Organic Syntheses, CV 5, 825
Checked by John H. Sellstedt, Wayland E. Noland, and William E. Parham.
1. Procedure
The hot mixture is filtered with suction into a
1-l. round-bottomed flask through a
Büchner-type sintered glass funnel provided with a ground joint (Note
1). The solid on the funnel is washed successively with two
50-ml. portions of hot carbon tetrachloride. The solvent is removed from the filtrate under reduced pressure on a
water bath (Note
2). The flask is then fitted with a
reflux condenser, and
400 ml. of commercial absolute ethanol and
65 ml. (0.81 mole) of good grade pyridine (Note
3) are added to the residue.
The solution is heated at the reflux temperature for 45 minutes and immediately transferred to a
wide-mouthed Erlenmeyer flask. Crystallization begins at once, and, after the mixture is cooled, the crystals of nearly pure
o-nitrobenzylpyridinium bromide are collected, washed with cold
ethanol, and used in the next step (Note
4).
B.
N-(p-Dimethylaminophenyl)-α-(o-nitrophenyl)nitrone. The wet
o-nitrobenzylpyridinium bromide, together with
100 g. (0.536 mole) of p-nitrosodimethylaniline hydrochloride (Note
5) and
800 ml. of ethanol are introduced into a
2-l. three-necked flask equipped with an
efficient stirrer,
thermometer, and a
dropping funnel, and immersed in an
ice-salt bath. The stirrer is started, and a solution of
54 g. (1.35 mole) of sodium hydroxide in 500 ml. of water is added at 0–5° (Note
6). The color changes gradually from yellow to green, brown, and orange. The stirring is continued at 5–10° over a period of 1 hour. At the end of this time 500 ml. of ice-cold water is added to the flask, and the orange
N-(p-dimethylaminophenyl)-α-(o-nitrophenyl)nitrone is collected on a
large Büchner funnel, pressed well, and washed with cold water. The
nitrone is used in the next step without further purification (Note
7).
The light brown material is best purified by distillation under reduced pressure. The yellow aldehyde is collected at
120–140° (3 mm.) (Note
10) and melts at
41–44°. This material weighs
48–54 g. (
47–53% overall yield based on
N-bromosuccinimide) and is sufficiently pure for most uses (Note
11), (Note
12).
2. Notes
1. Suction filtration is necessary. The filtration is conveniently carried out through a regular
Büchner funnel connected through a
rubber stopper to a
1-l. suction flask.
Since o-nitrobenzyl bromide is a powerful lachrymator, the filtration should be carried out in a fume hood.
2. The checkers used a
rotary evaporator.
3. The checkers used
Merck Reagent A.C.S. grade pyridine.
6. Sometimes a difficulty in stirring is encountered, and
100–200 ml. of ethanol should be added to the reaction mixture. The checkers found that the reaction mixture became a very thick paste which was quite difficult to stir. Use of a sturdy
Hershberg stirrer is recommended.
7. The wet material contains about 55–65% of water. When the product is dried in a
vacuum desiccator and recrystallized from
ethyl acetate or
acetone, it melts at
130–134°.
8. The solution is prepared by careful addition of
170 ml. of concentrated sulfuric acid to 850 ml. of water.
10. The checkers collected the product at
97–99° (1 mm.).
11. Very pure material can be obtained by dissolving
o-nitrobenzaldehyde in
toluene and precipitating with
petroleum ether, according to earlier instructions.
3
12. The same yields are obtained when the scale of this preparation is doubled.
3. Discussion
4. Merits of the Preparation
The present procedure is a general method for preparing aromatic and heterocyclic aldehydes. It is of particular value in the synthesis of o-nitrobenzaldehydes in 100–200 g. lots. The benzaldehydes are useful starting materials for cinnamic acids, β-nitrostyrenes, etc. The manipulations are simple, the yields are reproducible, and the intermediates can be easily isolated and purified. The intermediates themselves have many synthetic uses.
The submitter has prepared the
fluoro-o-nitrobenzaldehydes shown in Table I by application of this method.
6
TABLE I
FLUORO-o-NITROBENZALDEHYDES
|
Position of Fluorine |
M. P. of Fluoro-2-nitrobenzylpyridinium Bromide, °C |
M. P. of N-(p-dimethylaminophenyl)- α-(fluoro-o-nitrophenyl)nitrone, °C |
M. P. of Aldehyde, °C |
Overall Yield, % |
|
4 |
200–201 |
164–165 |
32–33 |
55–62 |
5 |
189–190 |
155–156 |
93–95 |
45–55 |
6 |
202–204 |
151–152 |
62–63 |
59–66 |
|
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