CN102746185A - Preparation process of aromatic nitrile compound - Google Patents

Abstract

The invention discloses a preparation process of aromatic nitrile compounds. It uses alkylbenzene as the reaction solvent, cuprous iodide, potassium iodide and N,N'-dimethylethylenediamine as the combined catalyst, brominated aromatic hydrocarbon and potassium ferrocyanide under the protection of nitrogen at 120-170 Reaction at ℃ for 24-60 hours, then cooled to room temperature, filtered, the filtrate recovers the solvent, and then conducts vacuum fractionation or recrystallization to obtain the corresponding aromatic nitrile compound with high yield and high purity. Compared with the existing synthetic methods, the present invention has the following advantages: 1) mild reaction conditions; 2) short reaction process; 3) use of cheap non-toxic cyanation reagents; 4) very simple feeding and post-treatment, It is easy to recover the catalyst and realize industrialized large-scale production.

Description

A kind of preparation technology of aromatic nitrile compound

technical field

The invention relates to a preparation method of an organic synthesis intermediate, in particular to a preparation process of an aromatic nitrile compound.

Background technique

Aromatic nitrile compounds are important fine chemical intermediates, which can be hydrolyzed to prepare acids or reduced to amines, and are widely used in the fields of pharmaceuticals, pesticides, dyes, plastic additives and fine organic chemicals; important aromatic nitrile fine chemical intermediates The body includes the key intermediate of antidepressant citalopram 5-cyanophthalide, the key intermediate of antihypertensive drug sartan biphenyl, the intermediate of hydralazine drugs o-cyanobenzaldehyde, and the liquid crystal material 4'-alkyl -4-cyanobiphenyl and so on.

At present, there are three main process routes in the production of aromatic nitrile compounds at home and abroad: (1) elimination method; (2) ammoxidation method; (3) substitution method. The elimination method is to obtain aromatic nitrile compounds by amination of aromatic carboxylic acids or aldehydes under catalyst conditions and then dehydration elimination reaction. It has the characteristics of simple operation, high yield, rich raw materials and the ability to prepare fatty nitrile compounds. The disadvantages are corresponding The cost of aromatic carboxylic acids or aldehydes is relatively high, so this method is generally only suitable for the preparation of scientific research laboratories [Synth Commun, 1989(1), 189; EP790234, 1997; US 5618965, 1997; Mol Online, 1998, 12(3 ), 94]. The second method, the ammoxidation method, is the main method for the large-scale industrial production of aromatic nitriles. This method is to react methyl aromatic compounds with ammonia and oxygen under catalyst conditions. The catalysts used in the ammoxidation method are mostly V, Ti, cr, B, Mo and other oxides or mixtures of several oxides in different proportions [Chim.Ind., 1988,70(4), 58; DE254111,1988 ; Chim.Ind.74(30,183; EP525367, 1993]. This production method is characterized in that the source of alkylaromatic raw material is wide, and it is more favorable for large-scale production of aromatic nitrile derivatives with relatively simple structure. The disadvantage is that the reaction selectivity is slightly poor, and the reaction The conditions are harsh, and the aromatic hydrocarbon raw materials must have a methyl group at the corresponding position; and in the existing partial fine chemical intermediate aromatic nitrile compounds, their precursor methyl aromatic ring derivatives are not available as industrial products or are not suitable for preparation. On the contrary Their precursor halogenated aromatic hydrocarbons and halogenated heteroaromatic hydrocarbons are available in large quantities or should be prepared cheaply from industry, thereby preparing aromatic nitriles through cyanation reaction is another feasible approach in industrial production.The third method substitution method is Aromatic nitrile and heteroaromatic nitrile compounds can be obtained by substituting halogenated aromatic hydrocarbons with cyanation reagents. Traditional cyanation reagents include sodium cyanide (NaCN), potassium cyanide (KCN), TMSCN, Zn(CN) ₂ , CuCN , (CH ₃ ) ₂ C(OH)CN. Among them, NaCN and KCN are highly toxic; Zn(CN) ₂ and CuCN are highly toxic, and because they need to be used stoichiometrically, they will cause serious heavy metal pollution; TMSCN is easy to absorb moisture and is not easy to handle. Convenient, like (CH ₃ ) ₂ C(OH)CN, will release highly toxic hydrogen cyanide gas in the reaction process, causing serious environmental pollution [Tetrahedron, 1984, 40(9), 1433; J. Org. Chem ., 1979, 44(24),4443; JACS, 2003, 125(100, 2890, Org. lett. 2004, 6(170, 2837].

One of the main research strategies for new technologies in green organic chemistry is to use green reagents and catalysts with low pollution, high selectivity and high efficiency. Starting from the green organic synthesis reaction technology, the cyanation reaction of important halogenated aromatic hydrocarbons was selected as the research object, and the use of highly toxic reagents such as potassium cyanide, sodium cyanide and cuprous cyanide was avoided, and low-toxicity reagents were obtained at low prices. Green reagent Potassium ferrocyanide (which can even be used as a food additive) is a cyanation reagent. The research uses low-pollution, high-selectivity, high-efficiency and cheap metal catalysts and ligand systems to systematically develop the green color of fine chemical intermediates aromatic nitrile compounds. Synthetic commonality technology has important practical significance.

Contents of the invention

The purpose of this invention is to provide a kind of preparation technology of aromatic nitrile compound.

The preparation process of the aromatic nitrile compound of the present invention uses alkylbenzene as the reaction solvent, cuprous iodide, potassium iodide and N,N'-dimethylethylenediamine as the combined catalyst, brominated aromatic hydrocarbon and ferrocyanide Potassium chloride is reacted at 120-170°C for 24-60 hours under the protection of nitrogen, then cooled to room temperature, filtered, and the filtrate recovers the solvent and conducts vacuum fractionation or recrystallization to obtain the corresponding aromatic nitrile compound; said brominated aromatic hydrocarbon and The molar equivalent ratio of potassium ferrocyanide is 1:0.15～0.3, the consumption of cuprous iodide is 1%～20% molar equivalent of bromoarene, and the consumption of potassium iodide is 1～2 molar equivalent of cuprous iodide, The amount of N,N'-dimethylethylenediamine is 0.8 to 1.2 molar equivalents of brominated aromatic hydrocarbons;

The reaction formula is:

,

In the formula, R ¹ , R ² = hydrogen, trifluoromethyl, fluorine, nitro, amino, aldehyde, C ₁ to C ₄ hydrocarbon group or C ₁ to C ₄ hydrocarbon group, cyclohexyl or substituted cyclohexyl , aryl or substituted aryl, the substituent on the substituted aryl and the substituent on the substituted cyclohexyl are trifluoromethyl, fluorine, C ₁ to C ₄ hydrocarbon group or C ₁ to C ₄ Hydrocarbyloxy, R ¹ and R ² may be the same or different.

The reaction solvent alkylbenzene is mesitylene, ethylbenzene or xylene.

Compared with existing synthetic methods, the present invention has the following advantages:

1) Mild reaction conditions;

2) The reaction process is short;

3) Use cheap non-toxic cyanation reagents;

4) Feeding and post-treatment are very simple, easy to recover the catalyst, and easy to realize industrialized mass production.

Detailed ways

The following examples will help to understand the present invention, but are not limited to the content of the present invention:

Example 1

In a 100-liter reactor, add 30 liters of xylene, 30 moles of p-methylbromobenzene, 6 moles of potassium ferrocyanide, 0.573 kg (3 moles, 0.1 equivalent) of cuprous iodide, and 1 kg of potassium iodide in sequence under nitrogen protection. (6 moles, 0.2 equivalents), 2.64 kg of N,N'-dimethylethylenediamine (30 moles, 1.0 equivalents), stirred and reacted at 145°C for 50 hours under nitrogen protection, ended the reaction, cooled to room temperature, and filtered Recover the inorganic salt, recover the solvent xylene from the filtrate under reduced pressure, carry out fractional distillation on the residue to recover N,N'-dimethylethylenediamine, and obtain p-toluonitrile, the yield is 91%, white solid, mp 25- 26 °C; ¹ H NMR (CDCl3): 2.42 (s, 3H), 7.27 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 8.2 Hz, 2H); ¹³ C NMR (CDCl3): 21.8 , 109.3, 119.1, 129.8, 132.0, 143.6; IR (KBr):(CN) 2226 cm ^-1 ; EI-MS m/z : 117 (M+, 100).

