Microwave irradiation in organophosphorus chemistry. III. Moderate scale synthesis of reagents for olefin formation

Article abstract of DOI:10.1081/SCC-100106048

Representative phosphonates and phosphonium salts have been prepared on a moderate scale (25-50 g) using a domestic microwave oven. The reactions, conducted in sealed hydrogenation vessels, showed remarkable rate acceleration and excellent yields (>95%) employing this methodology.

Full text of DOI:10.1081/SCC-100106048

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MICROWAVE IRRADIATION IN ORGANOPHOSPHORUS
CHEMISTRY. III. MODERATE SCALE SYNTHESIS OF
REAGENTS FOR OLEFIN FORMATION
a
James J. Kiddle
a
Department of Chemistry, University of North Carolina at Wilmington, 601 South
College Road, Wilmington, NC, 28403, U.S.A.
Version of record first published: 20 Aug 2006
To cite this article: James J. Kiddle (2001): MICROWAVE IRRADIATION IN ORGANOPHOSPHORUS CHEMISTRY. III. MODERATE
SCALE SYNTHESIS OF REAGENTS FOR OLEFIN FORMATION, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:21, 3377-3382
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SYNTHETIC COMMUNICATIONS, 31(21), 3377–3382 (2001)
MICROWAVE IRRADIATION
IN ORGANOPHOSPHORUS
CHEMISTRY. III. MODERATE
SCALE SYNTHESIS OF REAGENTS
FOR OLEFIN FORMATION
James J. Kiddle*
Department of Chemistry, University of North
Carolina at Wilmington, 601 South College Road,
Wilmington, NC 28403, USA
ABSTRACT
Representative phosphonates and phosphonium salts have
been prepared on a moderate scale (25–50 g) using a domestic
microwave oven. The reactions, conducted in sealed hydroge-
nation vessels, showed remarkable rate acceleration and
excellent yields (>95%) employing this methodology.
1
Since the appearance of the first papers on the application of micro-
wave irradiation in organic synthesis, the field has seen a steady growth to
the point where a variety of transformations are now possible with micro-
2
wave heating. Carrying out reactions using microwave heating, as opposed
*
E-mail: kiddlej@uncwil.edu
3
377
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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KIDDLE
to conventional heating, has the major advantage of shorter reaction times
because of the rapid heating. Consequently, reactions exhibit cleaner
products and more facile work up procedures.
Recently, this laboratory has focused on the development of method-
ologies for the synthesis of organophosphorus compounds using microwave
heating. The utility of microwave heating in organophosphorus chemistry
3
has been demonstrated by the facile and rapid syntheses of phosphonates,
4
5
phosphonium salts, and amino phosphonic acids. However, in each of
these reactions the scale was limited (1–2 g) by the necessity of conducting
6
the reaction in a threaded Teflon capped pressure tube. Although larger
pressure tubes are available, the length of these tubes does not allow for
the vertical placement of the reaction in the microwave oven, and thus
constitutes a serious limitation for the scale-up of reactions which use press-
ure tubes. Therefore, development of a generally applicable method
for moderate scale microwave synthesis utilizing sealed tubes seemed
useful. In addition, since many of the phosphonates and phosphonium
salts previously synthesized are useful organic reagents, the development
of a method for the moderate scale production of these compounds
seemed warranted.
In order to achieve this goal it was necessary to identify a vessel which
could withstand pressure and temperature changes, fit vertically in a domes-
tic microwave oven, and be easily sealed preferably with an inert threaded
cap. These criteria were easily met by the ready availability of threaded
hydrogenation vessels for hydrogenation reactors, and a Teflon cap sealed
with an o-ring. The configuration of the hydrogenation vessel is identical to
the pressure tubes used, but offer a variety of sizes (volumes) which will
easily fit vertically in a domestic microwave oven.
To test the utility of the hydrogenation vessels for moderate scale
microwave synthesis, six representative organophosphorus reagents for
olefin formation were selected as targets to demonstrate this methodology.
Three phosphonium salts (Table 1) and three phosphonates (Table 2) were
synthesized on a moderate scale (25–50 g) using the hydrogenation vessel.
The desired phosphonium salts (3a–c) were synthesized by microwave-
heated quaternization of triphenylphosphine (1) with an organic halide
(
2a–c). Interestingly, the increased concentration in these moderate scale
syntheses had a dramatic effect on the reactions showing both shorter
reaction times and improved yields, compared to those previously obtained
4
on a smaller scale.
Although the change in concentration is the likely cause of these
effects, additional factors cannot be excluded (i.e., pressure), and more pre-
cise investigations are necessary to determine the specific reason for the
improved yields and shorter reaction times.

