LETTER
1117
A Modified Low-cost Preparation of Chloromethyl Methyl Ether (MOM-Cl)
A
M
odifie
d
Low-cost
i
Prepara
c
tion of Chl
h
oromethyl
M
a
ethyl Etherel Reggelin,* Sebastian Doerr
Institut für Organische Chemie, Technische Universität Darmstadt, Petersenstr. 22, 64287 Darmstadt, Germany
Fax +49-6151-16-5531; E-mail: re@punk.oc.chemie.tu-darmstadt.de
Received 10 February 2004
O
Abstract: The versatile reagent chloromethyl methyl ether (MOM-
cat. H2SO4
60 °C
Cl) is synthesized by using inexpensive starting materials in a large
scale. A modification of the existing methods reduces material costs
by more than 80%.
O
O
+
Cl
Key words: protecting group, MOM-Cl, alcohols, phenols, acetals
1
2
O
Chloromethyl methyl ether (MOM-Cl, 4) is an important
reagent in organic synthesis. It is the primary reagent for
the conversion of alcohols to methoxy methyl (MOM)
ethers, being an important protecting group.1 Due to the
fact that commercially available MOM-Cl contains the
highly carcinogenic bis(chloromethyl)ether, several
preparations were developed which do not produce the
toxic by-product.2
+
Cl
O
O
3
4
MOM-Cl
Scheme 1
In this paper, we describe a modified procedure in which
the very inexpensive reagents benzoyl chloride (1) and
dimethoxymethane (2) are used as starting materials
(Scheme 1). The product, which is collected by distilla-
tion from the reaction mixture, is almost completely free
of bis(chloromethyl)ether. Due to the use of cheap starting
materials, one mole of MOM-Cl (4) can be synthesized at
a cost of about US $ 6.20.3
as a colorless liquid (bp 55–57 °C). The purity, especially
the absence of the bis(chloromethyl)ether can be validated
by 1H NMR spectroscopy and gas chromatography.7
Acknowledgment
The authors would like to thank the Fonds der Chemischen Indu-
strie for the financial support by a Kekulé fellowship (S. D.).
In summary the new preparation saves more than 80% of
the chemical costs compared to the published procedures2
and 97% compared to buying MOM-Cl (4).3
References
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed; John Wiley and Sons: Weinheim, 1999.
(2) (a) Amato, J. S.; Karady, M.; Sletzinger, M.; Weinstock, L.
M. J. Org. Chem. 1994, 59, 6499. (b) Linderman, R. J.;
Jaber, M.; Griedel, B. D. J. Org. Chem. 1994, 59, 6499.
(c) Chong, J. M.; Shen, L. Synth. Commun. 1998, 28, 2801.
(3) Material costs are calculated from the prices quoted in the
Aldrich Chemical Co. catalog (2003). For comparison, one
mole of chloromethyl methyl ether costs 229 US $. A
commercial sample of chloromethyl methyl ether contained
about 4% of bis(chloromethyl)ether.
(4) To ensure gas tightness, PTFE-sleeves were used on all glass
connections.
(5) All reagents were purchased by common suppliers and used
as received without any further purification.
(6) The integrals of the product signals (d = 3.52 and 5.46 ppm)
are compared with those of dimethoxymethane (d = 3.34 and
4.56 ppm).
(7) Without further purification, the product contains about 1%
dimethoxymethane (1H NMR, d = 3.34 and 4.56 ppm). This
is sufficient for most applications. The content of
bis(chloromethyl)ether was found to be less than 0.1% (GC,
conditions 50 m × 0.32 mm FS-SE-52-CB-0.25 fused silica
column, column temperature 60 °C, injector temperature
240 °C, detector temperature (FID), nitrogen flow 1 mL/min
tR (MOM-Cl) = 5.79 min, tR [bis(chloromethyl)ether] = 7.97
min.
Due to the acute toxicity and carcinogenicity of chloro-
methyl methyl ether (MOM-Cl), the reaction must be
performed in a well-ventilated hood. A 1000 mL, two-
necked, round-bottomed flask is equipped with a magnet-
ic stirring bar and a reflux condenser.4 The flask is
charged with 140.6 g (1.0 mol, 1 equiv) benzoyl chloride
(1), 76.1 g (1.0 mol, 1 equiv) dimethoxymethane (2) and
5.0 g (51.0 mmol) concentrated sulfuric acid.5 A balloon
filled with Ar is connected to the condenser and the flask
is flushed with Ar briefly and then sealed by a glass stop-
per. The mixture is stirred and heated in an oil bath which
is thermostated at 60–65 °C. Conversion can be checked
1
by H NMR-spectroscopy.6 After 64 hours the reaction
mixture is allowed to cool to room temperature. The
reflux condenser is replaced by a distillation bridge
equipped with a thermometer and a balloon filled with Ar.
After flushing with Ar again, the solution is heated step-
wise up to 130 °C to collect 59.4 g (74%) of the product 4
SYNLETT 2004, No. 6, pp 1117–1117
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6.
0
5.
2
0
0
4
Advanced online publication: 25.03.2004
DOI: 10.1055/s-2004-820049; Art ID: G04204ST
© Georg Thieme Verlag Stuttgart · New York