Download (direct link):
1. The success of the reaction depends largely on the type of agitation used. A stainless-steel stirrer of the anchor type with a gas-tight rubber or metal-graphite bearing serves well because of its strength. It should be operated at high speed in the first part of the reaction in order to powder the sodium; in the second stage vigorous stirring is not so essential, but the solid and liquid phases should be mixed efficiently.
2. The toluene may be dried by refluxing it over metallic sodium for several hours. It is distilled from the sodium into a receiver protected from the air by a calcium chloride tube.
3. The excess sodium should amount to about 11 g. If the sodium remains divided, it is removed by filtering the hot mixture through glass wool.
4. It is not advisable to leave the separatory funnel attached to the flask during the long period of stirring which follows, as the constant, heavy vibration tends to loosen the connection. As soon as it has been used, the funnel should be replaced by a tightly fitting cork stopper.
5. The commercial grade (m.p. 61-63°) of monochloroacetic acid should be ground and thoroughly dried over concentrated sulfuric acid in a vacuum desiccator for two days. The yield was lowered by about 10 per cent when the chloroacetic acid was used without previous drying.
6. The toluene layer, containing the menthol formed in the reaction, is saved for the recovery of both the toluene and the menthol, which are separated by distillation under atmospheric pressure. The /-menthol collected at 210-212° (corr.) amounts to 150-225 g.
3. Method of Preparation
/-Ì enthoxyacetic acid has been prepared only by the action of sodium menthoxide upon monochloroacetic acid.1
1 Frankland and O’Sullivan, J. Chem. Soc. 99,2325 (1911); Rule and Todd, ibid. 1931, 1929.
CH / \
I I -J- SOCl2 —>
CH / \
² ³ + íà + so2
CH / \
Submitted by Ì. T. Leffler and A. E. Calkins.
Checked by R. L. Shriner and Ñ. H. Tilford.
A 1-1. three-necked round-bottomed flask is mounted on a steam cone and is fitted with a 250-cc. separatory funnel and a reflux condenser connected to a trap (Note 1) for absorbing gases. In the flask is placed 325 g. (198 cc., 2.73 moles) of thionyl chloride (Note 2), and to it is added, during the course of one hour, 125 g. (0.58 moles) of /-menthoxyacetic acid (p. 52). The flask is shaken frequently during the addition of the acid and, if necessary, is warmed to start the reaction. When all the acid has been added
(Note 3), the reaction mixture is refluxed gently for five hours. After the reaction is complete, the excess of thionyl chloride is removed by distillation on the steam bath (Note 4) and the residue is distilled under reduced pressure. The yield of /-menthoxy-acetyl chloride boiling at 117-120°/3 mm. (120-125°/5 mm.), [a]o = —89.6°, amounts to 115-118 g. (Note 5) (85-87 percent of the theoretical amount). The product turns dark on standing; it should be stored in a glass-stoppered amber bottle.
1. The gas absorption trap shown in Org. Syn. Coll. Vol. 1, 1941, 97, may be used.
2. The commercial grade (b.p. 74-78°) of thionyl chloride was used.
3. Owing to the high viscosity of the acid, it is desirable to rinse the separatory funnel with a little thionyl chloride which is then added to the reaction mixture.
4. The recovered thionyl chloride may be redistilled for future runs. It is best to remove the last traces of thionyl chloride by heating the crude product to about 140° under the vacuum of the water pump.
5. The submitters report the same yields (per cent) when twice the amounts of materials are used.
3. Method of Preparation
The procedure given above is adapted from that described by Read and Grubb.1 No other methods for the preparation of /-menthoxyacetyl chloride have been described.
1 Read and Grubb, J. Soc. Chem. Ind. 51, 330T (1932).
J + Zn(CN)2 + 4HC1 2
j % ZnCb