RU2824124C1 - Method of producing 4-bromo-3-nitrobenzaldehyde - Google Patents

Abstract

FIELD: organic chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely to a method of producing 4-bromo-3-nitrobenzaldehyde, which can be used as an active component of chemical compositions, including as a polynucleophile cross-linking agent, as a starting substance for producing fluorescent dyes, anti-inflammatory preparations. Method of producing 4-bromo-3-nitrobenzaldehyde using concentrated solutions of sulfuric and nitric acids, contains treatment of 4-bromobenzyl alcohol with a mixture of concentrated solutions of sulfuric and nitric acids with molar ratio of 4-bromobenzyl alcohol : sulfuric acid : nitric acid 1:(20–30):(20–30) by mixing mixture at 20–25 °C for 1–1.5 hours, followed by treatment of the reaction mass with ice, filtration and drying.

EFFECT: obtaining 4-bromo-3-nitrobenzaldehyde using a simple and efficient method using minimum amounts of commercially available reagents.

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Description

The invention relates to the field of organic chemistry, namely, to a method for producing 4-bromo-3-nitrobenzaldehyde, which can be used as an active component of chemical compositions, including as a crosslinking agent for polynucleophiles, as a starting material for producing fluorescent dyes, anti-inflammatory drugs.

A method for obtaining 4-bromo-3-nitrobenzaldehyde by treating 4-bromobenzaldehyde with sulfuric and nitric acids at a molar ratio of 1:7.83:1.17 while stirring the reaction mixture for 1 hour at a temperature of 40 °C is known. The product is isolated by treating the reaction mass with ice, followed by filtration and drying. The yield of the product was 55% (Zapata-Morales J. R. et al. Synthesis and evaluation of antinociceptive and anti-inflammatory effects of nitroporphyrins // Med. Chem. Res. 2018. Vol. 27. No. 7. Pp. 1782-1791). Significant disadvantages of the method include the need to use 4-bromobenzaldehyde, which is unstable during storage, the need for strict temperature control, and a low yield of the target compound.

A method is known for obtaining 4-bromo-3-nitrobenzaldehyde by treating 4-bromobenzaldehyde with a mixture of sulfuric acid and sodium nitrate at a molar ratio of reagents of 1:20.42:1.19 while stirring the reaction mixture for 2 hours at a temperature of 10°C. The product is isolated by treating the reaction mass with ice, followed by filtration and drying. The yield of the product was 94% (US 8080566 B1). Significant disadvantages of the method include the need to use 4-bromobenzaldehyde, which is unstable during storage, and to carry out the reaction at a low temperature, which requires the use of special equipment.

A method is known for obtaining 4-bromo-3-nitrobenzaldehyde by treating 4-bromobenzaldehyde with a mixture of sulfuric acid and sodium nitrate at a molar ratio of reagents of 1:19.82:1.20 while stirring the reaction mixture for 20 minutes at a temperature of 10°C. The product is isolated by treating the reaction mass with ice, followed by filtration and drying. The yield of the product was 95% (US20020007059 A1). The disadvantages of the method include the need to use 4-bromobenzaldehyde, which is unstable during storage, and to carry out the reaction at a low temperature, which requires the use of special equipment.

The objective of the invention is to obtain 4-bromo-3-nitrobenzaldehyde in a simple and efficient manner using minimal amounts of commercially available reagents.

The problem set is solved in that in the method for obtaining 4-bromo-3-nitrobenzaldehyde, 4-bromobenzyl alcohol is treated with a mixture of concentrated solutions of sulfuric and nitric acids at a molar ratio of 4-bromobenzyl alcohol: sulfuric acid: nitric acid of 1: (20 - 30): (20 - 30) by stirring the mixture at 20 - 25 °C for 1-1.5 hours, followed by treating the reaction mass with ice, filtration and drying. The recommended conditions for obtaining 4-bromo-3-nitrobenzaldehyde have been established empirically and are also determined by the concepts of the process presented below. Commercially available 4-bromobenzyl alcohol and concentrated solutions of sulfuric and nitric acids are used to obtain 4-bromo-3-nitrobenzaldehyde. Using a 4-bromobenzyl alcohol: sulfuric acid: nitric acid molar ratio higher than 1:30:30 results in excessive and inefficient consumption of reagents. Using a 4-bromobenzyl alcohol: sulfuric acid: nitric acid molar ratio lower than 1:20:20 is ineffective due to low reagent conversion. Stirring the mixture for more than 1.5 h does not increase the yield of 4-bromo-3-nitrobenzaldehyde. Reaction time less than 1 h, as well as carrying out the reaction without sulfuric or nitric acid, results in a decrease in the conversion of 4-bromobenzyl alcohol to 4-bromo-3-nitrobenzaldehyde.

