CN104725270B - Method for preparing butylphenylacetonitrile - Google Patents
Method for preparing butylphenylacetonitrile Download PDFInfo
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- CN104725270B CN104725270B CN201510092151.9A CN201510092151A CN104725270B CN 104725270 B CN104725270 B CN 104725270B CN 201510092151 A CN201510092151 A CN 201510092151A CN 104725270 B CN104725270 B CN 104725270B
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- acetonitrile
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- butylcyclohexylene
- butylcyclohexyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/006—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrogenation of aromatic hydroxy compounds
Abstract
The invention discloses a method for preparing butylphenylacetonitrile, and the method is capable of preparing butylphenylacetonitrile by using p-tert-butylphenol as a raw material through catalyzing, hydrogenating, and condensation with Knoevenagel of cyanoacetic acid, and catalyzing dehydro-aromatization, wherein a small amount of ethylbenzene is added into the reaction mixture in the dehydro-aromatization catalyzing step, and meanwhile, as the technical means of introducing inert gas with a certain flow rate is adopted, the preparation method provided by the invention has industrial application value. Compared with the existing preparation method, the method provided by the invention has the advantages that the raw material is easy to get, the yield is high, the cost is low, isomers which are difficult to separate are not contained, highly toxic sodium cyanide and other highly toxic irritating ingredients are not used, the three wastes are less, the security is high and the like, so that the method provided by the invention is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of fine-chemical intermediate, particularly to a kind of intermediate of insecticidal/acaricidal agent to tert-butyl benzene
The synthetic method of acetonitrile.
Background technology
It is colourless to faint yellow to tert-butyl benzene acetonitrile, have the liquid of special fishlike smell, be synthesizing new insecticidal/acaricidal agent
The important intermediate of cyflumetofen (cyflumetofen), is also a kind of useful spice (European patent ep 0062368).
Cyflumetofen is the new acaricide of big chemical company of Japan exploitation, lists in Japan first, mainly within 2007
For preventing and treating the evil mite of fruit tree, vegetable, tea, ornamental plant etc., with existing insecticide no interactions resistance.To various plants all no medicines
Evil, fool proof to non-target organisms such as mammal, aquatile, beneficial organism, natural enemies, belong to environmentally friendly agricultural chemical (beautiful
State's patent us 2003/0208086, pesticide 2009,48(7), 474-475,478, modern 2009,8(4), 23-24).
Report to tert-butyl benzene acetonitrile synthetic route all with to tert-butyl group benzyl chloride or to tert-butyl group cylite for close
Key intermediate, is obtained through being condensed with Cyanogran., prints 2003,17(9 when such as European patent ep 0062368 and chemical industry), 43-44.
There are two methods to tert-butyl group benzyl chloride or to the synthesis of tert-butyl group cylite: 2-methyl-2-phenylpropane is in anhydrous zinc chloride and hydrogen halide
In the presence of carry out halomethylation with paraformaldehyde and react being obtained, or in the presence of p-tert-butyltoluene is through illumination or radical initiator
Free radical replace halogenation be obtained, reaction equation is as follows:
About 10% meta-isomer is produced during 2-methyl-2-phenylpropane halomethylation, very much like with required para-position product characteristicses, difficult
Removed with separating from product.Additionally, it is high-boiling components that halomethylation reaction also can produce more dimerization and poly by-product.Right
Major control halogenation depth during t-butyltoluene halogenation, but raw materials used p-tert-butyltoluene is obtained by the tert-butylation of toluene,
Same be difficult to containing about 10% that when detached meta-isomer, halogenation and subsequent cyaniding, reactivity is similar, lead to final products
Content low, need repeatedly to refine, yield is low, consume big.In addition, the intermediate of above two syntheti c route is to tert-butyl group halogenation
Benzyl has larger toxicity and zest, the Cyanogran. severe toxicity of use, and these all bring very big to production safety, labor protection etc.
Problem.
In a word, above two syntheti c routes all exist more and are difficult to separate the meta-isomer removing, these isomeries
The activity that body participates in next step reaction is similar to principal product, therefore can have influence on quality, yield and the cost of final pesticide always.
In addition the shortcomings of these routes also have that equipment corrosion is serious, the three wastes are many, poor stability, labour protection have high demands, so in the urgent need to
Low cost, the three wastes few, safe to tert-butyl benzene acetonitrile technique, particularly do not use hypertoxic Cyanogran., do not produce difficult point
From isomer to tert-butyl benzene acetonitrile technique.
