Organic Syntheses, CV 6, 12
Submitted by G. R. Newkome
1 and D. L. Fishel
2.
Checked by G. Swift and W. D. Emmons.
1. Procedure
Caution! Hydrazines are toxic and should be handled in a
hood. Anhydrous
hydrazine is extremely reactive with oxidizing agents (including air) and should always be used behind a protective screen.
A.
Acetophenone N,N-dimethylhydrazone. A mixture of
acetophenone (12.0 g., 0.100 mole), anhydrous
N,N-dimethylhydrazine (18.0 g., 0.300 mole) (Note
1),
absolute ethanol (25 ml.), and
glacial acetic acid (1 ml.) (Note
2) is heated at reflux for 24 hours. During this period the colorless solution becomes bright yellow. The volatile reactants and solvent are removed under reduced pressure and the residual oil is fractionally distilled through a
10-cm. Vigreux column, giving a small forerun of unreacted
acetophenone, b.p.
30–40° (0.15 mm.), followed by
14.6–15.2 g. (
90–94%) of
acetophenone N,N-dimethylhydrazone, b.p.
55–56° (0.15 mm.),
nD25 1.5443 (Note
3) and (Note
4).
B.
Acetophenone hydrazone. A mixture of
acetophenone N,N-dimethylhydrazone (8.1 g., 0.050 mole) and anhydrous
hydrazine (6.4 g., 0.20 mole) (Note
5) in
absolute ethanol (15 ml.) is heated at reflux until the reaction mixture turns colorless (Note
6). The volatile materials are removed on a
rotary evaporator without allowing the flask temperature to rise above 20° (Note
7). The colorless residual
acetophenone hydrazone, which solidifies as the last traces of solvent are removed, weighs
6.5–6.6 g. (
97–99%) and is sufficiently pure for most purposes, m.p.
24–25° (Note
8) and (Note
9).
2. Notes
2. It is not necessary to use glacial
acetic acid as a catalyst, but without it the reaction time required for completion is prolonged.
3. Physical constants previously reported:
3 b.p.
100.5–102° (10 mm.),
nD25 1.5455.
4. This method has been used to prepare various
N,N-dimethylhydrazones in 70–99% yield.
4
5. A good
commercial grade of anhydrous hydrazine (Eastman Organic Chemicals) is satisfactory.
6. The reaction time for complete conversion is usually less than 24 hours. A convenient "end point" is the visual color change from bright yellow to colorless or very pale yellow.
7. It is of utmost importance that the flask temperature during the removal of the volatile materials be kept below 20° to minimize possible azine formation by decomposition of the hydrazone.
8. The reported melting points are 16–20°,
5 22°,
6 24–25°,
4,7 and 26°.
7
3. Discussion
This synthetic process is applicable to the preparation of most hydrazones from aldehydes and ketones. The two-step preparation offers several distinct advantages over the one-step method:
6,9 (1) The yield of both steps is high; (2) the product is not contaminated with azine; (3) the isolated product is pure enough to be used in subsequent reactions without further purification. This method excels in the preparation of unstable liquid or low-melting hydrazones over the common methods of preparation.
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved