A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1933, 13, 56
DOI: 10.15227/orgsyn.013.0056
[Acetonitrile, methoxy-]
Submitted by J. A. Scarrow and C. F. H. Allen.
Checked by Reynold C. Fuson and Charles F. Woodward.
1. Procedure
This preparation must be carried out in a hood having good suction. Methyl sulfate has a high vapor pressure in spite of its high boiling point and is very poisonous. Ammonia is a specific antidote and should be kept on hand to destroy any of the ester accidentally spilled. It is advisable to wash the hands in dilute ammonium hydroxide frequently.
In a 1-l. three-necked, round-bottomed flask, fitted with a stirrer, a thermometer for reading low temperatures (Note 1), and a dropping funnel, are placed 98 g. (2 moles) of pulverized sodium cyanide (Note 2) and 200 cc. of water. The stirrer is started, and 60 g. of paraformaldehyde (2 moles) (Note 3) is added in small quantities until the temperature rises to 20–25° and the sodium cyanide has dissolved. The flask is then surrounded by a freezing mixture, and the temperature is kept below 25° during the introduction of the remaining paraformaldehyde.
Two hundred cubic centimeters (270 g., 2.1 moles) of technical methyl sulfate is placed in the dropping funnel, and, when the temperature inside the flask has dropped to 13°, a 20- to 30-cc. portion of the sulfate is added. An exothermic reaction should set in; the ice bath is removed, if necessary, to get the reaction to start (Note 4). When the temperature begins to fall, the remainder of the methyl sulfate is admitted at such a rate as to keep the temperature at 12–15°; this takes at least twenty minutes. When the addition is complete the mixture is stirred an additional forty minutes; during this time the temperature will drop to about 5°. The stirrer is stopped, and the oily, upper layer is separated at once (Note 5). The lower, aqueous layer is returned to the flask and methylated as before with a second 200-cc. portion of methyl sulfate (Note 6).
The oily, upper layer is dried with 10 g. of anhydrous sodium sulfate (Note 7) and is distilled under diminished pressure. For this purpose an efficient fractionating column (Note 8) is used. The portion boiling below 70° at 15 mm. is mainly methoxyacetonitrile and weighs 60–70 g. The upper layer from the second methylation is treated in a similar manner; the distillate weighs 55–60 g. The residue in the distilling flask is methyl sulfate and is used in a subsequent run (Note 9).
The crude fractions are combined and distilled at atmospheric pressure through a good column; about 95 per cent distils at 118–122° as a colorless liquid. The methoxyacetonitrile so prepared weighs 100–110 g. (70–77 per cent of the theoretical amount).
2. Notes
1. A 30- to 35-cm. thermometer reading from −50 to +50° is most convenient since the graduations used are then outside the flask.
2. Potassium cyanide gives poorer results.
3. An equivalent amount of commercial formalin solution can be used with equally good results, provided that allowance is made for the volume of water—the total volume must not exceed 200 cc.
4. The reaction usually starts immediately; occasionally it does not start until the mixture becomes warm.
5. If the mixture is allowed to stand, the temperature rises to 40–50°, a red color develops, and the yield drops to almost nothing.
6. Recovered methyl sulfate can be used without purification.
7. No drying agent is completely satisfactory; sodium sulfate does the least harm.
8. The authors found a Glinsky column most satisfactory. A capillary tube reaching to the bottom of the flask for the admission of air is essential to prevent bumping. In the redistillation a piece of porous plate is sufficient for this purpose.
9. The density of the residual liquid in two runs was found to be 1.31, 1.32. The pure ester has a density of 1.35.
3. Discussion
Methoxyacetonitrile has been prepared by methylating hydroxyacetonitrile with methyl sulfate;1 by treating chloromethyl ether with cuprous or mercuric cyanide;2 and by dehydrating methoxyacetamide with phosphorus pentoxide.3 The procedure described is a modification of that of Polstorff and Meyer.1
This preparation is referenced from:

References and Notes
  1. Polstorff and Meyer, Ber. 45, 1911 (1912); Slater and Stephen, J. Chem. Soc. 117, 312 (1920); Malkin and Robinson, ibid. 127, 372 (1925).
  2. Gauthier, Ann. chim. phys. (8) 16, 302, 306 (1909).
  3. Kilpi, Z. physik. Chem. 86, 671 (1914).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

cuprous or mercuric cyanide

ammonia (7664-41-7)

formalin (630-08-0)

sodium cyanide (143-33-9)

sodium sulfate (7757-82-6)

potassium cyanide (151-50-8)

sulfate (14808-79-8)

ammonium hydroxide (1336-21-6)

methyl sulfate (75-93-4)

chloromethyl ether (542-88-1)

Acetonitrile, methoxy- (1738-36-9)

hydroxyacetonitrile (107-16-4)

methoxyacetamide (16332-06-2)

phosphorus pentoxide (1314-56-3)

paraformaldehyde (30525-89-4)