Organic Syntheses, CV 6, 644
Submitted by J. C. Collins
1 and W. W. Hess
2.
Checked by R. T. Uyeda and R. E. Benson.
1. Procedure
Caution! The reaction of
chromium trioxide with
pyridine is extremely exothermic; the preparation should be conducted in a
hood, observing the precautions noted.
A.
Dipyridine chromium(VI) oxide (Note
1). A dry,
1-l., three-necked flask fitted with a sealed
mechanical stirrer, a
thermometer, and a
drying tube, is charged with
500 ml. of anhydrous pyridine (Note
2), which is stirred and cooled to approximately 15° (Note
3) with an
ice bath. The drying tube is periodically removed and
68 g. (0.68 mole) of anhydrous chromium(VI) oxide (Note
4) is added in portions through the neck of the flask over a 30-minute period. The
chromium trioxide should be added at such a rate that the temperature does not exceed 20° and in such a manner that the oxide mixes rapidly with the
pyridine and does not adhere to the side of the flask (Note
5). As the
chromium trioxide is added, an intensely yellow, flocculent precipitate separates from the
pyridine and the viscosity of the mixture increases. When the addition is complete, the mixture is allowed to warm slowly to room temperature with stirring. Within one hour the viscosity of the mixture decreases and the initially yellow product changes to a deep red, macrocrystalline form that settles to the bottom of the flask when stirring is discontinued. The supernatant
pyridine is decanted from the complex and the crystals are washed several times by decantation with
250-ml. portions of anhydrous petroleum ether. The product is collected by filtration on a sintered
glass funnel and washed with anhydrous
petroleum ether, avoiding contact with the atmosphere as much as possible. The complex is dried at 10 mm. until it is free-flowing, leaving
150–160 g. (
85–91%) of
dipyridine chromium(VI) oxide3 as red crystals. The product is extremely hygroscopic; contact with moisture converts it rapidly to the yellow
dipyridinium dichromate.
4 It is stored at 0° in a brown bottle (Note
6).
B.
General oxidation procedure for alcohols. A sufficient quantity of a
5% solution of dipyridine chromium(VI) oxide (Note
1) in anhydrous
dichloromethane (Note
7) is prepared to provide a sixfold molar ratio of complex to alcohol, an excess usually required for complete oxidation to the aldehyde. The freshly prepared, pure complex dissolves completely in
dichloromethane at 25° at 5% concentration, giving a deep red solution, but solutions usually contain small amounts of brown, insoluble material when prepared from crude complex (Note
8). The alcohol, either pure or as a solution in anhydrous
dichloromethane, is added to the red solution in one portion with stirring at room temperature or lower. The oxidation of unhindered primary (and secondary) alcohols proceeds to completion within 5 to 15 minutes at 25° with deposition of brownish-black, polymeric, reduced
chromium–
pyridine products (Note
9). When deposition of reduced chromium compounds is complete (monitoring the reaction by GC or TLC is helpful), the supernatant liquid is decanted from the (usually tarry) precipitate, which is rinsed thoroughly with
dichloromethane (Note
10).
C.
Heptanal. A dry,
1-l. three-necked round-bottomed flask is equipped with a
mechanical stirrer, and
650 ml. of anhydrous dichloromethane (Note
7) is added. Stirring is begun and
77.5 g. (0.300 mole) of dipyridine chromium(VI) oxide (Note
1) is added at room temperature, followed by
5.8 g. (0.050 mole) of 1-heptanol (Note
11) in one portion. After stirring for 20 minutes, the supernatant solution is decanted from the insoluble brown gum, which is washed with three
100-ml. portions of ether. The
ether and
dichloromethane solutions are combined and washed successively with
300 ml. of aqueous 5% sodium hydroxide,
100 ml. of 5% hydrochloric acid (Note
12), two
100-ml. portions of saturated aqueous sodium hydrogen carbonate, and, finally, with
100 ml. of saturated aqueous sodium chloride. The organic layer is dried over anhydrous
magnesium sulfate, and the solvent is removed by distillation. Distillation of the residual oil at reduced pressure through a small Claisen head separates
4.0–4.8 g. (
70–84%) of
heptanal, b.p.
80–84° (65 mm.),
n25D 1.4094 (Note
13).
2. Notes
2.
