Falling-solid flash vacuum pyrolysis: An efficient preparation of arylacetylenes

Article abstract of DOI:10.1002/anie.201412431

Automated falling-solid flash vacuum pyrolysis allows the rapid and efficient synthesis of a variety of arylacetylenes from 4-arylmethylidene-5(4H)-isoxazolone derivatives, which were prepared from aldehyde precursors. The acetylenes are readily obtained in multigram quantities. Taking the heat: Unlike in flash vacuum pyrolysis, involatile compounds can be used in falling-solid flash vacuum pyrolysis (FS-FVP). This method is employed for the rapid and efficient synthesis of a variety of arylacetylenes from 4-arylmethylidene-5(4H)-isoxazolones, which were in turn prepared from aldehyde precursors.

Full text of DOI:10.1002/anie.201412431

Angewandte
Chemie
DOI: 10.1002/anie.201412431
Synthetic Methods
Falling-Solid Flash Vacuum Pyrolysis: An Efficient Preparation of
Arylacetylenes**
Curt Wentrup,* Jꢀrgen Becker, and Hans-Wilhelm Winter
Dedicated to Professor Fritz Vçgtle on the occasion of his 75th birthday
Abstract: Automated falling-solid flash vacuum pyrolysis
allows the rapid and efficient synthesis of a variety of
arylacetylenes from 4-arylmethylidene-5(4H)-isoxazolone
derivatives, which were prepared from aldehyde precursors.
The acetylenes are readily obtained in multigram quantities.
material is added in a continuous manner to a vertical
pyrolysis tube under high vacuum (Figure 1). The crucial and
innovative centerpiece is the spinning brush (E), which
permits the controlled addition of the starting material into
the vertical pyrolysis tube as a steady spray of powdered solid.
Commercially available, tight-fitting spiral bottle brushes
with nylon 6,6 bristles work very well. The amount of sample
per unit time is easily controlled by the velocity of the
spinning brush. To prevent the solid from falling through the
tube unchanged, a fine plug of quartz wool is suspended on
top of a quartz cross in the center of the pyrolysis tube.
[
1]
T
(
he popularity of click chemistry has sparked renewed
interest in the synthesis of acetylenes. Flash vacuum pyrolysis
FVP) of 4-methyleneisoxazol-5(4H)-ones 1, readily synthe-
sized from 3-methylisoxazolone and aldehydes, gives access to
[2]
a variety of alkynes 3 in high yields (Scheme 1). Details of
the mechanism of the reaction have been investigated
[
3]
computationally, and it has been found to take place via
Scheme 1. Synthesis of acetylenes 3 by FVP of isoxazolones 1.
transient ethynylidenes 2, which by 1,2-hydrogen migration
afford the acetylenes 3. This reaction and its reverse, the
acetylene–vinylidene rearrangement, are of considerable
[
4]
theoretical interest. Analogous FVP of 4-aminomethylene-
isoxazolones allowed the generation and characterization of
ethynylamines RR’NÀCꢀCÀH and RNHÀCꢀCÀH and
[
5]
ketenimines RÀN=C=CH .
2
However, numerous compounds are too involatile for
conventional FVP. For this reason, various methods such as
solvent-spray and solid-pyrolysis procedures have been
employed. We have developed a fully automated, convenient,
controllable, and rapid falling-solid flash vacuum pyrolysis
[6,7]
[8]
[9]
(
FS-FVP), in which the finely powdered, solid starting
[*] Prof. Dr. C. Wentrup
School of Chemistry and Molecular Biosciences
The University of Queensland
Brisbane, Qld 4072 (Australia)
E-mail: wentrup@uq.edu.au
Figure 1. Automated apparatus for falling-solid flash vacuum pyrolysis
(FS-FVP). A) spinning-band motor; B) magnetic coupling; C) sample
refill port; D) sample compartment; E) tight-fitting rotating brush
attached to drive shaft above; F) water-cooled mantle; G) electrical
pyrolysis oven housing a 30ꢀ2 cm quartz pyrolysis tube; H) quartz
wool supported on a quartz rod ending with a cross and standing in
the cold trap; I) cold trap; J) connection to second cold trap and high
vacuum system. The sample is placed on top of the brush E before
applying vacuum and starting the operation. A pressure-equalizing
side tube connects the top and bottom of the sample and brush
compartments (not shown).
Prof. Dr. C. Wentrup, Dr. J. Becker, Dr. H.-W. Winter
Fachbereich Chemie der Philipps-Universitꢁt
35037 Marburg (Germany)
[
**] This work was supported by the Deutsche Forschungsgemeinschaft,
the Fonds der Chemischen Industrie, and the Australian Research
Council.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201412431.
