Checked by Max Tishler and Arthur J. Zambito.
1. Procedure
In a
5-l., three-necked, round-bottomed flask equipped with a
rubber- or mercury-sealed mechanical stirrer and a
reflux condenser carrying a
drying tube are placed
340 g. (4 moles) of cyanoacetic acid (Note
1) and
2 l. of anhydrous ether. To the stirred solution,
834 g. (4 moles) of phosphorus pentachloride is added in portions through the third neck of the flask, which is sealed between additions. The mixture is cooled occasionally with an
ice bath to prevent excessive refluxing, and, after the addition is complete, stirring is continued for 0.5 hour or until the
phosphorus pentachloride dissolves completely. The reflux condenser is removed and replaced with apparatus for downward distillation (Note
2), and the
ether is distilled from a
water bath at 50–60° (Note
3), after which most of the
phosphorus oxychloride is removed at reduced pressure (20–25 mm. with a bath temperature of 55–65°) (Note
4), the
receiver being cooled in an
ice-salt bath. The red, oily residue is dissolved in
200 ml. of benzene and the
benzene and residual
phosphorus oxychloride distilled under reduced pressure. This operation is repeated with
200 ml. of fresh benzene to ensure complete removal of
phosphorus oxychloride (Note
5). The residue is then cooled to room temperature (Note
6) and is transferred to a
500-ml. pressure-equalized dropping funnel for immediate use in the following step.
The same 5-l. flask used in the preceding step is used again, without washing; it is fitted with a reflux condenser carrying a drying tube, a sealed mechanical stirrer, and the dropping funnel containing the acid chloride. In the flask are placed
296 g. (4 moles) of dry t-butyl alcohol (Note
7) and
484 g. (4 moles) of dimethylaniline in
600 ml. of anhydrous ether (Note
8). The acid chloride is added dropwise to the stirred solution, the mixture being cooled occasionally with an ice bath to prevent excessive refluxing. After the addition is complete, the reaction mixture is refluxed for 2 hours and then stirred gently at room temperature for 15 hours. Two liters of water is added with stirring, and the mixture is filtered with suction through a
Büchner funnel fitted with a matting of glass wool (Note
9). The matting is washed with three
250-ml. portions of ether (Note
10). After separation of the combined ethereal layers, the aqueous layer is extracted twice with
250-ml. portions of ether. The combined
ether solutions are washed with successive portions of
2N sulfuric acid (a total of 1 l.) until free of
dimethylaniline, then with two
200-ml. portions of 2N sodium carbonate solution, and dried over
sodium carbonate. After removal of the
ether by distillation, the residue is transferred to an alkali-washed flask and distilled at reduced pressure through a
20-cm. alkali-washed Vigreux column (Note
11). The yield of colorless product is
355–378 g. (
63–67%) boiling at
67–68°/1.5mm. (
90°/10 mm.,
54–56°/0.3 mm),
nD20 = 1.4198.
2. Notes
1.
Cyanoacetic acid of 98% purity, obtained from Kay-Fries Chemicals, Inc., was used.
2. A Claisen head with a condenser leading into a flask with a suction arm connected to a drying tube is suitable. Ground-glass joints are recommended.
3. A large bucket containing water and placed on a
steam bath serves as a suitable water bath. The temperature is easily controlled between the limits mentioned.
4. The
ether is removed from the receiving flask before the
phosphorus oxychloride is distilled. A drying tube should be placed between the suction arm of the flask and the
water pump, which serves as the source of suction. The reaction mixture may be stirred during the distillation of the oxychloride, or the stirrer may be removed and replaced with a capillary ebulliator tube to which is attached a ballon filled with dry
nitrogen.
5. The checkers found that the distillation with
benzene ensures a more complete removal of
phosphorus oxychloride which, if still present, interferes in the subsequent step and a lower yield of product results.
6. The submitters found that on several occasions, when the residue was not cooled before transfer, it began to generate considerable heat while standing in the dropping funnel and resulted in the total carbonization of the acid chloride.
7. The submitters dried the
t-butyl alcohol by refluxing it over
calcium hydride overnight and distillation in a moisture-free apparatus. The checkers found that stirring the
t-butyl alcohol at 60–70° over
calcium hydride for several hours and then distilling the alcohol, using an air condenser, is a satisfactory procedure. When the
t-butyl alcohol is refluxed, the alcohol vapors condense and solidify (m.p.
24–25°) in the reflux condenser and cause clogging.
8. These reagents should be weighed out beforehand in order to prevent delay in commencing with this step.
9. The filtration removes some tarry resinous material which would otherwise interfere in the separation of the layers. The checkers found that unless the filtrate is recycled through the same matting several times, to remove practically all the tarry residue, the separation of layers and the subsequent extractions prove troublesome owing mainly to emulsion formation.
10. The checkers found that a considerable amount of product is withheld by the residue on the glass-wool matting. The product is extracted by placing the matting in a
beaker, stirring with
ether, and filtering. This procedure is repeated twice, and the
ether extracts are combined with the original filtrate.
11. The distilling flask and Vigreux column to be used should be washed with
25% aqueous sodium hydroxide solution, rinsed three times with water, and then dried. Alternatively, about
1 g. of anhydrous potassium carbonate may be added to the residue before distillation.
3. Discussion
The present preparation employs a method of considerable scope which gives much better yields and is considerably less laborious than other methods for the preparation of
t-butyl cyanoacetate. The compound is of specific interest since, for example, it may be used in any reaction where
ethyl cyanoacetate is used (condensation reactions, etc.), but it has the added advantage that the carbo-
t-butoxy group, which may serve in conjunction with the α-cyano group to activate the α-hydrogens (for cyanoethylations, etc.), may be later removed simply by pyrolysis of the compound.
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