Content of the invention
In order to overcome in prior art that by-product is serious, pollution is big, poor stability the shortcomings of, the invention provides a kind of right
The preparation method of tert-butyl benzene acetonitrile.
With cheap p-t-butyl phenol as raw material, through catalytic hydrogenation, vacuum distillation obtains the 4- tert-butyl group to the present invention
Ketohexamethylene, then carry out the prepared 4- tert-butylcyclohexylene acetonitrile of knoevenagel condensation and 4- t-butylcyclohexyl alkene with cyanoacetic acid
The mixture of base acetonitrile, then through catalytic dehydrogenation aromatization, add benzene second in catalytic dehydrogenation aromatization link is to reactant mixture
Alkene, cinnamic addition be catalytic dehydrogenation aromatization link add 4- tert-butylcyclohexylene acetonitrile and 4- tert-butyl group ring
The 0.2%-2.0% of hexenyl acetonitrile mixture weight, is passed through the noble gases of certain flow rate simultaneously, is obtained to tert-butyl benzene acetonitrile
Product.The synthetic route of the present invention is as follows:
Preparation method to tert-butyl benzene acetonitrile proposed by the present invention, is characterized in that with p-t-butyl phenol as raw material, warp
Selective catalytic hydrogenation is obtained 4- tbutylcyclohexanone, is easy to the feature being condensed using ketone carbonyl, carries out with cyanoacetic acid
Knoevenagel condensation generates the mixture of 4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl acetonitrile,
By catalytic dehydrogenation aromatization, add a small amount of styrene in catalytic dehydrogenation aromatization link is to reactant mixture, lead to simultaneously
Enter the noble gases of certain flow rate, be obtained to tert-butyl benzene acetonitrile.Because p-t-butyl phenol content is very high, the position of condensation is true
Fixed, reaction does not produce position isomer, and therefore products therefrom purity is very high.Although it is different each other that condensation reaction can obtain position of double bond
The 4- tert-butylcyclohexylene acetonitrile of structure and 4- t-butylcyclohexyl thiazolinyl acetonitrile, but obtain identical after dehydrogenation and aromatization
Product is to tert-butyl benzene acetonitrile.
The preparation method of the present invention avoids halomethylation reaction, the shortcoming of halogen substitution reaction, and using hypertoxic cyaniding
The shortcomings of sodium, generation difficult separation isomer, the three wastes of technique substantially reduce, and safety greatly improves, and cost is remarkably decreased.
Hydrogenation in the present invention can be carried out by known method, such as United States Patent (USP) us 6015927.
Knoevenagel condensation reaction in the present invention, is referred to Chinese Journal of Pharmaceuticals 39 phase p161- in 2008
Similar approach disclosed in 162 is carried out, and preferably carries out in the presence of ammonium acetate, piperidines, benzylamine catalyst.
Dehydrogenation and aromatization in the present invention, due to containing, in raw material, the carbon-carbon double bond that is easily hydrogenated, and raw material and
All containing the cyano group being easily hydrogenated in product, conventional reaction condition can produce more by-product, lead to product yield and contain
Amount is low to be worth so as to not have industrial applications, and the dehydrogenation and aromatization of therefore such structural compounds has no any disclosure
Document report.Result of study as applicant shows: 4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl second
The mixture of nitrile is catalyst in palladium/charcoal, and toluene, ethylbenzene, isopropylbenzene, various dimethylbenzene and its mixture are that the routine of solvent takes off
Under hydrogen aromatization conditions, can generate to tert-butyl benzene acetonitrile, but the yield of product and content are relatively low.Inventor is through excessive
Amount experimental exploring, reaction is catalyst from 5% to 10% palladium/charcoal, and the solvent of reaction uses toluene, ethylbenzene, isopropylbenzene, dimethylbenzene
And its mixture；Under the conditions of catalytic dehydrogenation, employ and add a small amount of styrene in reactant mixture, be passed through a constant current simultaneously
The noble gases technological means such as such as nitrogen or argon of speed, the styrene due to adding can be anti-with the hydrogen that dehydrogenation produces rapidly
Ethylbenzene should be generated, it is to avoid the hydrogen of effusion reaction system and carbon-carbon double bond or cyano group do not occur addition to lead to by-product in time
Formed, the suitable solvent of the ethylbenzene of generation and precisely dehydrogenation reaction.Therefore, it is possible to realize greatly improving products therefrom to tertiary fourth
The purity of base benzene acetonitrile and the purpose of yield, make the present invention have industrial value.
