RU2072349C1 - Process for preparing ortho- or para-nitrobenzaldehyde and 2-nitro-2-oxymethylpropane diol-1,3 - Google Patents

Abstract

FIELD: synthesis of medicinal agents. SUBSTANCE: 2-nitro-2- oxymethylpropane diol and ortho- or para- nitrobenzaldehyde. Yields are 97, 99 and 100% respectively. Reagent 1: ortho-beta-dinitrostyrene. Reagent 2: formaldehyde. Reaction conditions: in the presence of NaOH. EFFECT: more efficient preparation process. 2 tbl

Description

 The invention relates to chemical technology for the production of nitrobenzaldehyde isomers: ortho-nitrobenzaldehyde or para-nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3, which are intermediate products in the synthesis of a number of drugs.

Известен ряд методов получения нитробензальдегидов. Практический интерес представляют следующие.

A number of methods for producing nitrobenzaldehydes are known. The following are of practical interest.

Obtaining nitrobesaldehydes by oxidation of nitrotoluene with various oxidizing agents, for example sodium dichromate [1]
Obtaining nitrorbenzaldehydes by oxidation of nitrobenzaldehydes, for example, copper oxide [2]
Obtaining nitrobenzaldehydes by oxidation of nitrobenzyl alcohols, for example potassium permanganate [3]
Obtaining nitrobenzaldehydes by oxidation of nitrocinnamic acids or their esters, for example nitric acid [4]
Reduction of nitrobenzoic acid with formic acid [5]
Obtaining a mixture of nitrobenzaldehyde isomers by nitration of benzaldehyde [6]
Alkaline hydrolysis of nitrate of para-nitrobenzyl alcohol gives para-nitrobenzaldehyde [7]
Treatment of para-β-dinitrostyrene with concentrated sulfuric acid gives a mixture of para-nitrobenzaldehyde and para-nitrobenzoic acid [8]
Oxidation of b-dimethylamino-para-nitrostyrene with oxygen at elevated temperature [9,10]
The main disadvantages of the above methods for producing nitrobenzaldehydes are: low yield of target products, the complexity of technological processes, the formation of a large amount of production waste.

 The aim of the invention is to increase the yield of nitrobenzaldehydes, simplifying the process and the full use of reaction products.

 The goal is achieved in that ortho-nitrobenzaldehyde and para-nitrobenzaldehyde are obtained by treating, respectively, ortho-b-dinitrostyrene and para-b-dinitrostyrene with an aqueous solution of formaldehyde in the presence of an alkaline catalyst: sodium or potassium hydroxides, soda or borax.

 As a result of this reaction, nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3 are formed.

 The proposed method provides the production of ortho-nitrobenzaldehyde or para-nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3 in quantitative yield.

 The formaldehyde used for this reaction is almost completely consumed for the formation of 2-nitro-2-hydroxymethylpropanediol-1,3.

 The method provides the quantitative conversion of the starting compounds to the target products and eliminates the formation of by-products requiring recycling.

 Methods for producing ortho-nitrobenzaldehyde, para-nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3 are given in the examples.

 Dinitrostyrenes are quite stable in acidic environments. In an alkaline environment, dinitrostyrenes are in equilibrium with nitrobenzaldehyde and nitromethane.

Реакция является обратимой и в щелочном водном или водно-спиртовом растворе быстро устанавливается равновесие. Состояние равновесия зависит от концентрации щелочи, температуры и использованного растворителя.

The reaction is reversible and equilibrium is quickly established in an alkaline aqueous or hydroalcoholic solution. The equilibrium state depends on the concentration of alkali, temperature and the solvent used.

 A change in these parameters does not lead to a complete shift of the equilibrium towards the formation of nitrobenzaldehyde. The product of this reaction is always a mixture of nitrobenzaldehyde and the starting dinitrostyrene.

In addition, with prolonged exposure or increase in temperature above 60 ^o C, the reaction products are gummed. When nitrobenzaldehydes are distilled off from an alkaline solution with water vapor, the yield is 40–50% of the theoretically possible; the remaining dinitrostyrene is ground.

 When dinitrostyrene is added to the suspension in water, in the presence of alkali, formaldehyde, the latter interacts with equilibrium nitromethane to form 2-nitro-2-hydroxymethylpropanediol-1,3, which leads to a shift in equilibrium to the right and an increase in the concentration of nitrobenzaldehydes.

При добавлении 3 моль формальдегида на моль динитростирола равновесие полностью смещается в сторону образования нитробензальдегида и 2-нитро-2-оксиметилпропандиола-1,3, обеспечивая выход орто-нитробензальдегидов 98-100% теоретически возможного.

With the addition of 3 mol of formaldehyde per mole of dinitrostyrene, the equilibrium is completely shifted towards the formation of nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3, providing an output of ortho-nitrobenzaldehydes of 98-100% theoretically possible.

 A decrease in the amount of formaldehyde leads to a decrease in the yield of nitrobenzaldehydes.

 An increase in the amount of formaldehyde from 3 to 10 mol per 1 mol of dinitrostyrene does not affect the yield of nitrobenzaldehydes.