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ORGANOPHOSPHORUS CHEMISTRY. III
3379
As seen with the phosphonium salts, the conversion of the alkyl
halides (2a–c) to phosphonates (5a–c) using triethyl phosphite (4) proceeded
in a straight-forward fashion. Again these rearrangements occurred
with better yields, and for shorter times then those previously reported for
3
smaller scale reactions. In addition, the commonly observed side product
in the Michaelis–Arbuzov rearrangement, phosphonate 6, resulting from
reaction of triethylphosphite with the ethyl halide eliminated from the
reaction intermediate, was not detected in any case. This is surprising
since the typical synthesis of alkyl phosphonates by the Michaelis–
Arbuzov rearrangement, requires a 5-fold excess of alkyl halide to retard
7
the formation of phosphonate 6. Unfortunately, using a domestic micro-
wave oven it is difficult to obtain useful data to determine the basis for these
effects, as well as those seen in the synthesis of the phosphonium salts.

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However, future investigations to more precisely examine these effects are
planned once appropriate microwave equipment is available to conduct the
experiments.
In conclusion, it has been demonstrated that hydrogenations vessels
with threaded Teflon caps are a useful alternative to pressure tubes for
moderate scale syntheses in domestic microwave ovens. In addition,
moderate scale syntheses of organophosphorus reagents used in olefin
formation have been accomplished showing increased yields and shorter
reactions times using this procedure.
EXPERIMENTAL
All reactions were conducted in a domestic microwave oven
Panasonic) at 2450 MHz on high power (1100 Watt). The threaded hydro-
(
genation vessel and cap were purchased from Ace Glass and had a capacity
of approximately 200 mL, but reaction volumes were never allowed to
exceed 70 mL. All reagents were purchased from Aldrich Chemical Co,
and used without further purification. All products are known compounds
1
13
31
and were characterized by comparison of their H, C, and P NMR data
with those of authentic samples.
Caution! It is hazardous to rapidly heat organic reactions in closed
vessels by either conventional means or with microwave irradiation.
Therefore, caution should be exercised when conducting reactions of this type.
General Procedure for the Synthesis of Phosphonium Salts. Organic
halide (0.05 mol) and triphenylphosphine (0.05 mol) were added neat, or
dissolved in 60 ml of xylene as appropriate, and added to the hydrogenation
vessel with a threaded Teflon cap. The threaded cap on the hydrogenation
vessel was sealed finger tight and placed in a crystallizing dish surrounded
by glass wool. The glass wool not only serves to evenly heat the vessel, but
to absorb the reaction mixture if the vessel were to shatter. The vessel
and crystallizing dish are then placed in the microwave oven (Panasonic)
and heated for the appropriate time on high power (1100 Watt). Once
the heating cycle is complete and the crystallizing dish and vessel have
cooled to ambient temperature, the vessel is opened and the phosphonium
salts are removed and purified by recrystallization from an appropriate
solvent.
General Procedure for the Synthesis of Phosphonates. Organic halide
0.20 mol) and triethyl phosphite (0.20 mol) were added neat to the hydro-
(
genation vessel and the threaded Teflon cap was sealed finger tight.
The hydrogenation vessel was then placed in a crystallizing dish
and surrounded by glass wool. The glass wool not only serves to evenly

