Organic Syntheses, CV 6, 386
Submitted by John N. Bridson and John Hooz
1.
Checked by Dennis R. Murayama and Ronald Breslow.
1. Procedure
A solution of
0.375 mole of diazomethane in
1 l. of diethyl ether (Note
1) is placed in a
2-l. flask fitted with a large
magnetic stirring bar, a
two-necked adapter, equipped with a
drying tube (containing potassium hydroxide pellets), and a
pressure-equalizing dropping funnel.
Triethylamine (37.9 g., 52.1 ml., 0.375 mole) (Note
2) is added, and the flask contents are cooled to
ca. −10° to −5°. A solution of
52.75 g. (43.56 ml., 0.3754 mole) of benzoyl chloride (Note
3) in
300 ml. of dry ether is added to the stirred mixture over a period of 0.5 hour (Note
4). An additional
50 ml. of ether is rinsed through the dropping funnel. Stirring is continued for one hour at approximately 0°, then overnight at room temperature.
The resulting
triethylamine hydrochloride precipitate (
41.4 g.,
81%) is filtered and washed with
100 ml. of dry ether. The solvent is removed from the combined filtrate by rotary evaporation, and the semi-solid residue crystallizes to an orange-red solid after refrigeration for several hours at
ca. 5°. Crystallization from a mixture of
150 ml. of pentane and
120 ml. of dry ether affords
38.8 g. of
diazoacetophenone as yellow square plates, m.p.
44–48°. Concentration of the mother liquor and extraction of the residue with boiling
pentane yields an additional
7.8 g. of pale yellow rods, m.p.
47.5–48.5°, bringing the total yield to
46.6 g. (
85%) (Note
5) and (Note
6).
2. Notes
2.
Triethylamine, purchased from J. T. Baker Chemical Company, was refluxed over
calcium hydride, then fractionally distilled through a
40-cm. Vigreux column, b.p.
81–82° (700 mm.); b.p.
89.5–90° (760 mm.).
3.
Benzoyl chloride, obtained from British Drug House (Canada) Ltd., was purified, as described in
Org. Synth.,
Coll. Vol. 3, 112 (1955), by washing a
benzene solution with 5% aqueous
sodium hydrogen carbonate, drying over
calcium chloride, and fractional distillation through a 40-cm. Vigreux column, b.p.
69–71° (12 mm.). The checkers used a fresh bottle, from Matheson, Coleman and Bell, without purification.
4. In the later stages of the addition a cake of crystals forms, preventing adequate stirring. This difficulty is overcome by temporarily interrupting the addition and swirling the flask manually—stirring then continues normally.
5. The submitters obtained a similar yield on twice the scale reported here.
6. Although crystallization from
pentane gives better crystals, with an improved melting point range, recrystallization of the whole batch would require approximately 3 l. of solvent. Samples obtained from both
ether-
pentane and
pentane evolve the theoretical amount of
nitrogen on titration with 3
N hydrochloric acid.
3. Discussion
The reaction of an acid chloride with
diazomethane illustrates a general method of preparing diazoketones. The acid chloride is slowly added to at least two equivalents of
diazomethane; the
hydrogen chloride liberated (Eq. 1) is then consumed according to Eq. 2. When the order of addition is reversed (
e.g., acid chloride is in excess) and only
1 mole of diazomethane is employed, the diazoketone reacts with
hydrogen chloride, forming the α-chloroketone (Eq. 3).
The method described here, discovered independently by Newman and Beal,
3 and Berenbom and Fones,
4 employs
triethylamine (1 equivalent) to react with the
hydrogen chloride; thus, only one equivalent of
diazomethane is necessary. This modification was originally restricted to the use of either aromatic- or aliphatic acid chlorides lacking α-hydrogen atoms. Acid chlorides bearing α-hydrogens produce a mixture of products, presumably due to competing ketene formation and subsequent side reactions.
More recently it has been shown that, by operating at lower temperatures (−78°C), even simple aliphatic acid chlorides may also be successfully employed.
10 Some examples are the preparation of C
6H
5CH
2CH
2COCHN
2 (96%),
cyclo-C
6H
11COCHN
2 (96%), CH
3(CH
2)
7COCHN
2 (96%), and (CH
3)
2CHCOCHN
2 (96%). However, this low temperature procedure is inapplicable to substrates with especially acidic α-hydrogens, such as
phenylacetyl chloride, presumably due to competing
ketene formation.
This preparation is referenced from:
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