CS238140B1 - A method for recovering 2-propanol in the production of chloramphenicol - Google Patents

Abstract

The method of regeneration of 2-propanol in the production of chloramphenicol consists in obtaining a distillate from the mixture after reduction of 1-(4-nitrophenyl)-2-acetamido-3-hydroxypropanone and subsequent decomposition, or from the waste liquors after this reaction by distillation, to which 0.05 to 1 part by weight of an organic solvent, for example benzene or toluene per 1 kg of this distillate is added, then a heterogeneous azeotrope is distilled from the mixture by single-stage distillation or rectification at a temperature of 30 to 80 °C and atmospheric pressure, which is further divided into an aqueous and organic phase, the organic phase is returned to the azeotropic rectification, while the aqueous phase is returned to the mixture for decomposition, or to the waste liquors for further distillation, a distillation residue containing 2-propanol, 2-propyl acetate, organic solvent residues and a maximum of 7% by weight. of water is returned to the mixture for absoluteness after the reduction of 1-(4-nitrophenyl)-2-acetamido-3-hydroxypropanone, and the thus absolute mixture is used as a solvent for the preparation of aluminum chloro-2-propoxyalane for the next production batch.

Description

The highest consumption of 2-propanol in the production of the antibiotic chloramphenicol is at the degree of Merwein Pondorf reduction of 1- (4-nitro) phenyl-2-acetamido-3-hydroxypropanone (HMK) at about 280 kg per 100 kg of starting HMK.

About 60 kg of absolute 2-propanol can be distilled off from this amount after the reduction. A further portion can be obtained after decomposition of the reaction mixture with acid or base water by distillation and a further amount by distillation of the waste liquors after filtration of 1- (4-nitrophenyl) -2-amino-1,3-propanediol hydrochloride, is the product of HMK reduction, subsequent decomposition of the reduction mixture and deacetylation of the intermediate 1- (4-nitrophenyl) -2-acetamido-1,3-propanediol.

However, the 2-propanol thus obtained cannot be reused for reduction because it contains approximately 9 to 20 wt. water. Of the series of absolutizations of this aqueous 2-propanol, it seems to be the most suitable method for the reaction to be eliminated by the reaction mixture after reduction.

After the reduction, the aqueous 2-propanol obtained from the previous batches is returned to the reaction mixture and then distilled off, absolutely distilled with a max. Water content of 4. The disadvantage of this method is the relatively low discharge capacity of the reduction mixture. kg of absolute 2-propanol / and technical problems with high viscosity of the reducing mixture during the absolutization. The following method of 2-propanol recovery contributes to solving these problems:

The aqueous 2-propanol obtained by distillation from the decomposed reducing mixture as well as from the waste liquors is more or less close to the azeotropic mixture and thus the composition does not change much by the new distillation or rectification.

In addition to water, these distillates may contain 2-propyl acetate, acetone, acetic acid, which complicates the possibility of obtaining reliable liquid-vapor equilibrium data. A fundamental change in this equilibrium is achieved by the addition of an azeotropic agent from a number of aromatic hydrocarbons such as benzene or toluene.

In this case, an aromatic hydrocarbon, water, 2-propanol or 2-propyl acetate, acetone and acetic acid appear in the vapor phase and a new ternary or quaternary azeotrope is obtained with a lower boiling point than the original binary, or ternary azeotrope.

This new azeotrope contains more water than the original mixture, and thus the bottoms residue is depleted by water, so that a lower water content of 2-propanol can be obtained in the bottoms residue.

In addition, the distilled azeotrope is heterogeneous and can therefore be separated into aqueous and organic phases and, by appropriately arranged reoyl, reduce the losses of both 2-propanol and the solvent added in this method.

In particular, the organic phase with the aromatic hydrocarbon is returned to the aneotropic distillation and the aqueous phase to the waste liquor or to the decomposition mixture for further use in a subsequent batch, where it is distilled with the other 2-propanol by conventional distillation.

2-Propanol with optional 2-propyl acetate content and 1 to 7 wt.% Is then left in the distillation residue after azeotropic distillation or rectification. water. Since the absolute capacity of the reduction mixture is given by the ratio of water contained in the aqueous, regenerating 2-propanol and aluminum in the reduction mixture and further, after azeotropic distillation, the water content is reduced by at least twice, one batch can regenerate at least 200 kg of 2-propanol per 100 kg of starting HMK.

This absolute 2-propanol containing 2-propyl acetate and toluene or benzene can be used as a solvent for the preparation of aluminum chloro-2-propoxyalan to carry out the HMK reduction in the next production batch.

This process can be used to dewater any aqueous 2-propanol solutions. The principle of the method is explained in more detail in the following examples.

Example 1

Of the 600 ml waste liquor after filtration of the crude hydrochloride, 200 ml of a 75 wt. 2-propanol, 10 wt. 2-propyl acetate, 13 wt. water and 2 wt. unidentified substances.

50 ml of toluene were then added to the obtained distillate and the mixture was rectified on a column of 23 perforated plates and a reflux ratio of 1: 3. The resulting azeotrope was separated into two phases, of which the organic composition was 8% water, 20% 2-propanol, 72% toluene, and the aqueous phase 67% water, 30% 2-propanol and 3% toluene / wt. percent/.

2% of water was found in the distillation residue. All distillation residue (205 ml) was poured onto a reducing mixture prepared from 30 g HMK. 170 ml of 2-propanol containing 0.17% water were then distilled off from the mixture.

Example2

The reduction mixture, prepared from 30 g HMK with a total weight of 105 g, was quenched with 110 ml conc. hydrochloric acid, 30 ml of water, and 3 ml of the aqueous phase of Example 1. 21 ml of aqueous 2-propanol containing 17 wt. water, 2 wt. acetone, 1% higher boiling admixtures / e.g. aromatic ketones], 9% 2-propyl acetate.

The hydrochloride was further crystallized from the residue, which after drying was 22 g.

To 21 ml of distillation of the obtained 2-propanol was added 7 ml of toluene, followed by azeotropic rectification. 18 ml of distillation residue containing 3% water were obtained.

The entire residue was poured into a reducing mixture prepared from 30 g HMK from which 14 ml of 2-propanol containing 0.06% water was distilled off. To the distillation residue were added 20 ml of water, ml of the aqueous phase from azeotropic distillate and 110 ml of hydrochloric acid.

Then, 23 ml of aqueous 2-propanol was distilled off, and 23 g of hydrochloride were then crystallized from the distillation residue.

Example 3 ml of water was mixed with 360 ml of 2-propanol, 36 ml of 2-propyl acetate and 250 ml of carbon tetrachloride. The mixture was rectified on a laboratory column of 1 m length and 2.5 mm diameter. 10 m filled with Raschig rings of size 4. 10 with a reflux ratio of 1: 5.

The distillation residue (294 ml) consisted of 98 wt. 2-propanol, 1.9 wt. 2-wt. 2-propyl acetate and 0.1 wt. water. (Carbon tetrachloride was not indicated in the rest). The distillate was separated into aqueous and organic phases, the first of which contained 77% by weight. water and the other 1 wt. water.

The distillation residue was directly used to prepare aluminum chloro-2-propoxyalan which was used as a reducing agent.

Example 4

A mixture of 43 ml of water, 360 ml of 2-propanol, 36 ml of 2-propyl acetate and 250 ml of chloroform was rectified under the conditions of Example 3. The distillation residue (302 ml) contained 97.5% 2-propanol, 2.2% 2-propyl acetate and 0.3% water.

Example 5

A mixture of 43 ml of water, 390 ml of 2-propanol, 200 ml of cyclohexane. The distillation residue (315 ml) contained 2% water.

Example 6

A mixture of 43 ml of water, 390 ml of 2-propanol, 400 ml of 2-propyl acetate was rectified as in Example 3. The distillation residue (322 ml) contained 1% water, 96% 2-propanol.

Claims (2)

SUBJECT OF THE INVENTION Process for the regeneration of 2-propanol in the production of chloramphenicol, characterized in that a distillate is obtained from the mixtures after the reduction of 1- (4-nitrophenyl) -2-acetamido-3-hydroxypropanone and subsequent decomposition, to which 0.05 to 1 wt. part by weight of organic solvent, for example benzene or toluene per 1 wt. part of this distillate, then the heterogeneous azeotrope is distilled from the mixture by a single-stage distillation or rectification at a temperature of 30 to 80 ° C and atmospheric pressure, which is further separated into aqueous and organic phases, the organic phase returning to azeotropic rectification % of a blend for decomposition, optionally into waste liquors for further distillation; The water is returned to the mixture for reduction after the reduction of 1- (4-nitrophenyl) -2-acetamido-3-hydroxypropanone, and the mixture thus obtained is used as a solvent to prepare aluminum chloro-2-propoxalan for the next batch. 2. A process according to claim 1, characterized in that 0.05 to 0.3 wt. part of benzene or toluene is introduced into 1 wt. A portion of the distillate obtained by distillation of the mixture after reduction of 1- (4-nitrophenyl) -2-acetamido-3-hydroxypropanone and subsequent decomposition or from waste liquors thereafter is rectified and the distilled azeotrope is separated, the organic phase returning as reflux and the aqueous phase is removed.