On the Issue of Converting the Batch Process for Amidopyrine Production to a Continuous One

I. P. Chashchin, V. I. Redekop, G. D. Spetstsi, M. S. Lantsman,
N. I. Lozbina

(Presented by the scientific seminar of the Department of Processes, Apparatuses, and Cybernetics of Chemical Production)

In connection with the increasing demand for medicinal preparations, there arises a need to increase their production. An increase in the output of preparations can be achieved in the following different ways:
a) by constructing new shops; b) by reconstructing old ones, i.e., by transferring them to a more advanced technology or by using more efficient equipment; c) by converting batch production processes to continuous ones.

Until the present time it has been considered that in the chemical-pharmaceutical industry, where preparations are produced mainly by fine chemical synthesis, and where production is of relatively small tonnage, taking into account the complexity of the processes, batch production schemes are unavoidable [1, 2, 3]. However, the conversion of multistage processes from batch schemes to continuous ones appears more progressive; moreover, this makes it possible to rigidly fix the technological parameters, eliminate heavy and harmful manual labor, and ultimately produce a high-quality product at higher labor productivity.

The present work pursues the goal of converting the production of amidopyrine from a batch scheme to a continuous one.

The production of amidopyrine is multistage, and each of its stages, in turn, is subdivided into separate technological operations. According to the technological scheme of the Anzhero-Sudzhensk Chemical-Pharmaceutical Plant, production is subdivided into the following stages:

1. Methylation of phenylmethylpyrazolone with methyl ester of benzenesulfonic acid.
2. Nitrosation of antipyrine benzenesulfonate with sodium nitrite.
3. Reduction of nitrosoantipyrine with a sulfite-bisulfite mixture.
4. Methylation of aminoantipyrine with formalin in the presence of formic acid.
5. First alcohol recrystallization of technical amidopyrine.
6. Second alcohol recrystallization of amidopyrine.
7. Third alcohol recrystallization of amidoantipyrine.
8. Drying of crude amidopyrine.

At present we are conducting studies on converting the first two stages to a continuous process, i.e., the first methylation and nitrosation.

After studying the physicochemical parameters of the technical raw material and intermediates, as well as carrying out certain physicochemical calculations [4, 5, 6], in order to select construction materials for the apparatus design of the process, we determined the contact angle of wetting of these materials by melts of PMP and BSKA on an apparatus of the design ...

P. A. Rebinder [7]. Design changes were introduced into the apparatus that made it possible to maintain the substances under study in the molten state.

The laboratory studies carried out also established the influence of various technological parameters on the crystallization of BSKA [8].

On the basis of an analysis of the existing production scheme and the data of physicochemical studies and calculations, we considered several variants of technological schemes for the first methylation in the production of amidopyrine.

The principal requirements in this case were: continuous metering of the starting raw material, continuous performance of the methylation reaction, continuous crystallization of BSKA, and continuous separation of BSKA crystals from the mother liquor.

The method of metering proposed by us differs from the existing one in that it makes it possible to carry out continuous metering instead of periodic metering. Piston metering pumps equipped with regulating devices were used as the metering apparatus, instead of the ordinary balances and measuring vessels used in the periodic production scheme. Continuous methylation is carried out in an apparatus—a reactor—having a jacket, a multisection stirrer, and an internal partition, which makes it possible to increase the path of the reactants entering the apparatus from below; i.e., a displacement reactor is proposed instead of the periodically operating mixing apparatus.

It is proposed to carry out the crystallization of BSKA in a continuously operating apparatus consisting of a combined screw and tower crystallizer. The combined design makes it possible to flexibly regulate the process of continuous crystallization and to reduce incrustation to a minimum. The crystallization time is reduced, in comparison with the existing process carried out in a periodic apparatus, from 24 hours to 0.5–1 hour.

It is proposed to separate BSKA crystals from the mother liquor in a continuously operating centrifuge with screw discharge of the crystals, instead of the existing ordinary three-column periodic centrifuges.

The total duration of the first methylation process according to the proposed continuous scheme is 2–3 hours instead of 30–36 hours in the existing one.

At present, the proposed scheme for the first stage of continuous methylation is being worked out at the Anzhero-Sudzhensk Chemical-Pharmaceutical Plant. The second stage of continuous nitrosation is undergoing laboratory tests.

REFERENCES

1. A. N. Nesmeyanov, N. A. Nesmeyanov. Principles of Organic Chemistry, vol. 1. “Khimiya,” 1969.

2. A. A. Petrov, Kh. V. Balyan, A. T. Troshchenko. Organic Chemistry. “Vysshaya shkola,” 1969.

3. A. N. Planovskii, D. A. Gurevich. Equipment for the Intermediates and Dyes Industry. Goskhimizdat, 1961.

4. Houben–Weyl. Methods of Organic Chemistry. Vol. 2. “Khimiya,” 1969.

5. Berl–Lunge. Chemical-Technical Methods of Investigation. GONTI, 1937.

6. V. I. Redekop, I. P. Chashin, G. D. Spetss, M. S. Lantsman. Determination of certain physicochemical properties of the starting products in the production of amidopyrine. Izvestiya TPI, (present collection).

7. I. N. Putilova. Manual for Practical Work in Colloid Chemistry. “Khimiya,” 1952.

8. L. N. Matusevich. Crystallization from Solutions in the Chemical Industry. Moscow, “Khimiya,” 1968.