Organic Syntheses, CV 5, 471
Submitted by John J. Ritter
1 and Joseph Kalish
2.
Checked by William G. Dauben and Alan Krubiner.
1. Procedure
Caution! This preparation should be conducted in a
hood because poisonous
hydrogen cyanide may be evolved.
A.
N-Formyl-α,α-dimethyl-β-phenethylamine. To a
2-l., three-necked, round-bottomed flask fitted with a
sealed stirrer carrying a
crescent-shaped blade, a
thermometer, an
addition funnel, and a
reflux condenser connected to a
trap containing
20% sodium hydroxide solution is added
500 ml. of glacial acetic acid (Note
1). The contents of the flask are cooled to 20° by means of an
ice bath, the addition funnel is temporarily replaced by a stopper, and to the stirred
acetic acid is added
110 g. (2 moles) of 95% sodium cyanide in small portions. The temperature of the mixture is maintained around 20°, and the addition requires about 20 minutes (Note
2). The addition funnel is replaced, and a previously prepared and cooled solution of
500 g. (272 ml., 4.9 moles) of concentrated sulfuric acid in
250 ml. of glacial acetic acid is added slowly, with stirring, the temperature of the mixture being kept at about 20° by means of an ice bath (Note
3). The ice bath is removed, and
300 g. (2 moles) of α,α-dimethyl-β-phenethyl alcohol (Note
4) is added over a 20-minute period during which the temperature of the mixture rises slowly to 35–45°. The reaction mixture is stirred for an additional 90 minutes (Note
5) and allowed to stand overnight. The amber-colored mixture containing some solid
sodium sulfate is aerated with
nitrogen for 2 hours
(Caution! In a hood), poured into 3 l. of ice water, and the supernatant oil separated. The aqueous phase is neutralized with
sodium carbonate and extracted with
600 ml. of ether. The ethereal extract is combined with the original oily supernatant, neutralized with
sodium carbonate, and dried over anhydrous
sodium sulfate. The solvent is removed under reduced pressure, and the residue is distilled to yield
230–248 g. (
65–70%) of product, b.p.
137–141° (2 mm.). Redistillation of the ether-containing fore-run yields up to an additional
14 g. of material.
B.
α,α-Dimethyl-β-phenethylamine. In a
3-l., three-necked, round-bottomed flask equipped with a
reflux condenser and a sealed stirrer are placed
246 g. (1.39 moles) of N-formyl-α,α-dimethyl-β-phenethylamine and
2.1 l. of 20% sodium hydroxide solution. The mixture is heated under reflux with vigorous stirring for 2.5 hours or until a test portion of the oily layer dissolves completely in cold
5% hydrochloric acid. The reaction mixture is cooled,
750 ml. of benzene is added, the mixture is stirred, and the
benzene layer is separated. The
benzene solution is shaken with a saturated
sodium chloride solution, the
benzene removed by distillation at atmospheric pressure, and the product distilled at reduced pressure to yield
155–165 g. (
75–80%) of
α,α-dimethyl-β-phenethylamine, b.p.
80–82° (10 mm.).
2. Notes
1. The reaction may be conducted in other solvents (e.g.,
dibutyl ether) or in the absence of solvent with some alteration in the order of mixing the reagents. The submitters find for this and a large number of similar preparations that
acetic acid generally is most convenient.
3. Care must be taken during the first part of the addition because the reaction is very exothermic.
5. The temperature may continue to rise during the initial portion of this period, but it is controlled by means of an ice bath to limit the temperature of the mixture to 45–50°.
3. Discussion
4. Merits of the Preparation
The present method is shorter and less laborious than previously described methods, and it gives better yields of material. The method, now known as the Ritter reaction, is one of considerable scope,
5 having been used with fair to excellent success with many tertiary alcohols or the corresponding alkenes, with
benzyl alcohol, and with some secondary alcohols. It has also been used with alkanes, alkadienes, alicyclic and spiro alcohols, alkyl chlorides, glycols, aldehydes, chlorohydrins, N-methylolamides, ethers, carboxylic acids, esters, ketones, and ketoximes. The Ritter reaction has been reviewed.
5 Another example of this reaction is given elsewhere in this volume.
6
This preparation is referenced from:
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