Bromoacetyl bromide: A versatile and selective cleaving agent for ethers and acetals

Article abstract of DOI:10.1081/SCC-120002510

It is shown that bromoacetyl bromide can be utilized for the selective cleavage of ethers and acetals in high yields. With cyclic ethers and acetals as starting materials, cleavage products are produced with two strategically positioned bromo substituents which may be exploited for selective extention of the carbon chain.

Full text of DOI:10.1081/SCC-120002510

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BROMOACETYL BROMIDE: A VERSATILE AND
SELECTIVE CLEAVING AGENT FOR ETHERS AND
ACETALS
David F. Schneider a & Murray S. Viljoen a
a Chemistry Department , University of Stellenbosch , Stellenbosch, 7602, South Africa
Published online: 16 Aug 2006.
To cite this article: David F. Schneider & Murray S. Viljoen (2002) BROMOACETYL BROMIDE: A VERSATILE AND
SELECTIVE CLEAVING AGENT FOR ETHERS AND ACETALS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:5, 721-728, DOI: 10.1081/SCC-120002510
To link to this article: http://dx.doi.org/10.1081/SCC-120002510
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SYNTHETIC COMMUNICATIONS, 32(5), 721–728 (2002)
BROMOACETYL BROMIDE:
A VERSATILE AND SELECTIVE
CLEAVING AGENT FOR
ETHERS AND ACETALS
David F. Schneider* and Murray S. Viljoen
Chemistry Department, University of Stellenbosch,
Stellenbosch 7602, South Africa
ABSTRACT
It is shown that bromoacetyl bromide can be utilized for the
selective cleavage of ethers andacetals in high yields. With
cyclic ethers andacetals as starting materials, cleavage
products are produced with two strategically positioned
bromo substituents which may be exploitedfor selective
extention of the carbon chain.
During a recent investigation in our laboratory that centredaround
the synthesis of annulated 4-alkylidenebutenolides from natural occurring
diosphenols,1 4-bromobutyl bromoacetate (1) was formedas the major
reaction product when the bromoacetylation of diosphenol was conducted
with bromoacetyl bromide in THF under normal reaction conditions.
In fact, treatment of bromoacetyl bromide with an excess of THF indeed
produced the dibromoester (1) in a near quantitative yield.
*Corresponding author.
721
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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SCHNEIDER AND VILJOEN
This observation prompted us to undertake a detailed study of the
ether cleaving properties of bromoacetyl bromide. By utilizing cyclic
ethers andrelatedcompounds, e.g., cyclic acetals, as substrates the reaction
products would be endowed with two markedly different halogen substi-
tutedelectrophilic centres for further selective synthetic elaboration.
It is well documentedthat THF can be cleavedby ordinary acyl
halides to produce the corresponding mono-haloesters2,3 in reasonable to
high yields. These transformations are generally catalyzed by zinc metal,4
sodium iodide,5 samarium triiodide,6 magnesium iodide7 andtitanium(II),
8,9
tin(II), cobalt(II) andzinc chlorides.
The cleavage of 1,4-dioxane and 3,4-dihydro-2H-pyran was next
attempted, but treatment of the former with bromoacetyl bromide
(105ꢀC/9 h) only yielded unreacted starting material, while an intractable
black tar was produced when a mixture of 3,4-dihydro-2H-pyran and bromo-
acetyl bromide was stirred at room temperature. On the other hand,
treatment of the cyclic acetal (2) with bromoacetyl bromide gave a high

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BROMOACETYL BROMIDE
723
yieldof the dibromoester ( 3). A similar result was obtainedwhen an excess of
bromoacetyl bromide was used, and the total absence of the dibromoesters
(4) and( 5) demonstrated the selectivity of the cleavage process. The dibromo-
ester (3) was previously synthesizedfrom bromoacetyl bromied and
ethylenebromohydrin in an unspecified yield.10 In the latter synthesis, how-
ever, the nucleophilic bromide ion was wasted as an unutilized byproduct.
Treatment of the tetrahydropyranyl ether (6) with a slight excess
(10 mol%) of bromoacetyl bromide resulted in selective formation of ethyl
bromoacetate (7) and2-bromotetrahydropyran ( 8).11 The lower isolated
yieldof ( 8) as comparedto ( 7) can be ascribedto the relative instability
of the former which normally precludes its isolation.12
In order to extend the versatility of bromoacetyl bromide as a gene-
rally applicable ether cleavage reagent, the fission of aliphatic andaromatic
acyclic ethers andacetals was next investigated. Dimethoxymethane ( 9)
underwent facile cleavage upon treatment with a two-fold excess of bromo-
acetyl bromide under mild conditions, to afford methyl bromoacetate (10)
andthe volatile bromoether ( 11) as the reaction products. Attempted clea-
vage of 2,2-dimethoxypropane with bromoacetyl bromide led to complete
decomposition of the reaction mixture, but 1,2-dimethoxyethane (12)
reactedsmoothly to give high yields of ( 13) and( 14) selectively, depending
on the reaction conditions employed. The bromoacetates (13) and (14) are
13
generally usedas antifouling agents, e.g., (13) is specifically usedfor the