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ORGANOPHOSPHORUS CHEMISTRY. III
3381
heat the vessel, but to absorb the reaction mixture if the vessel were to
shatter. The vessel and crystallizing dish are then placed in the microwave
oven and heated for the appropriate time on high power (1100 Watt).
Once the heating cycle is complete and the crystallizing dish and
vessel have cooled to ambient temperature, the vessel is opened and the
mixture purified by fractional distillation or rotary evaporation as
necessary.
ꢀ
8
Methyltriphenylphosphonium iodide (3a): mp 228–231 C, Lit mp
ꢀ
13
1
2
3
1
30–234 C. H NMR d: 7.83–7.76 (m, 6H), 7.72–7.67 (m, 4H), 3.33 (d,
H, J ¼ 13.3). C NMR d: 135.01 (d, J ¼ 3.0 Hz), 133.13 (d, J ¼ 10.7 Hz),
30.32 (d, J ¼ 12.9 Hz), 118.92 (d, J ¼ 88.7 Hz), 10.76 (d, J ¼ 57.0 Hz).
3
1
P NMR d: 21.5.
ꢀ
(
Ethoxycarbonylmethyl)triphenylphosphonium bromide (3b): mp 153 C
ꢀ
4
1
(
(
4
dec), Lit mp 151 C (dec). H NMR d: 7.95–7.88 (5H, m), 7.82–7.77
3H, m), 7.71–7.64 (5H, m), 7.35–7.28(2H, m), 5.58(2H, d, J ¼ 13.8Hz),
1
3
.04 (2H, q, J ¼ 7.1 Hz), 1.07 (3H, t, J ¼ 7.2). C NMR d: 164.39 (d,
J ¼ 3.5 Hz), 135.16 (d, J ¼ 2.9 Hz), 133.95 (d, J ¼ 10.6 Hz), 130.25 (d,
J ¼ 13.1 Hz), 117.91 (d, J ¼ 89.0 Hz), 62.83, 33.18 (d, J ¼ 56.3 Hz), 13.71.
3
1
P NMR d: 20.7.
Benzyltriphenylphosphonium bromide (3c): mp 283–285 C, Lit mp
ꢀ
4
ꢀ
1
2
87–291 C. H NMR d: 7.79–7.71 (8H, m), 7.67–7.60 (5H, m), 7.41–7.29
(
2H, m), 7.25–7.20 (1H, m), 7.14–7.08(4H, m), 5.40 (2H, d, J ¼ 14.4 Hz).
1
3
C NMR d: 134.96 (d, J ¼ 2.9 Hz), 134.35 (d, J ¼ 9.9 Hz), 131.47 (d,
J ¼ 5.7 Hz), 130.11 (d, J ¼ 12.5 Hz), 128.78 (d, J ¼ 3.5 Hz), 128.36
d, J ¼ 3.9 Hz), 127.08(d, J ¼ 8.6 Hz), 117.75 (d, J ¼ 85.8 Hz), 30.83 (d,
(
3
1
J ¼ 46.8Hz). P NMR d: 23.0.
ꢀ
9
ꢀ
1
Diethyl methylphosphonate (5a): bp 190 C, Lit bp 194 C. H NMR d:
1
3
4
6
.10 (m, 4H), 1.46 (d, 3H, J ¼ 17.6 Hz), 1.33 (t, 6H, J ¼ 7.1 Hz). C NMR d:
3
1
1.14 (d, J ¼ 6.3 Hz), 16.10 (d, J ¼ 6.3 Hz), 10.88 (d, J ¼ 144.2 Hz). P NMR
d: 30.3.
ꢀ
9
Triethyl phosphonoacetate (5b): bp 174–176 C, (20 mmHg), Lit bp
1
1
1
(
(
42–145 (9 mmHg). H NMR d: 4.18(m, 6H), 2.97 (d, 2H, J ¼ 21.6 Hz),
1
3
.35 (t, 6H, J ¼ 7.1 Hz), 1.29 (t, 3H, J ¼ 6.1 Hz). C NMR d: 165.51
d, J ¼ 5.9 Hz), 62.37 (d, J ¼ 6.3 Hz), 61.25, 34.07 (d, J ¼ 134.2 Hz), 16.04
3
1
d, J ¼ 6.2 Hz), 13.81. P NMR d: 19.7.
ꢀ
9
Diethyl benzylphosphonate (5c): bp 168–170 C (20 mmHg), Lit bp
1
1
06–108(1 mmHg). H NMR d: 7.35 (m, 5H), 4.03 (m, 4H), 3.15 (d, 2H,
1
3
J ¼ 21.6 Hz), 1.23 (t, 6H, J ¼ 7.0 Hz). C NMR d: 131.34 (d, J ¼ 9.1 Hz),
1
29.51 (d, J ¼ 6.5 Hz), 128.25 (d, J ¼ 3.0 Hz), 126.59 (d, J ¼ 3.5 Hz), 61.83
3
1
(
d, J ¼ 6.8Hz), 33.49 (d, J ¼ 138.0 Hz), 16.10 (d, J ¼ 5.9 Hz). P NMR
d: 26.3.

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ACKNOWLEDGMENTS
The author wishes to thank the North Carolina Biotechnology Center
Institutional Development Grant Program (9610-IDG-1009) for the
purchase of the Bruker 400 MHz NMR used in this study.
REFERENCES
1
2
. (a) Gedye, R.; Smith, F.; Westaway, K.; Humera, A.; Baldisera, L.;
Laberge, L.; Roussel, J. Tetrahedron Lett. 1986, 27, 279. (b) Giguere,
R.J.; Bray, T.L.; Duncan, S.M.; Majetich, G. Tetrahedron Lett. 1986,
27, 4945.
. For reviews see: (a) Majetich, G.; Wheless, K. In Microwave-Enhanced
Chemistry Fundamentals, Sample Preparation, and Applications,
Kingston, H.M.; Haswell, S.J. Eds.; American Chemical Society,
Washington DC, 1997, pp. 455. (b) Caddick, S. Tetrahedron 1995, 51,
1
0403.
. Kiddle, J.J.; Gurley, A.F. Phosphorus, Sulfur, Silicon Relat. Elem.
000, 160, 195.
3
2
4. Kiddle, J.J. Tetrahedron Lett. 2000, 41, 1339.
5. Reinhold, G.; Guerin, M.; Kiddle, J.J. unpublished results.
6. Baghurst, D.R.; Mingos, D.M.P. J. Chem. Soc. Dalton Trans.
1992, 1151.
7
8
9
. Engel, R. Synthesis of Carbon-Phosphorus Bonds, CRC Press, Boca
Raton, FL, 1988.
. Vogal, A.I. Textbook of Practical Organic Chemistry, 5th Ed.;
Longmann, Harlow, 1989, p. 498.
. Bhattacharya, A.K.; Thyagarajan, G. Chem. Rev. 1981, 81, 415 and
references cited therein.
Received in the USA January 21, 2001

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