Synthesis of diacetone-L-sorbose

Full text of DOI:10.1023/A:1010448500102

Pharmaceutical Chemistry Journal
Vol. 35, No. 4, 2001
SYNTHESIS OF DIACETONE-L-SORBOSE
1
1
1
1
M. A. Nadtochii, L. E. Burova, I. B. Vasil’eva, and T. A. Melent’eva
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 35, No. 4, pp. 52 – 53, April, 2001.
Original article submitted June 8, 1990.
Diacetone-L-sorbose (DAS) is an intermediate product in
the synthesis of ascorbic acid. DAS is obtained by acetona-
ting L-sorbose in the presence of a catalyst. Possible catalysts
are oleum, zinc chloride, copper sulfate, sulfonic acids, and
ion exchange resins. In addition to DAS, the process of
sorbose acetonation yields 1,2- and 2,3-monoacetonesorbose
cooled down to – 15°C again and held at this temperature for
1 h. Under these conditions, the yield of DAS reaches 81%
and the tar formation decreases to 7% (Table 1). The same
process using additionally ground sorbose (with a particle
size below 0.25 mm) yields 86% of DAS and 5% of tar.
A no less important factor is the presence of water which
forms during the acetonation reaction and can be additionally
brought in with the initial reagents. In the presence of water,
the yield of DAS may significantly decrease as a result of hy-
drolysis. This circumstance imposes an important require-
ment on the reagents: the water content must not exceed
0.1% in sorbose and 0.3% in acetone, and the oleum concen-
(
1,2- and 2,3-MAS) [1]:
H
CH3
H
HO
H
O
OH
HO
H
O
O
C
CH3
+
[
H ]
H
H
H
H
HO
H
HO
H
(
CH ) CO
CH OH
CH2
O
3 2
2
OH
OH
L-Sorbose
1,2-Î-Isopropylidene-a-L-sorbopyranose
tration must be not less than 18% SO . The amount of oleum,
3
which is added for binding water formed in the course of
acetonation, is very important: an increase in the oleum leads
to intensification of the process, whereas a decrease favors
DAS hydrolysis by the unbound water.
H C
3
H C
C
CH3
3
H
C
CH3
O
O
+
H
H O, [H ]
O
2
O
H
O
H
H C
H
O
H
2
CH OH
2
H C
It was found that the yield of DAS increases with the rel-
ative content of acetone (Table 2). An increase in the acetone
to sorbose (A/S, v/w) ratio from 12 : 1 to 15 : 1 leads to a
(
CH ) CO
2
CH OH
3
2
2
O
C
O
OH
HO
CH3
H C
3
2,3-MAS
DAS
7% increase in the DAS yield. However, this implies an in-
crease in the volume of acetone to be regenerated. The influ-
ence of the A/S ratio on the acetonation process was studied
under the optimum (–15°C, +25°C) temperature conditions.
The optimum A/S ratio in this regime is 12 : 1.
The acetonation process is accompanied by a side reac-
tion whereby the condensation of two acetone molecules
yields mesityl oxide. To the present, factors affecting the
course of the acetonation reaction and the DAS yield are in-
completely clear. Since the synthesis of DAS in domestic
plants is catalyzed by oleum, we have also studied the pro-
cess in the presence of this catalyst.
TABLE 1. Effect of Temperature on the L-Sorbose
Acetonation Process
In the first stage, we studied the effect of temperature on
the sorbose acetonation reaction. The experiments were per-
formed with non-comminuted sorbose (particle size,
Temperature
Process
DAS
Tar
regime, °C duration, h
yield, %
yield, %
0
.25 mm) because many of the domestic plants use this ma-
3
4
3
2
–
–
–
0
0.8
0.7
54.0
30.2
73.6
70.0
77.5
81.0
80.2
29.2
35.8
13.4
17.0
10.8
7.2
terial without additional grinding. It was established that the
optimum temperature conditions are the following: the pro-
cess is initiated at – 15°C, after which the temperature is
gradually increased to 25°C. At this temperature sorbose dis-
solves in acetone during 2 – 3 h. Finally, the reaction mass is
0
0
0
2.5
2.5
15, + 25
1 – 3
1 – 1.5
1 – 2.5
15, + 25
15, + 25
7.8
1
State Research Institute of Vitamins, State Unitary Enterprise, Moscow,
Russia.
Note: Sorbose/acetone/oleum ratio, 1 : 12 : 0.5.
229
0
091-150X/01/3504-0229$25.00 © 2001 Plenum Publishing Corporation