The present invention is raw material by p-t-butyl phenol, through catalytic hydrogenation, knoevenagel condensation, dehydroaromatizationof three step
Reaction is obtained to tert-butyl benzene acetonitrile.With existing halomethylation, cyaniding, or the technique of free radical halo, cyaniding compares, and has
Separate isomer, do not use that hypertoxic Cyanogran. and high toxicity and zest technique, quality are good, low cost, the three wastes are few, peace without difficult
The advantages of property is high entirely, has good industrial prospect.
Specific embodiment
Used by following instance, chemical raw material, solvent etc. are technical grade product, without being further purified.Content is with gas phase color
Spectrum normalization method measures.
Embodiment 1
The synthesis of 4- tbutylcyclohexanone
Add Borax 0.5g, water 3.5g and 5% Pd/carbon catalyst 3g in autoclave, after mix homogeneously, add to the tert-butyl group
Phenol 120g(0.8mol) and 150ml hexahydrotoluene, air in kettle is drained, logical hydrogen, to about 5 atmospheric pressure, is heated with stirring to
100 DEG C are reacted to no longer inhaling hydrogen, about need 5h.Cooling, filters off catalyst, normal pressure desolventizing, vacuum distillation obtains product, receives
Rate 88.5%, wherein tbutylcyclohexanone containing 4- 96.4%, the tert. butyl cyclohexanol of 4- containing cis-trans 1.7%.
Embodiment 2
The synthesis of 4- tbutylcyclohexanone
Add p-t-butyl phenol 120g(0.8mol in autoclave), 10% Pd/carbon catalyst 1.5g and 150ml n-butyl alcohol,
Air in kettle is drained, logical hydrogen, to about 3 atmospheric pressure, is heated with stirring to 90 DEG C and reacts to no longer inhaling hydrogen, about need 12h.Cold
But, catalyst, normal pressure desolventizing are filtered off, vacuum distillation obtains product, yield 76.9%, wherein tbutylcyclohexanone containing 4-
95.2%, 4- containing cis-trans tert. butyl cyclohexanol 2.2%.
Embodiment 3
4- tbutylcyclohexanone is condensed with the knoevenagel of cyanoacetic acid
Equipped with product 16.0 g, the benzene 140ml that add embodiment 1 gained in the four-hole bottle of stirring, condensing tube and water knockout drum
With ammonium acetate 3.9g (0.05mol), it is heated with stirring to 90 DEG C, is dividedly in some parts cyanoacetic acid 8.5g (0.1mol), flow back azeotropic dehydration,
Dehydration terminates Distillation recovery benzene, obtains intermediate 4- tert-butylcyclohexylene cyanoacetic acid.Add acetic acid 30ml wiring solution-forming while hot.
The mixed liquor of another acetic acid 50ml and piperidines 20ml composition is heated to 180 DEG C, is uniformly added into gained 4- tert-butyl group Asia hexamethylene
The acetum of base cyanoacetic acid, controls carbon dioxide uniformly to release.After carbon dioxide is released and slowed down, continue anti-under tiny structure
Should.Decarboxylation terminates, and rectification under vacuum obtains the mixture of 4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl acetonitrile, receives
The content of rate 90.3%, wherein 4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl acetonitrile be respectively 79.3% and
19.9%, both total contents 99.2%.
Embodiment 4
4- tbutylcyclohexanone is condensed with the knoevenagel of cyanoacetic acid
Equipped with product 16.0 g, the cyanoacetic acid that add embodiment 2 gained in the four-hole bottle of stirring, condensing tube and water knockout drum
12.8g (0.15mol), benzylamine 2.7g (0.025mol), enanthic acid 3.3g (0.025 mol) and toluene 160ml, are stirred at reflux azeotropic
It is dehydrated 24 h, is cooled to room temperature, reactant liquor is washed with 2mol/l sodium hydroxide 60ml, water 60ml and saturated aqueous common salt 60ml successively,
Anhydrous magnesium sulfate is dried, and filters, and filtrate is evaporated off toluene, obtains 4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl second
The mixture of nitrile, yield 94%, the wherein content difference of 4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl acetonitrile
For 56.5% and 42.3%, both total contents 98.8%.
Embodiment 5
4- tert-butylcyclohexylene acetonitrile and the catalytic dehydrogenation aromatization of 4- t-butylcyclohexyl thiazolinyl acetonitrile mixture
4- tert-butylcyclohexylene acetonitrile and the mixture of 4- t-butylcyclohexyl thiazolinyl acetonitrile that Example 3 is obtained
17.7g, styrene 35mg, ethylbenzene 80ml add in four-hole bottle, and logical argon 5min adds 5% Pd/carbon catalyst 5.0g, under normal pressure
Back flow reaction 24h, is slowly introducing argon simultaneously.After dehydrogenation terminates, cooling, filter catalyst, vacuum distillation removes solvent, remaining
Thing is recrystallized to give to tert-butyl benzene acetonitrile, yield 93%, content 98.9%.
