Electrospray ionization mass spectrometry: A powerful tool to investigate the oligomerization mechanism of tetrahydrofuran by phosphoryl chloride

Full text of DOI:10.1002/jms.822

JOURNAL OF MASS SPECTROMETRY
J. Mass Spectrom. 2005; 40: 546–548
Published online 15 February 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jms.822
JMS Letters
Received 5 November 2004; Accepted 22 December 2004
It is remarkable that halogen-containing compounds are very
useful intermediates in organic synthesis.7 For example, they can
react with nucleophiles such as amines and alkoxides to give
corresponding substituted products.
Dear Sir,
In this paper, positive-ion mode electrospray ionization mass
spectrometry (ESI-MS) was applied to trace the process of polymer-
ization. Mass spectra were acquired using a Bruker ESQUIRE-3000-
plus-LC ion trap spectrometer equipped with a gas nebulizer probe,
capable of analyzing ions up to m/z 6000. Nitrogen was used as
drying gas at a flow-rate of 41 minꢀ1. The nebulizer pressure was
7 psi. The capillary was typically held at 4 kV. The samples dissolved
in methanol were ionized by ESI and continuously infused into the
ESI chamber at a flow-rate of 4 µl minꢀ1 with a Cole-Parmer Model
74 900 syringe pump. The MHC ions were analyzed by multi-stage
tandem mass spectrometry through the collision with helium.
We found that phosphoryl chloride is able to promote the ring
opening and polymerization of THF followed by a sequence of
successive nucleophilic reactions simply by non-catalytic refluxing.
In order to reveal the reaction mechanism, at various time intervals,
0.5 ml of the solution was quenched with water and tested
immediately by positive-ion mode ESI-MS. It was found that when
the reaction proceeded for 4 h, the peaks of a series of products
at m/z 261, 333, 405 and 477 with a spacing of 72 Da, other than
that of phosphoric acid and related compounds, peaks at m/z 99
(protonated H3PO4) and 197 (proton-bound dimer of H3PO4), are
formed, as shown in Fig. 1, MS(1). As the reaction time was increased
to 6–7 h, in addition to the series mentioned above, two new series
of compounds formed, namely one series at m/z 251, 323, 395 and
467 with a spacing of 72 Da, as shown in Fig. 1, MS(2), and the other
at m/z 271, 343, 415 and 487, as shown in Fig. 1, MS(3).
Electrospray ionization mass spectrometry: a powerful tool to
investigate the oligomerization mechanism of tetrahydrofuran by
phosphoryl chloride
The ring-opening polymerization of tetrahydrofuran (THF) initiated
by trialkyloxonium salts was first described by Meerwein1 in 1939. In
subsequent studies,2 several initiators were also found to be effective
in THF polymerization to high molecular mass polymers.3–7
Reaction of THF with a variety of inorganic acid chlorides, such as
POCl3, SOCl2 and SiCl4, together with catalysts, such as Zn, ZnCl2,
H2SO4, TiCl4, BCl3 and MoCl5, were also examined.8–11 These
reactions produce open-chain oligomers of THF (1; R, R0 D OH, Cl,
Br; n ½ 0) in which the degree of polymerization depended greatly
on the reaction conditions. However, the detailed mechanism of the
reaction of THF with POCl3 has not been investigated.
R
R′
n
O
1
ŁCorrespondence to: Yu-Fen Zhao, Department of Chemistry and
Key Laboratory for Chemical Biology of Fujian Province, Xiamen
University, Xiamen 361005, China. E-mail: yfzhao@xmu.edu.cn
Contract/grant sponsor: Chinese National Science Foundation;
Contract/grant number: 20175026.
It should be noted that all the spacings of these three homologous
series of compounds are 72 Da, which corresponds to one molecule
of THF. Hence the production of all three series of compounds with
different structures are due to the polymerization of THF.
The relationship of these three types of compounds deduced
through their relative appearance rates is shown in Scheme 1. First,
the nucleophilic attack on POCl3 by the oxygen atom on THF gives
Contract/grant sponsor: Fujian Key Foundation of Science and
Technology; Contract/grant number: 2001F008.
Intens
x105
+MS
2 hours
196.8
2
1
99.2
260.8
260.9
294.6
72
127.1
171.0
332.9
0
x105
+MS
4 hours
72
1.0
0.5
99.2
MS (1)
196.8
171.0
72
332.9
127.1
404.9
476.9
0.0
x104
+MS
6 hours
72
72
6
4
2
72
332.9
MS (2)
250.9
260.9
322.9
395.0
405.0
467.0
477.0
99.2
549.0
163.0
196.8
0
x104
+MS
7 hours
72
72
72
6
4
2
0
342.8
MS (3)
414.8
405.0
486.8
477.0
271.0
102.3
163.0
549.0
127.1
196.9
100
200
300
400
500
m/z
Figure 1. Positive-ion mode ESI mass spectra for tracing the reaction of phosphoryl chloride refluxing in THF at different times.
Copyright  2005 John Wiley & Sons, Ltd.