 Deviation from the interval of 0.1-0.5 mol of alkali per 1 mol of dinitrostyrene leads to a decrease in the yield of nitrobenzaldehydes.

 The influence of process parameters on the yield of ortho-nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3 is presented in table. 1, para-nitrobenzaldehyde in table. 2.

 The identification of ortho-nitrobenzaldehyde, para-nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3 was carried out on the basis of the data of elemental analysis, IR spectral analysis and gas chromatography. The content of the main substance in the obtained products was determined by gas chromatography.

 Example 1

19.4 g (0.1 mol) of ortho-β-dinitrostyrene are sprinkled with 100 ml of an aqueous solution containing 9.0 g (0.3 mol) of formaldehyde and 0.8 g (0.02 mol) of NaOH at 20 ^o The suspension was heated to 60 ^° C and held at this temperature with stirring for 60 minutes.

After exposure, it was cooled to 20 ^{° C.} and the crystalline product was filtered off, washed with 50 ml of water on a filter, and dried.

Received 15.5 g of product with a melting point of 45 ^o C. the Content of ortho-nitrobenzaldehyde 99.3% Yield 100% of theoretically possible.

 After separation of ortho-nitrobesaldehyde, the filtrate was acidified with sulfuric acid ≈ 1 ml to pH 2-3 and 300 ml of toluene was added. Azeotropic mixture was distilled off until complete removal of water, toluene was periodically returned to the cube.

 17.2 g of a product containing 2.4 g of sodium bisulfite and 14.8 g of 2-nitro-2-hydroxymethylpropanediol-1,3 was filtered off. Yield 98% of theoretically possible. The product was treated with a mixture of chloroform and ethyl acetate, sodium bisulfite was filtered off, and after evaporation of the filtrate, 14.8 g of 2-nitro-2-hydroxymethylpropanediol-1.3 was obtained (experiment 19, table 1).

 Example 2

Analogously to example 1, with the exception of the amount of NaOH 0.4 g (0.01 mol) and kept for 120 minutes at 60 ^o C.

 The output of ortho-nitrobenzaldehyde 95.2% of theoretically possible. The yield of 2-nitro-2-hydroxymethylpropanediol-1.3 is 90% (experiment 15, table 1).

Example 3
Analogously to example 1, except for the amount of KOH 1.68 g (0.03 mol).

 The yield of ortho-nitrobenzaldehyde is 100% of theoretically possible. The yield of 2-nitro-2-hydroxymethylpropanediol-1.3 is 98% (experiment 22, table. 1).

 Example 4

Analogously to example 1, except that used 19.0 g (0.05 mol) of Na ₂ B ₄ O ₇ .

 The yield of ortho-nitrobenzaldehyde is 99% of the theoretically possible. The yield of 2-nitro-2-hydroxymethylpropanediol-1.3 97% (experiment 23, table. 1).

 Example 5

38.8 g (0.2 mol) of para-b-dinitrostyrene was sprinkled with 200 ml of an aqueous solution containing 18.0 g (0.6 mol) of formaldehyde and 1.6 g (0.04 mol) of NaOH at 20 ^o The suspension was heated to 60 ^{° C.} and held at this temperature for 60 minutes. It was cooled to 20 ^° C. and the crystalline product was filtered off. Washed with 100 ml of water and dried. Received 30.6 g of product with a melting point of 104 ^o C. the Content of para-nitrobenzaldehyde 98.7% Yield 100% of theoretically possible.

 After separation of para-nitrobenzaldehyde, the filtrate was acidified with sulfuric acid ≈ 2 ml to pH 2-3 and 300 ml of toluene was added.

 The azeotropic mixture was distilled off until water was completely removed, periodically returning toluene to the cube.

 34.4 g of a product containing 4.8 g of sodium bisulfite and 29.6 g of 2-nitro-2-hydroxymethylpropanediol-1.3 was filtered off. Yield 98% of theoretically possible (experiment 17, table. 2).

 Example 6

 Analogously to example 5, with the exception of 3.36 g (0.03 mol) of KOH were used.

 The yield of para-nitrobenzaldehyde 99% 2-nitro-2-hydroxymethylpropanediol-1.3 97% of theoretically possible (experiment 18, table. 2).

 Example 7

Except for example 5, 0.8 g (0.02 mol) of NaOH was used and held for 120 min at 60 ^° C. The yield of para-nitrobenzaldehyde 95.0%; the yield of 2-nitro-2-hydroxymethylpropanediol 1.3 1.3% from theoretically possible (experiment 15, tab. 2).

Claims (1)

A method of producing ortho- or para-nitrobenzaldehyde and 2-nitro-2-hydroxymethylpropanediol-1,3, based on the nitro-derivative styrene at elevated temperature, characterized in that ortho- or para-β-dinistyrene is used as the nitro-derivative, which is treated with water formaldehyde at 60 100 ^o C in the presence of an alkali catalyst, for example sodium hydroxide or potassium carbonate or sodium borate, in a molar ratio of 1 2 6 0.1 0.5, respectively, followed by isolation by filtration or ortho paranitrobenzaldegida under Islenyev filtrate mineral acid to pH 2 3, the removal of water by azeotropic distillation and isolating the 2-nitro-2-1,3-oksimetilpropandiola.

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