Embodiment 6
4- tert-butylcyclohexylene acetonitrile and the catalytic dehydrogenation aromatization of 4- t-butylcyclohexyl thiazolinyl acetonitrile mixture
4- tert-butylcyclohexylene acetonitrile and the mixture of 4- t-butylcyclohexyl thiazolinyl acetonitrile that Example 4 is obtained
17.7g, styrene 350mg, toluene 80ml add in four-hole bottle, and logical nitrogen 5min adds 10% Pd/carbon catalyst 6.0g, normal pressure
Lower back flow reaction 24h, is slowly introducing nitrogen simultaneously.After dehydrogenation terminates, cooling, filter catalyst, vacuum distillation removes solvent, residual
Excess is recrystallized to give to tert-butyl benzene acetonitrile, yield 95%, content 98.6%.
Comparative example 1
4- tert-butylcyclohexylene acetonitrile and the catalytic dehydrogenation aromatization of 4- t-butylcyclohexyl thiazolinyl acetonitrile mixture
4- tert-butylcyclohexylene acetonitrile and the mixture of 4- t-butylcyclohexyl thiazolinyl acetonitrile that Example 4 is obtained
17.7g (0.1mol), mixed xylenes 80ml, add 10% Pd/carbon catalyst 6.0g, back flow reaction 24h under normal pressure.Dehydrogenation is tied
Shu Hou, cooling, filter catalyst, vacuum distillation removes solvent, residue is recrystallized to give to tert-butyl benzene acetonitrile, yield 68%,
Content 45.3%.
The industry it is to be understood by the skilled artisans that the present invention is not restricted to the described embodiments, above-described embodiment and explanation
Described in book simply to illustrate that the principle of the present invention.Without departing from the spirit and scope of the present invention, the present invention goes back
Have various changes and modifications, these both fall within the scope of protection of present invention.
Claims (1)
1. a kind of preparation method to tert-butyl benzene acetonitrile, is carried out successively in the steps below: with p-t-butyl phenol as raw material, warp
Catalytic hydrogenation, vacuum distillation obtain 4- tbutylcyclohexanone；4- tbutylcyclohexanone and cyanoacetic acid carry out knoevenagel condensation
Prepared 4- tert-butylcyclohexylene acetonitrile and the mixture of 4- t-butylcyclohexyl thiazolinyl acetonitrile, knoevenagel condensation reaction exists
Carry out in the presence of ammonium acetate, piperidines, benzylamine catalyst；4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl acetonitrile
Mixture be obtained to tert-butyl benzene acetonitrile product through catalytic dehydrogenation aromatization again, catalytic dehydrogenation aromatization reaction is 5% to 10%
Carry out under palladium/charcoal catalytic condition, the solvent of reaction uses toluene, ethylbenzene, isopropylbenzene, dimethylbenzene and its mixture, de- in catalysis
Hydrogen aromatisation link adds styrene in reactant mixture, and cinnamic addition adds for catalytic dehydrogenation aromatization link
The 0.2%-2.0% of the mixture weight of 4- tert-butylcyclohexylene acetonitrile and 4- t-butylcyclohexyl thiazolinyl acetonitrile, is passed through one simultaneously
The noble gases of constant current speed, the noble gases being passed through are nitrogen or helium.
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| NL8101739A (en) * | 1981-04-08 | 1982-11-01 | Naarden International Nv | PERFUME COMPOSITIONS AND PERFUMED ARTICLES CONTAINING ALKYL SUBSTITUTED BENZYLCYANIDES AS PERFUME. |
| DE19727712A1 (en) * | 1997-06-30 | 1999-01-07 | Bayer Ag | Process for the preparation of cyclohexanones by hydrogenation of the corresponding phenols (left) |
| CN102336686A (en) * | 2010-07-20 | 2012-02-01 | 中国科学院上海药物研究所 | Preparation method of 2-(7-methoxy-1-naphthyl) acetonitrile |
| EP2607344A1 (en) * | 2011-12-24 | 2013-06-26 | Allessa Chemie GmbH | Method for producing cyclic ketones |
| CN104262197A (en) * | 2014-08-28 | 2015-01-07 | 太仓运通生物化工有限公司 | Synthesis method of 1-cyclohexenylacetonitrile |
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