under reduced pressure to give 6a–c.
ACKNOWLEDGMENTS
The authors are grateful to the National Natural Science Foundation of
China (20872088), Leading Academic Discipline Project of Shanghai

New Spiro Compounds
1503
Municipal Education Commission (Nos. J50102, 08ZZ44) for their
financial support. We also thank the Instrumental Analysis and Research
Center of Shanghai University for running all the NMR samples.
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