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30
M. A. Nadtochii et al.
TABLE 2. Effect of the Acetone to Sorbose (A/S) Ratio of the
Diacetone-L-sorbose (DAS) Yield
TABLE 3. Diacetone-L-sorbose Isolation under Various Condi-
tions
Acetonation
Process
Degree
A/S, ml/g
DAS yield, %
temperature, °C
duration, min
Extractant,
DAS con- of DAS
Procedure
salting-out reagent
tent, %
isolation,
%
1
0 : 1
– 15, + 25
– 15, + 25
– 15, + 25
– 15, + 25
– 15, + 25
150
150
120
120
100
78.8
79.3
80.5
81.5
87.1
1
1 : 1
Chloroform
Double extraction
94.66
92.14
96.0
99.0
96.5
96.3
1
1
1
2 : 1
3 : 1
5 : 1
(
2 : 1)
Double extraction
2 : 1)
Double extraction
2 : 1)
Toluene
(
Trichloroethylene
(
Since the yield of DAS is accompanied by the formation
4
4% aqueous NaOH
Salting-out for 2 h
Salting-out for 18 h
83.2
86.6
94.0
of monoacetonesorbose, it is necessary to separate these
products. There are several possible methods to separate
mono- and diacetonesorbose. The first is to extract DAS with
the aid of an organic solvent such as ether, chloroform, ben-
zene, toluene, or trichloroethylene. Another possibility is to
salt out DAS with an alkali. We performed a special compar-
ative experiment on the separation of DAS and MAS by the
extraction and salting-out methods (Table 3). The initial so-
lution was the neutralized acetone solution obtained from the
Shchelkovo Vitamin Plant. The content of DAS and MAS in
the residues obtained upon evaporating the extracts in vac-
uum was determined by gas chromatography.
44% aqueous NaOH
84.33
EXPERIMENTAL PART
To 275 ml of acetone at –15°C was added dropwise
5 ml of oleum containing 18% SO . To this solution was
1
3
added 25 g of sorbose and the mixture was stirred and heated
to 25°C, after which stirring is continued until compete dis-
solution of sorbose. After stirring for about 2 h, the reaction
mass is cooled to –15°C and kept at this temperature for 1 h.
Then the solution is neutralized with an 8% sodium hydrox-
ide solution and allowed to stand until layer separation. The
aqueous sodium sulfate solution is used to crystallize sodium
sulfate. The aqueous-acetone solution containing DAS and
MAS is treated in a film-rotary evaporator to distill off ace-
tone and then mesityl oxide. According to the gas chroma-
tography (GC) data, the residue (30.66 g) contains 28.45 g
DAS (yield, 81.3%), no 1,2-MAS, and traces of 2,3-MAS.
The sold residue is dissolved in 40 ml water and extracted
As is seen from Table 3, the content of DAS in the prod-
uct obtained by extraction with an organic solvent is
9
2 – 96% and the degree of extraction is 96 – 99%. The
product obtained by salting out with an alkali solution con-
tains 83 – 84% of DAS and only 94% of DAS is isolated af-
ter an 18-h treatment.
As a result, we selected the following procedure for the
exaction of DAS. First, the reaction mass is neutralized by an
8
% alkali solution. Upon separation of the layers, acetone
(
2 ´ 140 ml) with trichloroethylene. Then the solvent is dis-
tilled off to leave a residue (26.74 g) containing (GC data)
6.10 g of DAS; DAS yield upon extraction, 96.3%.
and mesityl oxide are distilled off from the water–acetone
phase and the residue is dissolved in water. Finally, DAS is
extracted with an organic solvent.
2
Thus, we have established that the decisive factors in the
process of L-sorbose acetonation are the temperature regime
and the acetone-to-sorbose ratio. Optimum conditions for the
isolation of diacetone-L-sorbose were determined.
REFERENCES
1. V. M. Berezovskii, Vitamin Chemistry [in Russian], Pishchevaya
Prom-st, Moscow (1973), p. 39.