A high yielding, reproducible synthesis of trimethylsilylketene

Article abstract of DOI:10.1081/SCC-120004861

A two-step sequence for the preparation of trimethylsilylketene, from chloroacetaldehyde diethyl acetal via ethoxyacetylene, has been modified and optimized.

Full text of DOI:10.1081/SCC-120004861

This article was downloaded by: [Pennsylvania State University]
On: 04 October 2013, At: 07:43
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A HIGH YIELDING, REPRODUCIBLE SYNTHESIS OF
TRIMETHYLSILYLKETENE
a
a
a
a
T. Howard Black , John R. Farrell , Donald A. Probst & Michael C. Zotz
a
Department of Chemistry, Eastern Illinois University, Charleston, IL, 61920, U.S.A.
Published online: 16 Aug 2006.
To cite this article: T. Howard Black , John R. Farrell , Donald A. Probst & Michael C. Zotz (2002) A HIGH YIELDING,
REPRODUCIBLE SYNTHESIS OF TRIMETHYLSILYLKETENE, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:13, 2083-2088, DOI: 10.1081/SCC-120004861
To link to this article: http://dx.doi.org/10.1081/SCC-120004861
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 32(13), 2083–2088 (2002)
A HIGH YIELDING, REPRODUCIBLE
SYNTHESIS OF
TRIMETHYLSILYLKETENE
T. Howard Black,* John R. Farrell, Donald A. Probst,
and Michael C. Zotz
Department of Chemistry, Eastern Illinois University,
Charleston, IL 61920, USA
ABSTRACT
A two-step sequence for the preparation of trimethylsilyl-
ketene, from chloroacetaldehyde diethyl acetal via ethoxy-
acetylene, has been modified and optimized.
INTRODUCTION
Silyl ketenes are unique in their chemical behavior, when contrasted
with their alkyl or aryl counterparts. One of their most valuable attributes is
their extraordinary stability, such that they can be stored for extended
periods in a refrigerator without the tendency to dimerize so prevalent
with other types of ketenes. Trimethylsilylketene (TMSK), the prototypical
member of this family, enjoys a wide diversity of implementations in
synthetic chemistry, encompassing organic, organometallic, and inorganic
applications.
*
Corresponding author. E-mail: cthb@eiu.edu
083
2
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

2
084
BLACK ET AL.
The procedure reported herein is an adaptation of the method
[1]
described by Ruden. Although several other procedures for the synthesis
[
2]
of TMSK have been published (and have been tested by this research
group), we have found our modification of the Ruden method to be, by
far, the most consistently high-yielding and reproducible. The formation of
TMSK from ethoxyacetylene (which is the last step of the two-step Ruden
[
3]
13
protocol) has recently been subjected to a theoretical study. Also, the C,
7
1
29
O, and Si NMR spectra and theoretical explanation for the stability of
[
4]
TMSK, in addition to other silylated ketenes, have been published.
The utility of TMSK up to 1995 is well-documented in Danheiser’s
excellent, concise review. Its utility has continued to expand in the inter-
vening years. For instance, TMSK reacts with acyl isocyanates to yield
2-pyridones; a theoretical study of this reaction has also been carried
out.
reagents, which have then been exploited to form isoquinolines via electro-
cyclization. ꢀ,N-Diarylnitrones react with TMSK to provide oxindoles
in good yield. In the organometallic area, TMSK was used quite recently
in carbonyl coupling reactions to prepare functionalized iron ketene
complexes.
Silyl enol ethers are well known and commonly employed in organic
synthesis; there is now a facile preparation of silyl ynol ethers via the reac-
tion of ynolate anions derived from silylketenes with electrophiles. ꢀ-Silyl
ketones are easily synthesized from the reaction of silyl ketenes with carban-
[4]
[5]
[6]
It also forms ketenimines, via treatment with certain Wittig
[7]
[8]
[9]
[10]
[
11]
[
12]
ions, using organocerium reagents.
Finally, TMSK undergoes facile [2 þ 2] cycloaddition with aldehydes,
with the ensuing trimethylsilyl ꢁ-lactones serving as versatile synthetic inter-
[
13]
mediates.
spiroketals,
rated carboxylic acids via a nonbasic alternative to the Wittig reaction.
The synthesis and chemistry of chiral silyl ꢁ-lactones are covered in Romo’s
For instance, they have been converted into monoanomeric
[14]
[15]
the hypocholesterolemic agent 1233A,
and ꢀ,ꢁ-unsatu-
[
16]
[17]
excellent recent review.
DISCUSSION
The two-step protocol is outlined in Scheme 1 below. Step A involves
the double elimination of chloroacetaldehyde diethyl acetal (1) via treatment
ꢀ
with sodium amide in liquid ammonia. Petroleum ether (b.p. 90–110 C) was
added, and the liquid ammonia allowed to evaporate overnight, leaving
the bright yellow sodium salt of ethoxyacetylene (2) adhering to the side
of the flask. A large quantity of ice was added quickly, with vigorous
stirring/swirling, to protonate the salt. This is a very exothermic reaction,

