CN102746185A - Preparation process of aromatic nitrile compound - Google Patents

Abstract

The invention discloses a preparation process of an aromatic nitrile compound. According to the preparation process, alkylbenzene is used as a reaction solvent, copper iodide, potassium iodide and N, N'- dimethyl ethylenediamine are used as a combined catalyst, bromo-aromatic hydrocarbon reacts with potassium ferrocyanide in nitrogen at 120-170 DEG C for 24-60 hours to obtain a mixture, and then the mixture is cooled to room temperature to be filtered. After the solvent is recovered, a filtrate is processed through decompression fractionation or recrystallized to obtain the corresponding aromatic nitrile compound. An obtained product has the advantage of high yield and purity. Compared with the existing synthetic method, the preparation process has the advantages of mild reaction condition, short reaction process, utilization of cheap nontoxic cyano chemical reagent, simplicity in feeding and post treatment, easiness in recovery of the catalyst, and easiness in realization of industrial production.

Description

A kind of preparation technology of aromatic nitriles compound

Technical field

The present invention relates to the preparation method of organic synthesis intermediate, relate in particular to a kind of preparation technology of aromatic nitriles compound.

Background technology

The virtue nitrile compound is important fine-chemical intermediate, and both hydrolyzable prepared acid and also can be reduced into amine, was widely used in medicine, agricultural chemicals, dyestuff, additives for plastics and Fine Organic Chemical article preparation field; Important fragrant nitrile fine-chemical intermediate has antidepressant drug citalopram key intermediate 5-cyanophthalide, antihypertensive drug key intermediate sartanbiphenyl, the adjacent cyanobenzaldehyde of hydralazine class pharmaceutical intermediate, liquid crystal material 4 '-alkyl-4-cyanobiphenyl or the like.

At present, mainly contain three kinds of operational paths in the domestic and international fragrant nitrile compound production: (1) null method; (2) oxidation proceses of ammonia; (3) method of substitution.Null method is under the catalyzer condition, to be eliminated reaction and obtain fragrant nitrile compound through dehydration again through amination by aromatic carboxylic acid or aldehyde; Have simple to operate, yield is high, abundant raw material and can prepare characteristics such as aliphatic nitrile compound; Shortcoming is that the cost of corresponding aroma carboxylic acid or aldehyde is higher; Therefore this method generally only is suitable for preparation [Synth Commun, 1989 (1), 189 of scientific experiment chamber; EP790234,1997; US 5618965,1997; Mol Online, 1998,12 (3), 94].The second method oxidation proceses of ammonia is the main method that heavy industrialization prepares fragrant nitrile, and this method is that methyl aromatic substance and ammonia and oxygen are reacted.Mostly the oxidation proceses of ammonia catalyst system therefor is V, Ti, and cr, B, various oxide compounds such as Mo or several kinds of oxide compounds are pressed mixture [Chim.Ind., 1988,70 (4), 58 that different ratios is formed; DE254111,1988; Chim. Ind. 74 (30,183; EP525367,1993].These working method characteristics are that the alkylaromatic hydrocarbon raw material sources are wide, and are comparatively favourable for the simple relatively fragrant carbonitrile derivatives of scale operation structure, and shortcoming is that reaction preference is poor slightly, severe reaction conditions, and also aroamtic hydrocarbon raw material must have methyl in the corresponding position; And in the existing part fine-chemical intermediate virtue nitrile compound; Their precursor methyl aromatic derivatives does not have industrial goods and can supply maybe should not prepare; The assorted aromatic hydrocarbons of their precursor halogenated aryl hydrocarbon and halo then can supply maybe should prepare cheapness in a large number from industry on the contrary, thereby process cyanic acid prepared in reaction virtue nitrile is another feasible approach on the industrial production.The third method method of substitution is that halogenated aryl hydrocarbon and cyanic acid reagent carry out substitution reaction and obtains fragrant nitrile and assorted fragrant nitrile compound.Tradition cyanic acid reagent has sodium cyanide (NaCN), Potssium Cyanide (KCN), TMSCN, Zn (CN) ₂, CuCN, (CH ₃) ₂C (OH) CN.Wherein NaCN and KCN are hypertoxic; Zn (CN) ₂Big with CuCN toxicity, and, can cause serious heavy metal contamination because need stoichiometry to use; The easy moisture absorption of TMSCN is handled inconvenience, with (CH ₃) ₂C (OH) CN equally all can emit the prussic acid gas of severe toxicity in reaction process, cause severe 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 main research strategy that green organic chemistry new technology is carried out is to use green reagent and adopts low pollution, highly selective, catalyzer efficiently.Start with from green organic synthesis technology; The cyanic acid reaction of selecting important halogenated aryl hydrocarbon is a research object; Evade poisonous reagents such as using Potssium Cyanide, sodium cyanide and cuprous cyanide; With the green reagent yellow prussiate of potash of low toxicity cheap and easy to get (even can as foodstuff additive) is cyanic acid reagent; Low pollution, highly selective, cheap metal catalyzer and ligand system are efficiently adopted in research, and the synthetic common technology of green of system development fine-chemical intermediate virtue nitrile compound has important practical sense.