Example 2

In a 100-liter reactor, add 50 liters of xylene, 30 moles of p-bromobiphenyl, 5.5 moles of potassium ferrocyanide, 0.573 kilograms (3 moles, 0.1 equivalent) of cuprous iodide, and 1 kilogram of potassium iodide ( 6 moles, 0.2 equivalents), 2.64 kg of N,N'-dimethylethylenediamine (30 moles, 1.0 equivalents), stirred and reacted at 150°C for 48 hours under nitrogen protection, ended the reaction, cooled to room temperature, and recovered by suction filtration Inorganic salt, the filtrate was decompressed to recover the solvent xylene and N,N'-dimethylethylenediamine, the residue was recrystallized from ethanol to obtain p-cyanobiphenyl, the yield was 71%, white solid, mp 81-82 °C ; ¹ H NMR (CDCl3): 7.39-7.53 (m, 3H), 7.56-7.62 (m, 2H), 7.66-7.75 (m, 4H); ¹³ C NMR (CDCl3): 110.8, 118.9, 127.2. 127.7, 128.6, 129.1,132.6, 139.1, 145.6; IR (KBr): (CN) 2225 cm-1; EI-MS m/z : 179 (M ⁺ , 100).

Example 3

In a 100-liter reactor, under nitrogen protection, add 40 liters of mesitylene, 30 moles of 4-bromo-4'-ethylbiphenyl, 6 moles of potassium ferrocyanide, 2.5 moles of cuprous iodide, and 5 moles of potassium iodide , 24 moles of N,N'-dimethylethylenediamine, stirred and reacted at 165°C for 48 hours under nitrogen protection, ended the reaction, cooled to room temperature, recovered inorganic salts by suction filtration, and recovered solvent mesitylene and N , N'-dimethylethylenediamine, the residue was subjected to high-vacuum fractional distillation to obtain liquid crystal intermediate 4-cyano-4'-ethylbiphenyl, the yield was 85%, mp73～74 ℃, clearing point 22 ℃, ¹ H NMR ( 400 MHz CDCl ₃ ): 1. 28 (m ,3 H ,-CH3 ) ,2. 74 (m ,2H ,-CH2-) ,7.36～7. 85 (m ,8H ,-Ar-)ppm .

Claims (2)

1. the preparation technology of an aromatic nitriles compound; It is characterized in that it is is reaction solvent with the korenyl, with cuprous iodide, potassiumiodide and N, N '-dimethyl-ethylenediamine is a combination catalyst; Aryl bromide and yellow prussiate of potash reacted 24-60 hour at 120-170 ℃ under nitrogen protection; Cool to room temperature subsequently filters, and filtrating is reclaimed and carried out vacuum fractionation behind the solvent or recrystallization obtains the corresponding aroma nitrile compounds; The molar equivalent ratio of said aryl bromide and yellow prussiate of potash is 1:0.15～0.3; The consumption of cuprous iodide is 1%～20% molar equivalent of aryl bromide; The consumption of potassiumiodide is 1～2 molar equivalent of cuprous iodide; N, the consumption of N '-dimethyl-ethylenediamine are 0.8～1.2 molar equivalent of aryl bromide;

Reaction formula is:

，

R in the formula ¹, R ²=hydrogen, trifluoromethyl, fluorine, nitro, amino, aldehyde radical, C ₁～C ₄Alkyl or C ₁～C ₄-oxyl, cyclohexyl or substituted cyclohexyl, aryl or substituted aryl, substituting group and the substituting group on the substituted cyclohexyl on the said substituted aryl are trifluoromethyl, fluorine, C ₁～C ₄Alkyl or C ₁～C ₄-oxyl, R ¹And R ²Can be identical or different.

2. the preparation technology of a kind of aromatic nitriles compound according to claim 1 is characterized in that said reaction solvent korenyl is sym-trimethylbenzene, ethylbenzene or YLENE.