A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1940, 20, 74
DOI: 10.15227/orgsyn.020.0074
[Glucononitrile, D-, pentaacetate]
Submitted by H. T. Clarke and S. M. Nagy.
Checked by W. E. Bachmann and Wayne Cole.
1. Procedure
To 350 ml. of anhydrous methanol contained in a 1-l. three-necked round-bottomed flask, to which is attached a reflux condenser protected by a drying tube, is added 20 g. (0.87 gram atom) of sodium (Note 1) in large pieces. The reaction is kept under control by cooling the flask in a pan of ice water. To the resulting solution of sodium methoxide is added a solution (Note 2) of 61 g. of hydroxylamine hydrochloride (0.88 mole) in 20 ml. of water; during the addition the mixture is swirled in order to avoid spattering. After 20 minutes the mixture is cooled to 0° and filtered with suction. The sodium chloride is washed with 350 ml. of anhydrous methanol. The combined filtrate and washings are warmed to 65° in a 3-l. round-bottomed flask, and a solution of 100 g. of finely powdered commercial crystalline glucose monohydrate (0.50 mole) in 200 ml. of warm 25% aqueous methanol is added, with stirring. The resulting solution is held at 65° for 2 hours and then concentrated under reduced pressure until no further distillate is obtained; the residue weighs 155–160 g. The resulting syrup (Note 3) is diluted with 300 ml. of methanol and again distilled, and this process is repeated once (Note 4).
A mixture of 100 g. of powdered, anhydrous sodium acetate and 677 ml. of 90% acetic anhydride (Note 5) is heated on a steam bath in a 3-l. round-bottomed flask under an efficient reflux condenser. Without interrupting the heating a solution of the syrupy glucose oxime in 50 ml. of glacial acetic acid and 100 ml. of cold acetic anhydride is added through a dropping funnel to the hot mixture (Note 6); this requires about 1 hour (Note 7). Heating is continued for another hour, and the bulk (380–420 ml.) of the acetic acid and any unchanged acetic anhydride is distilled under reduced pressure from a water bath. The residue is immediately stirred into 2 l. of cold water, stirred occasionally during the first 3 hours, and allowed to stand overnight.
After the mixture has been chilled to 0°, the brown, crystalline mass is filtered with suction and washed with 500 ml. of water. The solid is dissolved in 300 ml. of hot 95% ethanol, and the solution is heated with 10–15 g. of Norit for 5 minutes and filtered with suction. The filtrate is gradually cooled to 0°; the crystals are filtered with suction and washed with 20 ml. of cold ethanol. The weight of the first crop is 90–93 g. A second crop is obtained by concentrating the mother liquor under reduced pressure to 25 ml., boiling the solution with Norit, filtering, and chilling the filtrate to 0°. The total yield of colorless pentaacetyl d-glucononitrile melting at 82.5–83.5° is 95–96 g. (50%).
2. Notes
1. In preparing free hydroxylamine, a little less than the theoretical amount of sodium is employed to avoid the presence of free alkali in the reaction mixture.
2. The hydroxylamine hydrochloride dissolves in the small amount of water when the mixture is warmed to about 125°.
3. The isolation of glucose oxime is unnecessary in this preparation.
4. The distillation with methanol serves to remove water almost completely.
5. If acetic anhydride of a higher concentration is available, correspondingly smaller quantities may be employed.
6. The viscous, syrupy glucose oxime dissolves with difficulty, and it may be necessary to warm the mixture slightly. If this is done, a pan of ice water should be at hand in order to cool the mixture should the temperature begin to rise rapidly.
7. In the process described in the literature, the oxime, sodium acetate, and acetic anhydride are allowed to react without dilution, a condition which frequently leads to an uncontrollably violent reaction.
3. Discussion
The above method for preparing glucose oxime is the modification of that of Jacobi1 developed by Wohl,2 who first converted the oxime into the pentaacetyl glucononitrile by means of acetic anhydride. The latter reaction was later employed for the same purpose by Zemplén and Kiss.3
Pentaacetyl glucononitrile has also been prepared by dehydration of pentaacetyl gluconamide with phosphorus oxychloride.4
This preparation is referenced from:

References and Notes
  1. Jacobi, Ber., 24, 696 (1891).
  2. Wohl, Ber., 26, 730 (1893).
  3. Zemplén and Kiss, Ber., 60, 165 (1927).
  4. Ladenburg, Tischler, Wellman, and Babson, J. Am. Chem. Soc., 66, 1217 (1944).

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

ethanol (64-17-5)

acetic acid (64-19-7)

methanol (67-56-1)

acetic anhydride (108-24-7)

sodium acetate (127-09-3)

sodium chloride (7647-14-5)

sodium methoxide (124-41-4)

Norit (7782-42-5)

Phosphorus Oxychloride (21295-50-1)

sodium (13966-32-0)

Hydroxylamine hydrochloride (5470-11-1)

hydroxylamine (7803-49-8)

glucose monohydrate (14431-43-7)

pentaacetyl glucononitrile,

Glucononitrile, D-, pentaacetate (6272-51-1)

glucose oxime

pentaacetyl gluconamide