TRIMETHYLSILYLKETENE
2085
Scheme 1.
and the cooling is necessary to prevent loss of any product, which is quite
volatile. The crude ethoxyacetylene 2 was then isolated through extraction.
After being dried over magnesium sulfate, the solution was subjected to
fractional distillation, affording pure product in 65% yield.
In step B, the ethoxyacetylene (2) was deprotonated via treatment with
ꢀ
methyllithium at 0 C in ether solution, whereupon a very slight excess of
chlorotrimethylsilane was slowly added. The mixture was stirred at room
temperature for 12 h, acquiring a light yellow color, and was then filtered
through a medium frit glass funnel. The resulting yellow filtrate was con-
centrated in vacuo to afford ethoxytrimethylsilylacetylene as a clear yellow
oil, which was then distilled under reduced pressure (ca. 20 mm). The acti-
vation energy for the rearrangement leading to TMSK is quite high, in that
ꢀ
the pot temperature must reach 125–135 C before distillation commences.
ꢀ
The product distills at 75–82 C in yields from 50–70%.
EXPERIMENTAL SECTION
Ethoxyacetylene (2): To a 2 L 3-neck round bottom flask equipped
with a condenser, gas inlet, and rubber septum was added 0.2 g FeNO3
9
H O. The flask was submerged in a methanol/liquid nitrogen bath,
2
ꢀ
cooled to ca. À 80 C, and filled with approximately 1 L of anhydrous
liquid ammonia. Sodium (46 g, 2 mol) was then added in small portions
over a two minute period. The solution was allowed to stir at À 80 C for
ꢀ
90 min, at which point 0.2 g FeNO 9H O was added and the solution stirred
an additional 30 min. Next, 79.95 mL (81.4 g, 0.533 mol) of chloroacetalde-
3 2
hyde diethyl acetal (1) was added dropwise at a rate of ca. 1 mL/min.
ꢀ
The solution was allowed to stir at À 80 C for 30 min, then the bath was
ꢀ
removed and 200 mL of petroleum ether (bp 90–110 C) was added. The
solution was allowed to stir overnight to let the ammonia evaporate.

2
086
BLACK ET AL.
When the ammonia was gone, ca. 400 g of ice was added over 1 min,
and the flask was swirled until all of the solid had been dissolved from
the sides.
CAUTION: This is an exothermic reaction, and some product will be
lost if the flask becomes too warm. Next, both phases were transferred to a
separatory funnel and separated. The aqueous layer was extracted with four
ꢀ
5
0 mL portions of petroleum ether (bp 90–110 C). The combined organic
layers were washed with ice cold water and dried over anhydrous magne-
sium sulfate. The drying agent was removed via gravity filtration, the filtrate
was placed in a 1 L flask, and the ethoxyacetylene was distilled off at atmos-
pheric pressure. Purification was achieved via fractional distillation through
a 15 cm Vigreaux column to yield ethoxyacetylene in 65% yield (b.p.
ꢀ
[18]
ꢀ
5
0–51 C/760 mm Hg; lit. 49–51 C/749 mm Hg). The following additional
1
analytical data were collected: H-NMR dCDCl3: 1.348 (3H, t), 1.498 (1H, s),
4
.09 (2H, q) ppm (Lit. 1.37 (3H, t), 1.53 (1H, s), 4.23 (2H, q) ppm).
1
3
C-NMR d
960, 2140 cm (Lit. 3300, 2140 cm ).
: 14.08, 26.34, 74.49, 90.69 ppm. IR (neat) nmax: 3320,
CDCl3
À1
[19]
À1
2
Trimethylsilylketene (3): An oven dried 500 mL 2-necked round
bottom flask equipped with a rubber septum, nitrogen inlet and magnetic
stir bar was cooled under a continuous stream of nitrogen. The flask was
ꢀ
cooled to 0 C, whereupon 250 mL of anhydrous ether and 8.3 g
(
118.4 mmol) of ethoxyacetylene were added to the reaction vessel. To
the resulting mixture was added 88 mL of a 1.4 M solution (123 mmol)
of methyllithium in ether, dropwise via syringe, over 30 min. After this
period, 15.3 mL of freshly distilled (over CaH ) chlorotrimethylsilane
2
(
13.1 g, 120 mmol) was added, dropwise via syringe, over 15 min. During
this addition, a white precipitate was observed to form. After the addition
was complete, the mixture was allowed to stir at ambient temperature
overnight.
The following morning, the reaction mixture was carefully filtered
through a (medium) sintered glass funnel and the filter cake washed with
a small quantity of anhydrous ether. The reaction mixture was then trans-
ferred to a one neck 500 mL round bottom flask and the ether gradually
[
20]
removed via simple distillation at low heat.
the ether, the pot temperature was gradually increased to 120 C and the
Upon complete removal of
ꢀ
ꢀ
[1]
desired ketene was collected at 75–82 C/760 mm Hg (lit.
ꢀ
b.p.
1–82 C/760 mm Hg). Typical yields of pure trimethylsilylketene, using
8
this procedure, range between 50 and 70%. The following additional ana-
1
lytical data were collected: H-NMR dCDCl3: 1.719 (1H, s), 0.122 (9H, s) ppm
[
21]
(
Lit. dCCl4: 1.65 (s, 1H, HC¼C¼O), 0.12 (s, 9H, (CH ) Si) ppm);
CDCl3 CDCl
3
3 3
1
3
[21]
C-NMR d
(300 MHz): 179.264, 0.373, À 0.211 ppm (Lit.
d
(
50.3 MHz): 179.45 (C¼C¼O), 0.54 ((CH ) Si), À 0.25 (C¼C¼O) ppm; IR
3
3

