Deprotection of acetals from unsaturated, unstable bromoketones

Article abstract of DOI:10.1080/00397911.2013.821133

The unstable ketones 1-bromo-3-buten-2-one, 1-bromo-3-butyn-2-one, and 1,3-dibromo-3-buten-2-one can be obtained from the corresponding acetals in high yields by treating the acetals with anhydrous iron (III) chloride suspended on dry silica. A simplified procedure for preparing the reagent is also given.

Full text of DOI:10.1080/00397911.2013.821133

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Deprotection of Acetals from
Unsaturated, Unstable Bromoketones
Alexandre Descomps a & Rolf Carlson a
a Department of Chemistry , University of Tromsø , Tromsø , Norway
Accepted author version posted online: 08 Nov 2013.Published
online: 20 Feb 2014.
To cite this article: Alexandre Descomps & Rolf Carlson (2014) Deprotection of Acetals from
Unsaturated, Unstable Bromoketones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 44:6, 757-761, DOI: 10.1080/00397911.2013.821133
To link to this article: http://dx.doi.org/10.1080/00397911.2013.821133
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Synthetic Communications1, 44: 757–761, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.821133
DEPROTECTION OF ACETALS FROM UNSATURATED,
UNSTABLE BROMOKETONES
Alexandre Descomps and Rolf Carlson
Department of Chemistry, University of Tromsø, Tromsø, Norway
GRAPHICAL ABSTRACT
Abstract The unstable ketones 1-bromo-3-buten-2-one, 1-bromo-3-butyn-2-one, and 1,3-
dibromo-3-buten-2-one can be obtained from the corresponding acetals in high yields by
treating the acetals with anhydrous iron (III) chloride suspended on dry silica. A simplified
procedure for preparing the reagent is also given.
Keywords Acetal deprotection; iron (III) chloride; silica; unsaturated bromoketones
INTRODUCTION
This article is complementary to previous communication[1–3] and describes a
simplified procedure for liberating unstable bromoketones from their corresponding
ethylene acetals. The prepared compounds are shown in Figure 1.
Received April 8, 2013.
Address correspondence to Rolf Carlson, Department of Chemistry, University of Tromsø,
NO-9037 Tromsø, Norway. E-mail: rolf.carlson@uit.no
757

758
A. DESCOMPS AND R. CARLSON
Figure 1. Compounds prepared.
The scope of using these compounds as building blocks in synthesis is not yet
fully explored. Reactions of 1 with nucleophilic reagents such as amines, complex
hydrides, and stabilized carbanions is described in Westerlund et al.[1] The reaction
of 3 with stabilized carbanions gave functionalized cyclopentenons by a conjugate
addition, dyhydrobromination, and an intramolecular displacement of the bromine
in the bromomethyl group.[2] To the best of our knowledge, the use of 2 in synthetic
transformations has not yet been reported.
The synthesis of 1-bromo-3-buten-2-one, 1, is described in Westerlund and
Carlson[3] and Carlson et al.,[4] and the final step is the deacetalization of the ketone.
Hydrolysis under acid conditions is inefficient. Formolysis with 98% formic acid
afforded the desired transformation in 86% yield. Hydrolysis with 1:1 mixtures of
Et2O=C5H12 and HCO2H=H2O under microwave activation was also efficient, and
afforded 74% yield. The formolytic conditions could also be used to liberate
1-bromo-3-butyn-2-one, 2, from the corresponding acetal in 74% yield. However,
any attempts to cleave the ethylene acetal, 6, from 1,3-dibromo-3-buten-2-one, 3,
failed, and this compound was instead obtained by dehydrobromination of
1,3,4-tribromo-2-butanone with lithium carbonate.[3] The yield was very low,
31%, mainly due to rapid polymerization of the unsaturated bromoketone (see
Scheme 1). An inefficient method for the synthesis of 3 by bromination of
2-trimethylsiliyloxy-1,3 butadiene has previously been described.[2]
Scheme 1. Synthetic route to 3.