Summary of the invention

The preparation technology who the purpose of this invention is to provide a kind of aromatic nitriles compound.

The preparation technology of aromatic nitriles compound of the present invention; Be to be 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.

Described reaction solvent korenyl is sym-trimethylbenzene, ethylbenzene or YLENE.

The present invention compares with existing compound method, has the following advantages:

1) reaction conditions is gentle;

2) the reaction process flow process is short;

3) use cheap nontoxic cyanic acid reagent;

4) feed intake with aftertreatment all very simple, be easy to reclaim catalyzer, be easy to realize industrialized production.

Embodiment

Following examples will help to understand the present invention, but be not limited to content of the present invention:

Embodiment 1

In 100 liters of reaction kettles, add 30 liters of YLENE under the nitrogen protection successively, 30 moles to the methyl bromobenzene, 6 moles of yellow prussiate of potash, 0.573 kilogram (3 moles; 0.1 cuprous iodide equivalent), 1 kilogram of potassiumiodide (6 moles, 0.2 equivalent), 2.64 kilograms of N, (30 moles of N '-dimethyl-ethylenediamine; 1.0 equivalent), under nitrogen protection,, finish reaction, cool to room temperature 145 ℃ of stirring reactions 50 hours; Suction filtration reclaims inorganic salt, and filtrate decompression reclaims solvent xylene, and residue carries out fractionation can reclaim N, N '-dimethyl-ethylenediamine; And obtain to methyl benzonitrile productive rate 91%, white solid, mp 25-26 ° C; ¹H NMR (CDCl3): 2.42 (s, 3H), 7.27 (d, J=8.0 Hz, 2H), 7.54 (d, J=8.2 Hz, 2H); ¹³C 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).

Embodiment 2

In 100 liters of reaction kettles, add 50 liters of YLENE under the nitrogen protection successively, 30 moles to bromo biphenyl, 5.5 moles of yellow prussiate of potash, 0.573 kilogram (3 moles; 0.1 cuprous iodide equivalent), 1 kilogram of potassiumiodide (6 moles, 0.2 equivalent), 2.64 kilograms of N; N '-dimethyl-ethylenediamine (30 moles, 1.0 equivalents) 150 ℃ of stirring reactions 48 hours, finishes reaction under nitrogen protection; Cool to room temperature, suction filtration reclaims inorganic salt, and filtrate decompression reclaims solvent xylene and N, N '-dimethyl-ethylenediamine; Residue carries out ethyl alcohol recrystallization and obtains to cyanobiphenyl productive rate 71%, white solid, mp 81-82 ° C; ¹H NMR (CDCl3): 7.39-7.53 (m, 3H), 7.56-7.62 (m, 2H), 7.66-7.75 (m, 4H); ¹³C NMR (CDCl3): 110.8,118.9,127.2. 127.7,128.6, and 129.1,132.6,139.1,145.6; IR (KBr): (CN) 2225 cm-1; EI-MS M/z: 179 (M ⁺, 100).

Embodiment 3

In 100 liters of reaction kettles, add 40 liters of sym-trimethylbenzene under the nitrogen protection successively, 30 moles of 4-bromo-4 '-ethyl biphenyls, 6 moles of yellow prussiate of potash; 2.5 the mole cuprous iodide, 5 moles of potassiumiodides, 24 moles of N, N '-dimethyl-ethylenediamine; Under nitrogen protection,, finish reaction 165 ℃ of stirring reactions 48 hours, cool to room temperature, suction filtration reclaims inorganic salt; Filtrate decompression reclaims solvent sym-trimethylbenzene and N, and N '-dimethyl-ethylenediamine, residue carry out high-vacuum fractionation and obtain liquid crystal intermediates 4-cyanic acid-4 '-ethyl biphenyl, productive rate 85%; Mp73～74 ℃, 22 ℃ of clearing points ¹H 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.