The analysis of the composition and structure of 4-bromo-3-nitrobenzaldehyde was carried out using elemental analysis (elemental analyzer "PE 2400", Perkin Elmer), infrared Fourier spectroscopy (spectrometer "Nicolet 6700", Thermo scientific) and nuclear magnetic resonance spectroscopy (spectrometer "AVANCE 500", Bruker).

The preparation of 4-bromo-3-nitrobenzaldehyde is illustrated by the following examples:

Example 1

A mixture of 128 ml (1.76 mol) of concentrated nitric acid, 98 ml (1.76 mol) of concentrated sulfuric acid and 11 g (0.059 mol) of 4-bromobenzyl alcohol was stirred for 1.5 h at 20°C. Then the reaction mixture was treated with 200 g of ice, the precipitate was filtered off and dried. Yield of 4-bromo-3-nitrobenzaldehyde: 13.03 g (96%). Found, %: C 35.14; H 1.82; N 5.86; Br 33.40. For the formula C ₇ H ₄ BrNO ₃ calculated, %: C 36.55; H 1.75; N 6.09; Br 34.74; O 20.87. NMR spectrum ¹ H (CDCl ₃ , δ, ppm): 7.96 (m, 2H, CH=CH); 8.32 (d, H, CH); 10.04 (s, 1H, COH); IR spectrum, cm ^–1 : 646, 1035, 1291, 1352, 1471, 1535, 1595, 1693, 2859, 3043, 3071.

Example 2

A mixture of 104 ml (1.44 mol) of concentrated nitric acid, 53 ml (0.94 mol) of concentrated sulfuric acid and 9 g (0.048 mol) of 4-bromobenzyl alcohol was stirred for 1 h at 25°C. The reaction mixture was then treated with 164 g of ice, the precipitate was filtered off and dried. Yield of 4-bromo-3-nitrobenzaldehyde: 8.08 g (73%).

Example 3

A mixture of 100 ml (1.38 mol) of concentrated nitric acid, 116 ml (2.07 mol) of concentrated sulfuric acid and 13 grams (0.069 mol) of 4-bromobenzyl alcohol was stirred at 20°C for 1 hour. The reaction mixture was then treated with 234 g of ice, the precipitate was filtered off and dried. Yield of 4-bromo-3-nitrobenzaldehyde: 10.16 g (64%).

The production method is simple to implement. It uses commercially available compounds, the method eliminates the need for preliminary synthesis of the starting materials, does not require complex equipment or additional auxiliary devices. A significant advantage of the claimed method for producing 4-bromo-3-nitrobenzaldehyde is the simplicity and technological effectiveness of the production process with fewer stages and a higher yield in contrast to known methods. The claimed method allows one to obtain 4-bromo-3-nitrobenzaldehyde on any industrial reactor equipment without additional improvements. 4-bromo-3-nitrobenzaldehyde can be used as an active component of chemical compositions, including as a crosslinking agent for polynucleophiles, as a starting material for producing fluorescent dyes and anti-inflammatory drugs.

Claims (1)

A method for obtaining 4-bromo-3-nitrobenzaldehyde using concentrated solutions of sulfuric and nitric acids, characterized in that 4-bromobenzyl alcohol is treated with a mixture of concentrated solutions of sulfuric and nitric acids at a molar ratio of 4-bromobenzyl alcohol: sulfuric acid: nitric acid 1: (20 - 30): (20 - 30) by stirring the mixture at 20 - 25 °C for 1-1.5 hours, followed by treating the reaction mass with ice, filtering and drying.