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Alternatively, if the pyrolysis tube is held slightly nonverti-
cally, the solid will fall and volatilize on the hot wall. To
minimize vacuum fluctuations, it is preferable to insert an 8 L
isolated from this reaction in 12% yield together with a trace
of benz[a]azulene.
For a further proof of principle, 1,4-diethynylbenzene (15)
was prepared in 72% yield by falling-solid FVP of the highly
involatile 1,4-phenylenebis(methyleneisoxazolone) (14) at
7508C (Scheme 3).
(
or larger) vacuum ballast in the high-vacuum pumping line.
We report herein the employment of this apparatus in the
synthesis of acetylenes. Other examples will be summarized
below.
The isoxazolone starting materials 6 described below are
too involatile for efficient FVP under conventional condi-
tions. In contrast, the falling-solid pyrolysis is rapid, can be
conducted easily on a multigram scale, and generally affords
high yields. Being a continuous flow method, it is possible to
scale up the reaction to much larger quantities. Employing
this technique, we have prepared several tens of grams of
acetylenes. The isoxazolones 6 (Scheme 2) were synthesized
from 3-methylisoxazolone (4) and the appropriate aldehyde 5
Scheme 3. Preparation of 1,4-diethynylbenzene (15) by FS-FVP.
We have used the same method to synthesize a variety of
aryl- and heteroarylacetylenes prepared previously by con-
[
2]
using a previously reported procedure.
The synthesis of the p-nitrobenzylidene isoxazolone 9
took an unexpected course. In fact, the product of reaction of
[2]
ventional FVP. The great advantage of the FS-FVP method
is that multigram quantities can be obtained in a few hours.
For the reactions shown in Scheme 2 and 3, the falling-solid
method is far superior.
3
-methylisoxazolone (4) with p-nitrobenzaldehyde was the
bis(isoxazolyl)methane derivative 8, which is far too involatile
for conventional FVP. However, falling-solid pyrolysis of 8 at
The falling-solid pyrolysis method is advantageous in
many other applications. For example, 5-substituted tetra-
zoles are convenient and safe starting materials for the
7
508C afforded 10 in 71% yield (Scheme 2). During the
course of this reaction 3-methylisoxazolone (4) is eliminated,
thus generating 9, which subsequently undergoes pyrolysis to
form 10. The eliminated 3-methylisoxazolone undergoes
pyrolysis to form 2-methyl-1-azirine, as we have described
[
11]
pyrolytic generation of arylcarbenes, but they are often too
involatile to be practical. Here, we have used FS-FVP to
generate the 4- and 3-quinolylcarbenes 16 and 17 (Scheme 4).
Both carbenes undergo rearrangement to form 2-quinolyl-
carbene (18; also generated from the tetrazole) and then to 1-
naphthylnitrene (19), which finally undergoes ring contrac-
tion to form 1-cyanoindene and then 3- and 2-cyanoindenes.
Similarly, both the tetrazole and the aldehyde tosylhydrazone
sodium salt have been used to generate 1-azulenylcarbene
(20), which rearranges to form cyclobuta[de]naphthalene (21)
and cyclopenta[cd]indene (22; Scheme 5).
[10]
for the analogous formation of 2-phenyl-1-azirine,
but
under these reaction conditions the azirine decomposes to
form HCN and ethene.
Similarly, 2-phenylbenzaldehyde reacted with two molec-
ules of 3-methylisoxazolone (4) to yield compound 11.
Falling-solid pyrolysis of 11 at 7008C afforded 2-biphenyl-
[
4]
ylacetylene (13) in 65% yield. Phenanthrene was also
Experimental details of these reactions
and elucidation of the reaction mecha-
nisms will be published elsewhere.
Although the thermal decomposition of
tosylhydrazone salts has been employed
for the generation of volatile diazo com-
pounds, this method fails or else affords
only very poor yields for compounds with
more than about ten heavy atoms. This is
a result of decreased volatility, which
results in uncontrolled decomposition of
the diazo compounds under conventional
FVP conditions.
In conclusion, falling-solid flash
vacuum pyrolysis enables the use of invo-
latile starting materials in FVP reactions.
Applied to 4-arylmethyleneisoxazolone
starting materials, it is an extremely
useful technique for the gram-scale
preparation of arylacetylenes.
Scheme 2. Aryl acetylenes prepared by falling-solid flash vacuum pyrolysis (FS-FVP).
Preparative yields on a 1–5 g scale are given (%).
2
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À3
À1
1
0 –10 hPa. After the pyrolysis, CO2 and acetonitrile were
removed under vacuum, and the product was isolated from the cold
trap by dissolution (e.g. in CH Cl ) or distillation.
2
2
Received: December 28, 2014
Revised: January 26, 2015
Published online: && &&, &&&&
Keywords: alkynes · arenes · flash pyrolysis · rearrangement ·
.
synthetic methods
[
1] For reviews on click chemistry, see: a) H. C. Kolb, M. G. Finn,
K. B. Sharpless, Angew. Chem. Int. Ed. 2001, 40, 2004; Angew.
Chem. 2001, 113, 2056; b) M. Meldal, C. W. Tornøe, Chem. Rev.
2
3
008, 108, 2952; c) M. G. Finn, V. V. Fokin, Chem. Soc. Rev. 2010,
9, 1231, and subsequent papers in this themed issue.
Scheme 4. Generation of quinolylcarbenes by FS-FVP of tetrazoles.
[
2] C. Wentrup, H.-W. Winter, Angew. Chem. Int. Ed. Engl. 1978, 17,
09; Angew. Chem. 1978, 90, 643.
6
[3] H. S. Rzepa, C. Wentrup, J. Org. Chem. 2013, 78, 7565.
[4] I. D. Mackie, R. P. Johnson, J. Org. Chem. 2009, 74, 499.
[5] a) H.-W. Winter, C. Wentrup, Angew. Chem. Int. Ed. Engl. 1980,
19, 720; Angew. Chem. 1980, 92, 743; b) C. Wentrup, H. Briehl, P.
Lorencak, U. J. Vogelbacher, H.-W. Winter, A. Maquestiau, R.
Flammang, J. Am. Chem. Soc. 1988, 110, 1337.
[
6] For FVP reviews, see: a) R. F. C. Brown, Pyrolytic Methods in
Organic Chemistry, Academic Press, New York, 1980; b) U. E.
Wiersum, Recl. Trav. Chim. Pays-Bas 1982, 101, 317; c) U. E.
Wiersum, Recl. Trav. Chim. Pays-Bas 1982, 101, 365; d) M.
Karpf, Angew. Chem. Int. Ed. Engl. 1986, 25, 414; Angew. Chem.
1
986, 98, 413.
Scheme 5. Generation of 1-azulenylcarbene (20) by FS-FVP of the
tetrazole and aldehyde tosylhydrazone sodium salt.
[
[
7] For a review, see: C. Wentrup, Aust. J. Chem. 2014, 67, 1150.
8] a) O. Meth-Cohn, Acc. Chem. Res. 1987, 20, 18; b) Y. Rubin, S. S.
Lin, C. B. Knobler, J. Anthony, A. M. Boldi, F. Diederich, J. Am.
Chem. Soc. 1991, 113, 6943.
[9] a) F. Vçgtle, P. Fornell, W. Lçhr, Chem. Ind. 1979, 416; b) F.
Vçgtle, L. Rossa, Angew. Chem. Int. Ed. Engl. 1979, 18, 515;
Angew. Chem. 1979, 91, 534.
[10] D. Bꢀguꢀ, A. Dargelos, H. M. Berstermann, K. P. Netsch, P.
Bednarek, C. Wentrup, J. Org. Chem. 2014, 79, 1247.
[11] D. Kvaskoff, H. Lꢁerssen, P. Bednarek, C. Wentrup, J. Am.
Chem. Soc. 2014, 136, 15203.
Experimental Section
Standard procedure for the preparation of arylacetylenes by falling-
solid flash vacuum pyrolysis: The relevant isoxazolone (2.0 g) was
loaded on top of the tight-fitting brush in the falling-solid pyrolysis
apparatus. Upon application of the vacuum, the pyrolysis oven was
brought to the required temperature (typically 7508C). The cold trap
was immersed in liquid N2 (employing usually two cold traps in
series). The spinning-band motor was started, and the pyrolysis took
place over the course of 2.5 h, typically at a dynamic pressure of
Angew. Chem. Int. Ed. 2015, 54, 1 – 4
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
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Angewandte
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Communications
Synthetic Methods
C. Wentrup,* J. Becker,
H.-W. Winter
&&&& — &&&&
Falling-Solid Flash Vacuum Pyrolysis: An
Efficient Preparation of Arylacetylenes
Taking the heat: Unlike in flash vacuum
pyrolysis, involatile compounds can be
used in falling-solid flash vacuum pyrol-
ysis (FS-FVP). This method is employed
for the rapid and efficient synthesis of
a variety of arylacetylenes from 4-aryl-
methylidene-5(4H)-isoxazolones, which
were in turn prepared from aldehyde
precursors.
4
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 4
These are not the final page numbers!