JMS letters 547
Scheme 1. A possible reaction mechanism of POCl3-promoted ring opening and oligomerization of THF.
have been applied to investigate the polymerization process.
an active intermediate 2 (oxonium), capable of being ring opened by
the second THF molecule. Then the repetition of this step builds the
active intermediate oligomer 2oligomer. Through path A, a chloride
anion can terminate the polymerization to yield the first type of
compounds 3P-Cl, which are identified by MS through hydrolysis,
as shown in Fig. 1, MS (1), with the general molecular mass
189 C n72 Da. The series of compounds 3P-Cl can be converted into
the dichloro ether 5 with the general molecular mass 199 C n72 Da,
as shown in Fig. 1, MS (3), by a chloride anion replacement of the
phosphorodichloridate anion (R). Through path B, the 2oligomer
species can be trapped by the phosphorodichloridate anion (R)
to produce the 4PP-Cl, which are also identified by MS through
hydrolysis, as shown in Fig. 1, MS (2), with the general molecular
mass 179 C n72 Da. 4PP-Cl can also be converted into the dichloro
ether 5 by two chloride anion double nucleophilic substitutions.
Of course, the mechanism proposed in Scheme 1 is only one
of the possible mechanisms. A different mechanism can be also
suggested. For example, 5 can be obtained through the double
chlorine anion substitutions on the 2oligomer, 4PP-Cl can be
converted into 3P-Cl by a chlorine anion substitution on one of
the phosphorate groups on 4PP-Cl, etc.
In addition, the degree of polymerization depends on the molar
ratio of THF to POCl3. When 2 mol of THF were refluxed with
1 mol of POCl3 for 9 h, after work-up the pure bis(4-chlorobutyl)
ether was isolated by distillation under reduced pressure in 55%
yield (Scheme 2). Therefore, this method provides a simple way to
synthesize a symmetrical ether with two chlorine atoms at both ends.
In conclusion, ESI-MS is a powerful tool to trace the successive
ring opening and polymerization of THF by POCl3. It is found
that, as the reaction proceeds, three types of homologous oligo-
THF incorporated compounds are produced. A possible mechanism
to correlate these types of compounds is illustrated. In the
literature,12–17 other means, such as NMR and chromatography,
However, these methods have disadvantages when they are
applied to study complicated polymerization reactions such as
those considered here. Although gas chromatography (GC) and
liquid chromatography (LC) could separate all components, the
relationships between them are still a puzzle. Of course, LC/MS
and GC/MS are very useful techniques, but it takes time to
optimize the various conditions. In contrast, ESI-MS provides a
quick, economical and precise method to identify the polymerization
intermediates and products, which cannot be matched by other
methods. For example, 1H and 13C NMR spectroscopy can provide
specific structure determinations for pure compounds in general.
However, for complicated mixtures, NMR shows many peaks that
cannot be easily sorted out for different types of structure. Using
the methodology reported in this paper, ESI-MS combined with
other modern techniques can be applied to study complicated
polymerization mechanisms.
The authors are grateful for financial support from the Chinese
National Science Foundation (No. 20175026) and Fujian Key
Foundation of Science and Technology (No. 2001F008).
Yours,
GUI-JI ZHOU,1 PENG-XIANG XU,1 YONG YE2 and YU-FEN
ZHAO1,2Ł
1
Department of Chemistry and Key Laboratory for Chemical Biology of Fujian
Province, Xiamen University, Xiamen 361005, China
2
Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology,
Ministry of Education, Department of Chemistry School of Life Science and
Engineering, Tsinghua University, Beijing 100084, China
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Scheme 2
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548
JMS letters
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J. Mass Spectrom. 2005; 40: 546–548