TRIMETHYLSILYLKETENE
2087
À1
[21]
(
(
neat) nmax: 3340, 3020, 2940, 2100, 1260, 1240, 1040, 840 cm (Lit.
À1
CCl ) 3050, 2980, 2130, 1280, 1260, 1060, 860, 630 cm ).
4
ACKNOWLEDGMENTS
We gratefully thank the National Institutes of Health (R15-GM52677-
1), the Research Corporation, and the Council for Faculty Research of
0
Eastern Illinois University, for their generous support of this work.
REFERENCES
1
2
. Ruden, R.A. J. Org. Chem. 1974, 39, 3607.
. Loebach, J.L.; Danheiser, R.L. Trimethylsilylketene, in the
Encyclopedia of Reagents for Organic Synthesis, Paquette, L.A., Ed. -
in-Chief; Wiley: W. Sussex, England (1995); pp. 5266-8 and Numerous
References Cited Therein.
3
4
. Oblin, M.; Rajzmann, M.; Pons, J.-M, Tetrahedron 1997, 53, 8165.
. Allen, A.D.; Egle, I.; Janoschek, R.; Liu, H.W.; Ma, J.; Marra, R.;
Tidwell, T.T. Chem. Lett. 1996, 45.
5
6
7
. Takaoka, K.; Aoyama, T.; Shiori, T. Tetrahedron Lett. 1996, 37, 4973,
4
977.
. Matsumoto, T.; Takaoka, K.; Aoyama, T.; Shiori, T. Tetrahedron
997, 53, 225.
1
. Barbaro, G.; Battaglia, A.; Giorgianni, P.; Guerrini, A.; Seconi, G. J.
Org. Chem. 1995, 60, 6032.
8
9
. Molina, P.; Vidal, A.; Tovar, F. Synthesis 1997, 963.
. Takaoka, K.; Aoyama, T.; Shioiri, T. Tetrahedron Lett. 1999, 40,
3017.
1
1
1
1
0. Kandler, H.; Bidell, W.; Janicke, M.; Knickmeier, M.; Veghini, D.;
Berke, H. Organometallics 1998, 17, 960.
1. Akai, S.; Kitagaki, S.; Naka, T.; Yamamoto, K.; Tsuzuki, Y.;
Matsumoto, K.; Kita, Y. J. Chem. Soc., Perkin Trans. 1 1996, 1705.
2. Akai, S.; Kitagaki, S.; Matsuda, S.; Tsuzuki, Y.; Naka, T.; Kita, Y.
Chem. Pharm. Bull. 1997, 45, 1135.
3. Black, T.H. ꢁ-Lactones as Useful Synthetic Intermediates. In Trends in
Heterocyclic Chemistry, Menon, J., Ed.; Research Trends:
Trivandrum, 1993; Vol. 3, 275, publ. 1995.
1
1
4. Zemribo, R.; Mead, K.T. Tetrahedron Lett. 1998, 39, 3891.
5. Dymock, B.W.; Kocienski, P.J.; Pons, J.-M. Synthesis 1998, 1655.

2
088
BLACK ET AL.
1
1
1
6. Black, T.H.; Zhang, Y.; Huang.; J.; Smith, D.C.; Yates, B.E. Synth.
Commun. 1995, 21, 15.
7. Yang, H.W.; Romo, D. Tetrahedron 1999, 55, 6403 and References
cited therein.
8. Jones, E.R.H.; Eglinton, G.; Whiting, M.C.; Shaw, B.L. Org. Synth.
1963, Coll. Vol. IV, 404.
19. McCarney, C.C.; Ward, R.S. Tetrahedron 1976, 32, 1189.
20. It is Best to Employ an Oil Bath for the Heating Element.
21. Valenti, E.; Pericas, M.A.; Serratosa, F. J. Org. Chem. 1990, 55, 395.
Received in the USA July 24, 2001