Commercial reagent grade pyridine was used. The checkers used material available from Allied Chemical Corporation, B and A grade.
3. To avoid the accumulation of excess, unchanged
chromium trioxide and rapid temperature rise when it does react,
the initial temperature of the pyridine should never be below 10°.
5. A glassine paper cone or glass funnel inserted in the drying tube neck of the flask during additions proved satisfactory, provided the cone or funnel was replaced frequently. The paper must be discarded carefully, since it may inflame. Adding the
chromium trioxide from a flask through rubber tubing proved dangerous because it caused local excesses of the oxide below and in the neck of the flask.
Pyridine added to
chromium trioxide spontaneously ignites causing spot fires that extinguish themselves rapidly if the
pyridine temperature is below 20° and stirring is efficient. Such fires should and can be avoided.
6. Since the complex itself loses
pyridine under reduced pressure and darkens with surface decomposition, it should not be stored under vacuum or over acidic drying agents. Minimal exposure to the atmosphere is required to prevent hydration of the complex. The checkers found that a free-flowing product was obtained on drying for one hour.
8. If the complex does not dissolve in
dichloromethane, forming a red solution, either the complex has been hydrated in handling, or the
dichloromethane is not anhydrous.
9. After the alcohol and complex are thoroughly mixed, the mixture may be stirred near its surface to avoid fouling of the stirrer by the thick, chromium-containing reduction product. Alternatively, the mixture may be swirled periodically to collect the reduction product on the side of the flask.
11.
1-Heptanol, obtained from Aldrich Chemical Company, Inc., was distilled before use, b.p.
176°.
12. A second washing with
100 ml. of 5% hydrochloric acid will reduce the amount of
pyridine present in the final product without significantly decreasing the yield.
13. The product shows a strong band at 1720 cm.
−1 (C=O) in the IR. GC analysis indicated a purity of about 94–98%, with
pyridine as the major impurity.
3. Discussion
Chromic acid, in a variety of acidic media, has been used extensively for the oxidation of primary alcohols to aldehydes but rarely has provided aldehydes in greater than 50% yield.
5 Chromium trioxide in
pyridine was introduced as a unique, nonacidic reagent for alcohol oxidations and has been used extensively to prepare ketones,
6 but has been applied with only limited success to the preparation of aldehydes. While
2-methoxybenzaldehyde was obtained in
89% yield,
4-nitrobenzaldehyde and
heptanal were obtained in
28% and
10% yields, respectively.
7
Using the preformed
dipyridine chromium(VI) oxide in
dichloromethane, the rate of chromate ester formation and decay to the aldehyde
8 is enhanced at least twentyfold over the rate observed in
pyridine solution.
4 Isolation of products is facile, and aldehydes appear to be relatively stable to excess reagent. The reagent has been used extensively to prepare acid-sensitive aldehydes, particularly intermediates in the total synthesis of prostaglandins
9 and steroids.
10 An 85% yield was reported for the conversion of
2-vinylcyclopropylcarbinol to the aldehyde.
11 Although excess reagent is required for the oxidations (usually sixfold), the reaction conditions are so mild and isolation of products so easy that the complex will undoubtedly find broad use as a specialty reagent. Isolation of the complex can be avoided by
in situ preparation of the
chromium oxide/
pyridine complex.
12
Other general syntheses of aldehydes from primary alcohols involve the use of
dimethyl sulfoxide13 with a dehydrating agent such as
dicyclohexylcarbodiimide and
phosphoric acid (or
pyridinium trifluoroacetate),
14 diethylcarbodiimide,
15 or
sulfur trioxide.
16 Alternatively,
dimethyl sulfoxide has been used with derivatives of the alcohol such as the
chloroformate,
17 the iodide,
18 and the tosylate.
19 Tertiary butyl chromate20 and
lead tetraacetate in
pyridine21 have been employed to oxidize aliphatic primary alcohols to aldehydes, while
manganese dioxide22 has been used to prepare aromatic and α,β-unsaturated aldehydes. More recently,
pyridinium chlorochromate,
pyridinium dichromate and
chromium trioxide-3,5-dimethylpyrazole complex have been reported
23 to be effective reagents for the oxidation of primary alcohols to aldehydes in aprotic solvents.
This preparation is referenced from:
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved