CS200367B1 - Method for the continuous production of 5-nitrofurane derivatives - Google Patents

Description

The invention relates to a process for the continuous production of 5-nitrofuran derivatives of the general formula

wherein R represents a group of formula-CH₂-OCQCHg -CH QH _O ~, -CH (0C0CHg) _second

5-Nitrofuran derivatives have antimicrobial effects. They are used for the production of pharmaceuticals and for the production of non-antibiotic animal performance stimulators.

The nitration of furan derivatives with acetylnitrose takes place as an electrophilic addition to form a stable addition intermediate which can be easily converted to the corresponding 5-nitrofuran derivative by elimination of acetic acid.

5-Nitrofuran derivatives are most often prepared by a batch process of nitration of a furan derivative with acetyl nitrate and a batch decomposition of an addition nitration intermediate by an organic or inorganic base.

A disadvantage of these processes is that the nitration of the furan derivative is preceded by the preparation of the nitration mixture from acetic anhydride and nitric acid. The active ingredient of the nitration mixture is acetyl nitrate, which can be explosively decomposed even at a slightly elevated temperature. The batch process generally works with large volumes of the reaction mixture. Nitration of the furan ring is an exothermic reaction

200,367 (about 146 kO / mol). Addition of the furan derivative to the prepared nitration mixture can result in local overheating and initiation of explosive decomposition of acetyl nitrate. A disadvantage of the batch decomposition procedure of the nitration addition intermediate is that the required pH for the elimination reaction is only achieved after all the base has been added. This increases the reaction time and reduces the performance of the production equipment.

The effect of the explosive decomposition of actlyl nitrate can be reduced by adding an inert solvent such as a chlorinated aliphatic hydrocarbon (U.S. Patent No. 3,013,023). Maarish Patent No. 151,479 describes nitration of a furan derivative by a scorch process but simultaneously adding nitric acid and a forane derivative to acetic anhydride. This procedure eliminates the danger of decomposing acetyl nitrate to a minimum. The disadvantage of the process is a batch design.

Ca. U.S. Pat. No. 1,154,5S solves the nitration of a furan derivative by adding acetyl nitrate by continuously feeding nitric acid and acetic anhydride to the scrubbed reactor. The resulting nitration mixture is continuously fed into the circulating reactor together with a continuous feed of the phthirane derivative, where the actual nitration takes place. A disadvantage of this process is the separate preparation of the refractory mixture, which remains a potential danger of explosive decomposition.

German Offenlegungsschrift No. 2,523,759 discloses a process for preparing 5-nitrofurfuraldiacetate by continuously feeding nitric acid in a mixture with sulfuric acid and furfural or furfuraldiacetate in a mixture with acetic anhydride. Vznikajíc! the nitration addition intermediate is continuously fed together with water and aqueous sodium hydroxide solution to the water present in the final volume reactor. A disadvantage of this process is the technology using a finite volume decomposition reactor which needs to be cooled first so that the temperature of the reaction mixture does not exceed 15 ° C and after the completion of the dosing of all the rectants, thus ending the process continuity. Another disadvantage of the described process is a flow reactor which, in the case of continuous nitration, does not disturb the complete reaction of the incoming rectants. The yield of the continuous nitration thus performed is lower (76%) as compared to the yields over the SO% given in the example for the dicontinuous nitration. Also the throughflow rate of nitrates is low. . .

The above disadvantages of the described processes for the production of 5-nitrofuran derivatives substantially reduce the process of continuously producing the 5-nitrofuran derivatives of the formula

wherein R represents a group of the formula -CH ₂ -OCCOCH _3, CHg-OH, -CH (OCCH ₃ ) ₂ , as defined above, characterized in that the furan derivative, acetic anhydride, cyeelir and nitric acid at a concentration of 65 to 100 and the acid catalyst is fed simultaneously to the nitration factor, which is either a circulating reactor or a reciprocating reactor, in a molar ratio of 1: 3 to 10: 1 to 2: 0.01 to 0. At a reaction temperature of from -15 to 5 ° C, the resulting reaction mixture is continuously withdrawn from the nitration reactor and enters the reactor and piston by reaction through the reaction mixture to decompose the nitration addition intermediate by simultaneously introducing an aqueous solution of inorganic base in an amount necessary to reach pH 3 to 5 at a temperature of 30 to 80 ° C while holding the reaction mixture in the reactor for 2 to 60 minutes, after which the reaction mixture leaving the reactor is withdrawn to separate the reaction product, such as the acid catalyst used is, for example, perchloric acid, phosphoric acid, p-toluenesulfonic acid, and preferably sulfuric acid. The acid catalyst is fed in a mixture with nitric acid or a mixture with acetic anhydride. Inorganic bases are used, for example, alkali carbonate, calcium carbonate, alkaline phosphate and preferably alkaline hydroxide.

An advantage of the process for the preparation of the 5-nitrofuran derivatives according to the invention is the high output of the production equipment in totally continuous design, which guarantees safe and simple production with the possibility of maximum utilization of control and automation elements. Another advantage is to increase the yield from 76% to 86%,

He did

A circulating reactor or a piston reactor of a 200 ml reaction mixture is charged with 50 to 100 ml of acetic anhydride. The acetic anhydride is cooled to -10 ° C and 62 g / h of fuming nitric acid and concentrated sulfuric acid and 500 g / h of acetic anhydride and furfural are simultaneously introduced. Aoethanhydride, furfural, nitric acid and sulfuric acid are fed in a molar ratio of 4.235: 0.708: 0.961 ϊ 0.015. The reaction temperature is maintained at -10 to -5 ° C. The reaction mixture continuously leaving the nitration reactor is fed to the bottom of the reactor with a piston movement of a 200 ml reaction mixture together with a continuously coming 260 g / h aqueous sodium hydroxide solution (sodium hydroxide 47 g, water 213 g). The decomposition reaction takes place at a temperature of 60 to 63 ° C with a residence time in the reactor of 10 to 15 minutes. The reaction mixture continually leaving the decomposition reactor is fed to a 200 ml circulation reactor where 5-nitrofurfural diacetate is continuously crystallized at -5 to 0 ° C. The continuously leaving suspension is subjected to centrifugation separation. After washing with cold water to a pH of the filtrate of 5.5 to 6 and after complete centrifugation, it is dried at a temperature of up to 60 ° C in the absence of daylight.

Yield. The 5-nitrofurfural diacetate is 14.8 g / h (86 calculated on furfural). The melting point is 90-92 ° C.

Example 1 and d 2

The procedure and molar ratios of the reactants are the same as in Example 1. The difference is that furfurylacetate is used instead of furfural. Furfurylacetate is fed in a mixture with acetic anhydride. This mixture is fed at < 31 g / h.

The yield of 5-ritropurfuryl acetate was 70% based on furfurylacetate.

Example 3

The process and the molar ratios of the reactants are the same as in Example 1. It is distinguished in that the furfurel milled uses furfuryl alcohol which is fed to the mixture with acstanhydride. This mixture comes in an amount of 501 g / h. The yield of 5-nitropurfuryl alcohol is 65%, calculated on furfuryl alcohol.

Example 4

The operating procedure of the punolar ratios of the reactants is the same as in Example 1. The difference is that in the case of fuming nitric acid, 65% nitric acid is used in an amount of 92 g / h.

The yield of 5-nitrofurfural acetic acid is 45%, calculated on furfural.

Claims (3)

A process for the continuous production of 5-nitrofuran derivatives of the formula wherein R is -CH ₂ -OCCOCH 3, -CH ₂ -OH, -CH (CCOCH ₃ ) _g from a furan derivative, acetic anhydride, nitric acid in the presence of an acid catalyst, characterized in that the furan derivative, acetic anhydride, nitric acid of 65-100% and a. the acid catalyst is fed simultaneously to a nitration reactor which is either a circulating reactor or a piston-type reactor in a molar ratio of 1; to 3 to 10 to 1 to 2 to 0.01 to 0.05 at a reaction temperature of -15 to 5 ° C, the resulting reaction mixture is continuously discharged from the nitration reactor and added to the piston reactor of the reaction mixture to decompose the nitracs edition intermediate. at the same time by introducing an aqueous solution of the inorganic base in an amount necessary to achieve a pH of 3 to 5 at 30 to 80 ° C at the reaction of the reaction mixture leaving the reactor for 2 to 60 minutes, after which the reaction mixture leaving the reactor continuously is discharged to separate the reaction product. 2. Process according to claim 1, characterized in that the acid catalyst ee is introduced in a mixture with nitric acid or in a mixture with acetic anhydride. 3. The process according to claim 1, wherein the furan derivative is fed alone or in admixture with acetic anhydride.