DEPROTECTION OF ACETALS
759
Scheme 2. Bromoacetals deprotected by FeCl3 on dry silica.
We thought that the procedure for the synthesis of 3 could be improved if it
would be possible to cleave the acetal. A procedure for acetal cleavage by using iron
(III) chloride on silica has been published.[6] In the published procedure, the reagent
is prepared by adding ferric chloride dissolved in acetone to silica, followed by evap-
oration of the acetone under reduced pressure, then by drying in vacuum at room
temperature for several hours. The reagent has also been prepared by stirring silica
and iron (III) chloride for 24 h at room temperature.[7] We have found that the
reagent can be prepared more rapidly: Dry anhydrous iron (III) chloride is added
to dry silica followed by stirring of the mixture magnetically for 1 h on an ice-bath,
or for larger batches, by vigorous shaking of the mixture in a stoppered flask. The
reagent is a yellow powder and can be used directly for acetal cleavage (see the
Experimental for details). See Scheme 2.
The following results were obtained:
EXPERIMENTAL
General
Silica (SiO2-Davisil RLC14A 35–70, 35–70 mm) and iron (III) chloride
reagent grade 97% from Sigma-Aldrich were used. The bromoacetals were prepared
according to Mekonnen et al.[5] and Westerlund and Carlson.[3]
Preparation of the Silica-Iron (III) Chloride Reagent
A round-bottomed flame-dried 1 L flask was purged with nitrogen and then
charged with 100 g of dry silica and 10.0 g of iron (III) chloride. An egg-shaped,
60 mm magnetic stirring bar was introduced, and the mixture was magnetically
stirred on an ice-bath for 1 h.

760
A. DESCOMPS AND R. CARLSON
Warning! The bromoketones 1, 2, and 3 are very powerful lacrymators and can
also be expected to be mutagenic. They should be handled with great care.
Cleavage of the Acetals 4, 5, and 6
The actetal (10.00 g) was dispersed on 30 g of silica and added to the stirred
silica-iron (III) chloride reagent by means of a funnel. The mixture was then stirred at
ꢀ0 ꢁ for the time given in Scheme 2. Samples of the reaction mixture were withdrawn
and analyzed by GLC to ensure a complete conversion. Then, 400 mL of diethyl ether
was added, and the resulting heterogeneous mixture was filtered by suction through a
sintered glass funnel. The filter cake was washed twice with 100 mL portions of diethyl
ether. The combined etheral solutions were washed three times with 200 mL portions of
distilled water, and dried over anhydrous magnesium sulfate.
After filtration, ca. 10 mg of magnesium oxide and ca. 10 mg of hydroquinone
were added to prevent polymerization, and the ether was removed by evaporation
under reduced pressure from a room-temperature water bath. The pressure was
regulated to obtain a smooth distillation. Then, the receiver flask was emptied and
the evaporation was continued for 15 min at 10 mbar to remove traces of the diethyl
ether. The purity of the crude products were >95% (1H NMR), and they can be
taken to the next transformation without further purification. The following yields
were obtained:
2-Bromomethyl-2-vinyl-1,3-dioxolane, 4, gave 6.17–6.95 g (80–90%) of
1-bromo-3-buten-2-one, 1. The reaction time was 0.5 h.
2-Bromomethyl-2-ethynyl-1,3-dioxolane, 5, gave 5.76–6.15 g (75–80%) of
1-bromo-3-butyn-2-one, 2. The reaction time was 1 h.
2-Bromomethyl-2-(1-bromoethenyl)-1,3-dioxolane, 6, gave 6.17–6.95 g (80–90%)
of 1-bromo-3-buten-2-one, 3. The reaction time was 1.5 h.
The ketones undergo polymerization at room temperature, but they can be
stored for several days in the freezer. Ketone, 3, should be stored at ꢂ50 ꢁC.
GLC Analyses to Monitor the Reaction
Samples (ca. 100 mg) of the reaction mixture were withdrawn from the reaction
mixture with a spoon and transferred into a 2 mL vial. Water (0.5 mL) and diethy-
lether (1 mL) were added, and the mixture was shaken. The etheral layer was with-
drawn and filtered through a plug of cotton, and the volume was adjusted to 2 mL.
The analyses were made on a Varian 3300 chromatograph equipped with split injector
and a flame ionization detector. Specifications were as follows: column: SPB-5, 30 m,
0.35mm i.d. Injection volume 1 mL; injection temperatuꢂre1, 275 ꢁC; detector temperature,
275 ꢁC; temperature program: 70ꢁC, 5 min; 10 ꢁC min , 180ꢁC.
Spectroscopic Characterization of 1, 2, and 3
This was reproduced from Westerlund and Carlson[3] and Carlson et al.[4]
General. All 1H and 13C NMR spectra were recorded on a Varian 400
FT-NMR system using CDCl3 as a solvent at room temperature. Chemical shifts

