Org. Synth. 1973, 53, 35
Submitted by John N. Bridson and John Hooz1
Checked by Dennis R. Murayama and Ronald Breslow.
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).
was prepared by the method in Org. Synth:
, Coll. Vol. 5
, 351 (1973), using 10% extra 2-(2-ethoxyethoxy)ethanol
and an extra 100 ml. of water over that recommended, to prevent stirring difficulties in the later stages of the distillation. The ethereal diazomethane
solution was dried at 0° over potassium hydroxide
pellets, and the concentration was determined by reaction of an aliquot with benzoic acid
and analyzing the resulting methyl benzoate
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.)
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.
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.
The submitters obtained a similar yield on twice the scale reported here.
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
evolve the theoretical amount of nitrogen
on titration with 3 N hydrochloric acid
Apart from the reaction of diazomethane
with benzoyl chloride
has been prepared by the reaction of 2-aminoacetophenone hydrochloride
with sodium nitrite
from the mixed anhydride of benzoic acid
and ethyl carbonate
from benzoyl chloride
and potassium methyldiazotate
by treating the enamine formed from 2-formylacetophenone
with p-toluenesulfonyl azide
and from the reaction of the sodium enolate of 2-formylacetophenone
with p-toluenesulfonyl azide
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
(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 C6
(96%), and (CH3
(96%). However, this low temperature procedure is inapplicable to substrates with especially acidic α-hydrogens, such as phenylacetyl chloride
, presumably due to competing ketene
This preparation is referenced from:
Chemical Abstracts Nomenclature (Collective Index Number);
sodium enolate of 2-formylacetophenone
calcium chloride (10043-52-4)
hydrochloric acid (7647-01-0)
diethyl ether (60-29-7)
sodium hydrogen carbonate (144-55-8)
sodium nitrite (7632-00-0)
Benzoic acid (65-85-0)
benzoyl chloride (98-88-4)
potassium hydroxide (1310-58-3)
methyl benzoate (93-58-3)
Triethylamine hydrochloride (554-68-7)
phenylacetyl chloride (103-80-0)
calcium hydride (7789-78-8)
Ethanone, 2-diazo-1-phenyl- (3282-32-4)
2-aminoacetophenone hydrochloride (5468-37-1)
p-toluenesulfonyl azide (941-55-9)
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