Pharmaceutical Chemistry Journal

Vol. 39, No. 1, 2005

TECHNOLOGY OF PURIFICATION OF SYNTHETIC TOCOPHEROL ACETATE (VITAMIN E) É. Yu. Bulychev,1 Yu. A. Pisarenko,1 and M. K. Zakharov1 Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 1, pp. 37 – 38, January, 2005. Original article submitted November 1, 2004.

One possible solution to the complex problem of tocopherol acetate purification is offered by film distillation of technical vitamin E in a purification system comprising two hollow columns operating at a residual pressure of 20 Pa with a partial reflux of the distillate stream.

ing tight sealing of the rotating shaft at a low residual pressure in the working zone. We believe that the only reasonable solution to this complicated problem is offered by the method of continuous distillation in the run-down film regime. The theory, practical implementation, and methods of calculation of such apparatuses have been considered in [1]. Advantages of this distillation method are the simplicity of equipment, the short time of treatment in the zone of heating, the possibility of operation at arbitrarily low pressure, and the absence of rotating parts. It should be emphasized that the apparatus comprises hollow columns without plates, fillings, or other internal devices (capable of increasing the internal hydraulic resistance to the vapor flow and hindering the possibility of conducting the process under high vacuum conditions). Taking into account the aforementioned advantages of the proposed distillation method, we attempted to determine the working parameters of the setup so as to ensure the yield of a product with preset composition (not less than 97% of tocopherol acetate (compound I)) and a content of impurities (including a-tocopherol (compound II)) not exceeding 3%. The initial composition of a technical mixture to be purified is as follows (wt.%): compound I, 87.6; compound II, 2.4%; low-boiling components (isophytol, phytodienes, phytone, dehydroisophytol, dihydroisophytol, trimethylhydroquinone diacetate), 5.6%; high-boiling components (a-tocopherol spirodimer, resinous substances, oxidation and thermodestruction products), 4.4%. In order to solve the problem, we carried out a numerical experiment using a PRO/II program package. The multicomponent technical product was represented as a mixture of four fractions: (A) low-boiling substances (120 – 200°C/20 Pa); (B) compound II (215°C/20 Pa); (C) com-

An important problem encountered in the commercial production of synthetic tocopherol acetate (vitamin E) is related to the need to purify the technical product. This task is complicated by several factors: high viscosity and thermal lability of the medium; intense resin formation; the presence of a large amount of impurities, many of which are close to the target product in both structure and properties. At the same time, both Russian and international normative documentation places high requirements on the product: the content of tocopherol acetate must be not less than 96%, the proportion of impurities must not exceed 3%; the final product must not contain resinous substances producing coloration of the solution. The old method of vacuum fractionation traditionally used for the purification of technical vitamin E cannot meet the increasing requirements on the product quality. This is related to the low efficiency of simple distillation and to the unavoidable prolonged boiling of the bottom mixture, which leads to overheating, partial decomposition, and significant deterioration of the product quality. The number of alternative methods is very restricted. The conventional vacuum distillation cannot be used because of extremely low residual pressure. Indeed, at a maximum possible temperature of 220 – 230°C at the column bottom, the residual pressure in this zone must be within 0.1 – 0.2 Torr. In order to maintain these parameters, the hydraulic losses of the vapor flow in the filled column have to minimized (ultimately close to zero), which is hardly possible. The method of molecular distillation is inapplicable because of the low efficiency of single separation, high energy consumption, and considerable cost of equipment. The use of rotor film evaporators is hindered by the difficulty of provid1

Lomonosov State Academy of Fine Chemical Technology, Moscow, Russia.

37 0091-150X/05/3901-0037 © 2005 Springer Science+Business Media, Inc.

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É. Yu. Bulychev et at.

TABLE 1. Product Flows in the Film Distillation System of Tocopherol Acetate (I) Purification at a Residual Pressure of 20 Pa (0.15 Torr)

A À+Â+Ñ+D S1

S2

Flow

I B+C Â+Ñ+D S3

S4

II

D S5

Efficiency, kg/h Temperature, °C Fraction composition (mol.%): A B C D

S1

S2

S3

S4

S5

100.0 176.5

5.6 119.5

94.4 227.0

89.9 200.0

4.5 230.0

0.0560 0.0240 0.8760 0.0440

0.9999 – – –

– 0.0254 0.9280 0.0466

– 0.0267 0.9733 –

– – 0.0225 0.9775

Fig. 1. Schematic diagram of the system of technical tocopherol (I) acetate purification by the method of film distillation (see text for explanations).

pound I (220°C/20 Pa); and (D) high-boiling substances (225 – 240°C/20 Pa). We assumed that the film distillation of technical tocopherol acetate takes place in a cascade of hollow columns at a residual pressure of 20 Pa (0.15 Torr) and each column operates with partial reflux of the distillate flow. The system capacity with respect to the input mixture was 100 kg/h. Using the results of preliminary numerical experiments, we selected the scheme of product separation presented in Fig. 1. The parameters of this scheme were calculated assuming that a real multicomponent technical mixture can be modeled by a four-component mixture of higher fatty acids with various hydrocarbon chain lengths and close values of volatility. We used a reliable experimental data bank for the physicochemical properties of substances, which was necessary for consistent operation of the PRO/II system. According to this, various fractions of the mixture were modeled by the following fatty acids: lauric (fraction A), myristic (B), palmitic (C), and oleic (D). We have also tried to use model systems composed of other standard substances, having

properties even closer to those of the real products (with respect to the structure, boiling temperature, viscosity, density, heat capacity, etc.). However, these model mixtures consisted of compounds belonging to various classes. However, in purifying technical vitamin E, we deal with related compounds possessing close structures and properties. These considerations determined final choice of the model system. The results of calculations using the PRO/II program complex gave the following parameters of columns according to the scheme in Fig. 1. Column I: number of effective plates, n = 15; reflux index, R = 20; supply to the 7th plate from top. Column II: n = 20; R = 20; supply to the 14th plate from top. Data on the compositions and intensities of flows are presented in Table 1. The results of our model calculations show the principal possibility of purification of technical tocopherol acetate by means of the proposed technology. REFERENCES 1. M. K. Zakharov and V. V. Bulavtsev, Transfer Processes in Film Apparatuses, in: Scientific Works of the Academy of Fine Chemical Technology [in Russian], Moscow (2002), Issue 6, pp. 42 – 53.