DEPROTECTION OF ACETALS
761
are given in ppm and J-values in Hz. IR spectra were recorded on a FT-IR
spectrometer and are reported as wave number. GC-MS spectra were registered on
a Hewlett 5890 Packard series II CP Sil 5 CB column (25 m) followed by VG Quattro
mass spectrometer. A Finnigan-MAT-95XL mass spectrometer was used to obtain
HRMS data, and the spectra were obtained at 250 ꢁC and 70 eV.
1-Bromo-3-buten-2-one, 1. The product is unstable, and it was not possible
to send a sample for elemental analysis. Spectral properties are as follows:
1H NMR: d 4.03 (s, 2H), 5.95 (dd, 1H, J ¼ 10. 6 Hz, 0.9 Hz), 6.38 (dd. 1H, J ¼ 17.5 Hz,
Hz, 0.9 Hz), 6.55 (dd, 1H, J ¼ 17.5 Hz, 10.6 Hz); 13C NMR: d ¼ 32.6, 131.1, 133.2,
191.5; IR (neat between NaCl plates) nmax=cmꢂ1: 1690 (C O), 1620 (C C–C O);
MS (EI 70 eV): m=z (relative abundance) [Assignment] 150 (78) 148 (77) [Mþ],
123 (35), 121 (32) [M - vinyl], 95 (100), 93 (99) [CH2Brþ], 79, 69 (60) [M - Br], 55
(92) [M - CH2Br].
=
=
=
1-Bromo-3-butyn-2-one, 2. 1H NMR: d 4.05 (s, 2H), 3.41 (s, 1H); 13C
NMR: d177.6, 82.2, 79.1, 35.2: IR (net NaCl plates) nmax, cmꢂ1: 3290, 2250, 2100,
1680; HRMS: observed for C4H3BrO: 147.9340; calcd: 147.9347.
1
1,3-Dibromo-3-buten-2-one, 3. H NMR d 6.92 (d, 1H), j 5.95 (dd, 1H, J ¼ 2–
7 Hz), 6.45(d. 1H, J ¼ 2.7 Hz, 4.33 (s, 2H.); 13C NMR d 186.1, 131.0, 127.1. 30.1 32.6,
131.1, 133.2, 191.5;;GC= MS (EI 70eV) m=z (relative abundance) [Assignment]: 230
(15), 228 (28), 226 (14), 135 (100), 133, 107, (41), 105, 95, 93, 81(12) 79.
FUNDING
We thank the Research Council of Norway for financial support via the
KOSK-II program.
REFERENCES
1. Westerlund, A.; Gras, J.-L.; Carlson, R. Investigation of 1-bromo-3-buten-2-one as building
block in organic synthesis. Tetrahedron 2001, 57, 5879–5883.
2. Herman, T.; Carlson, R. Nouvelle voie d’acces au squelette cyclopentenoidique. Tetra-
hedron Lett. 1989, 30, 3657–3658.
3. Westerlund, A.; Carlson, R. Synthesis of 1-bromo-3-buten-2-one. Synth. Commun. 2002,
29, 4035–4042.
4. Carlson, R.; Descomps, A.; Mekonnen, A.; Westerlund, A.; Havelkova, M. Improved
synthesis of 1-bromo-3-buten-2-one. Synth. Commun. 2011, 41, 2039–2945.
5. Mekonnen, A.; Westerlund, A.; Havelkova, M.; Descomps, A.; Carlson, R. Synthesis of 1-
bromo-3-butyn-2-one and 1,3-dibromo-3-buten-2-one. Synth. Commun. 2009, 39, 2472–2480.
6. Kim, K. S.; Song, Y. H.; Lee, B. H.; Hahn, C. S. Efficient and selective cleavage of acetals
and ketals using ferric chloride adsorbed on silica gel. J. Org. Chem. 1986, 51, 404–407.
7. Fadel, A.; Yefasah, R.; Salaun, J. Anhydrous iron (III) chloride dispersed on silica gel; III.
A convenient and mild reagent for deacetalization in dry medium. Synthesis 1987, 37–40.