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SCHNEIDER AND VILJOEN
13
protection of metals against the action of algae andbacteria in sea water.
Dibromodiacetate (14) has foundapplication as an inhibitor of fermenta-
tion in apple juice concentrates,14 as an agent for the prevention of deposits
in motor oils,15 as a potent germicide and as a highly effective retarding
agent of initial foliation in plants.16
Cleavage of diethylene glycol dimethyl ether (15) with bromoacetyl
bromide also proceeded smoothly to afford the bromoacetate (16) selec-
tively. The dibromodiacetate (17), which foundgeneral application as a
fungicide in the wood pulp industry,17 was formedin high yieldwhen the
bromoester (16) was treatedwith a slight excess of bromoacetyl bromide
under slightly more drastic reaction conditions.
Dibenzyl ether (18) was efficiently cleavedby treatment with bromo-
acetyl bromide, but methoxybenzene (21) was inert under comparable reac-
tion conditions. The latter ether (21) could, however, be cleaved in moderate
yield when zinc chloride (12.5 mol%) was added as catalyst. In agreement
with these results it was foundthat 1-methoxy-2-phenoxyethane ( 23) could
be cleavedchemoselectively to produce the bromoester ( 24) in goodyield.
The inertness of the phenyl–oxygen bondtowardcleavage with bromoacetyl
bromide was once again demonstrated by the lack of reaction when the
bromoester (24) was treatedwith bromoacetyl bromide.
EXPERIMENTAL
All operations were carriedout in an argon atmosphere. NMR spectra
were recorded in deuteriochloroform on a Varian VXR 300 instrument,

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725
while mass spectra were taken on a Varian MAT 311 A spectrometer.
COSY, HETCOR andDEPT experiments were performedto interpret
more complex NMR spectra. Yields refer to isolated compounds, the
purity andstructures of which were accurately establishedby NMR and
mass spectral techniques. The spectral andother physical data of reaction
products are cited below only in those cases where useful data could not be
foundin the chemical literature.
Cleavage of Ethers and Acetals by Bromoacetyl Bromide
Generalprocedure: Freshly distilled bromoacetyl bromide was added
dropwise to the ether or acetal andstirring of the reaction mixture was
maintainedat the specifiedtemperatures (see table for specific reaction
conditions). The generally simple reaction mixtures were fractionally dis-
tilledby implementing a specially designedfan oven equippedwith a con-
cealedheating element anda contact thermometer for accurate temperature
control, to give the following pure reaction products.
Entry 1: 4-Bromobutyl bromoacetate (1) (7.18 g, 99%), b.p. 65ꢀC
(air-bath temp.)/0.04 mmHg; dH 1.76–2.07 (m, 4H), 3.37–3.53 (m, 2H),
3.84 (s, 2H), 4.14–4.29 (m, 2H); dC 25.79 (t, CH2), 27.12 (t, CH2), 29.08
(t, CH2), 32.94 (t, CH2), 65.25 (t, CH2), 167.19 (s, >C¼O); MþꢁBr,
192.9867 andM þꢁC2H4Br, 164.9550. Calcdfor C H10O2Br79: M, 192.9864
6
andfor C H6O2Br79: M, 164.9551.
4
Entry 2: 2-Bromoethyl bromoacetate (3) (5.60 g, 89%), b.p. 100ꢀC
(air-bath temp.)/7 mmHg (lit.10 118ꢀC/16 mmHg); dH 3.53 (t, J 6.1 Hz,
2H), 3.88 (s, 2H), 4.48 (t, J 5.9 Hz, 2H); dC 28.62 (t, CH2), 35.97 (t, CH2),
63.79 (t, CH2), 167.23 (s, >C¼O); Mþ, 244, 245.8715 and248. Calcdfor
C4H6O2Br2: M, 244, 245.8715 and248.
Entry 3: A mixture of ethyl bromoacetate (7) (4.40 g, 86%), b.p. 62ꢀC
(air-bath temp.)/15 mmHg (lit.18 158–162ꢀC) and 2-bromotetrahydropyran
(8) (2.80 g, 55%), b.p. 62ꢀC (air-bath temp.)/15 mmHg, (lit.11 61–63ꢀC/
26 mmHg); dH 1.70–1.80 (m, 3H), 2.10–2.12 (m, 3H), 3.81–3.89 (m, 1H),
3.94–4.03 (m, 1H), 6.77–6.80 (m, 1H).
Entry 5: 2-Methoxyethyl bromoacetate (13) (3.33 g, 95%), b.p. 50ꢀC
(air-bath temp.)/0.2 mmHg; dH 3.39 (s, 3H), 3.62 (t, J 4.7 Hz, 2H), 3.89
(s, 2H), 4.33 (t, J 4.7 Hz, 2H); dC 25.79 (t, CH2), 58.98 (q, CH3), 65.16
(t, CH2), 70.08 (t, CH2), 167.26 (s, >C¼O); MþꢁC3H6O, 137.9343 and
139.9332. Calcdfor C H9O3Br-C3H6O: 137.9316 and139.9297.
5
Entry 6: 1,2-bis(Bromoacetoxy)ethane (14) (0.74 g, 88%), b.p. 140ꢀC
(air-bath temp.)/2 mmHg (lit.16 135–6ꢀC/1.5 mm); dH 3.88 (s, 4H), 4.42

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SCHNEIDER AND VILJOEN
Table. The Cleavage of Ethers andAcetals with Bromoacetyl Bromide
(s, 4H); dC 25.75 (t, CH2), 65.10 (t, CH2), 167.19 (s, >C¼O); Mþꢁ
C2H2O2Br, 167 and165. Calcdfor C 6H8O4Br2-C2H2O2Br: 167 and165.
Entry 7: 2-(2-Methoxyethoxy)ethyl bromoacetate (16) (6.09 g, 85.0%),
b.p. 100ꢀC (air-bath temp.)/1 mmHg; dH 3.39 (s, 3H), 3.56 (m, 2H), 3.66
(m, 2H), 3.74 (m, 2H), 3.88 (s, 2H), 4.34 (m, 2H); dC 25.80 (t, CH2Br), 59.08

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727
(q, CH3), 65.30 (t, CH2), 68.81 (t, CH2), 70.58 (t, CH2), 71.89 (t, CH2),
167.23 (s, >C¼O); MþꢁC3H7O2, 167 and165. Calcdfor C 7H13O4Br-
C3H7O2: M, 167 and165.
Entry 8: bis(2-Bromoacetoxyethyl )ether (17) (3.60 g, 83%), b.p. 160ꢀC
(air-bath temp.)/0.03 mmHg; dH 3.74 (t, J 4.7 Hz, 4H), 3.88 (s, 4H), 4.34
(t, J 4.7 Hz, 4H); dC 25.75 (t, CH2), 65.10 (t, CH2), 68.76 (t, CH2), 167.19 (s,
>C ¼O); MþꢁC4H6O3Br, 167 and165. Calcdfor C 8H12O5Br2-C4H6O3Br:
M, 167 and165.
Entry 10: 2-Phenoxyethyl bromoacetate (24) (5.37, 80%), b.p. 90–5ꢀC
(air-bath temp.)/0.03 mmHg; dH 3.85 (s, 2H), 4.10–4.22 (m, 2H), 4.43–4.57
(m, 2H), 6.93–7.32 (m, arom. H, 5H); dC 25.60 (t, CH2Br), 64.50 (t, CH2),
65.51 (t, CH2), 114.67 (d, 2 ꢂ o-arom. C), 121.35 (d, p-arom. C), 129.56
(d, 2 ꢂ m-arom. C), 158.34 (s, arom. C), 167.20 (s, >C¼O); Mþ, 257.9844
and259.9865. Calcdfor C 10H11O3Br: M, 257.9892 and259.9872.
Cleavage of Methoxybenzene (21) with Bromoacetyl Bromide
in the Presence of Zinc Chloride as Catalyst
Freshly distilled bromoacetyl bromide (18.56 g, 91.94 mmol) was
added dropwise to stirred suspension of zinc chloride (1.57 g, 11.5 mmol)
in methoxybenzene (10.0 g, 95.59 mmol) during 15 min at 50ꢀC. The result-
ꢀ
ing reaction mixture was stirredfor 1 h at 50 C and an additional 2.5 h at
70ꢀC, diluted with benzene (50 cm3), whereafter celite was added and the
suspension filtered. The residue from the filtrate was dispersed in benzene
(50 cm3), thoroughly stirred under reflux, filtered and fractionally distilled
at 120ꢀC/5.0 mmHg to remove a mixture of unreactedbromoacetyl
bromide (3.15 g, 17.0%) and methoxybenzene (0.93 g, 9.3%). Separation
of the distillation residue on a chromatotron [4 mm silica gel plate,
activatedat 120 ꢀ/5 h, ether–petroleum ether (1 : 4) as mobile phase] and
fractional distillation of the residue from the eluate yielded phenyl bromo-
acetate (22) (7.41 g, 38%), b.p. 80ꢀC (air-bath temp.)/0.11 mmHg (lit.20
140ꢀC/20 mmHg).
ACKNOWLEDGMENTS
We thank Mr. H. S. C. Spies for the NMR spectra andmany valuable
discussions and Ms. V. Truter for the mass spectra. Financial support by
the University of Stellenbosch andtechnical assistance by Mr. M. C.
de Jongh and his staff is gratefully appreciated.

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SCHNEIDER AND VILJOEN
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Receivedin the UK December 13, 2000

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