CN106278837A - The Preparation Method And Their Intermediate of o-trifluoromethyl-4-halogenated benzaldehyde - Google Patents
The Preparation Method And Their Intermediate of o-trifluoromethyl-4-halogenated benzaldehyde Download PDFInfo
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- CN106278837A CN106278837A CN201510284383.4A CN201510284383A CN106278837A CN 106278837 A CN106278837 A CN 106278837A CN 201510284383 A CN201510284383 A CN 201510284383A CN 106278837 A CN106278837 A CN 106278837A
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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
- C07C45/42—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis
- C07C45/43—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis of >CX2 groups, X being halogen
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- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/12—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
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- C07C25/13—Monocyclic aromatic halogenated hydrocarbons containing fluorine
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Abstract
The invention discloses the Preparation Method And Their Intermediate of a kind of o-trifluoromethyl-4-halogenated benzaldehyde.The method includes method one: under condition of no solvent, and under the catalysis of acid, be hydrolyzed reaction by o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2 and water, prepares o-trifluoromethyl-4-halogenated benzaldehyde as shown in Equation 3,；Described acid is C1～C4The saturated unary fatty acid of straight chain and the mixture of inorganic acid or inorganic acid；Described inorganic acid is sulphuric acid and/or phosphoric acid；The temperature of described hydrolysis is 70 DEG C～130 DEG C；Method two: in water, under lewis acidic catalysis, be hydrolyzed reaction by o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2 and water；The temperature of described hydrolysis is 90 DEG C～100 DEG C.The preparation method reaction raw materials of the present invention is easy to get, simple to operate, low cost, and the three wastes are few, environmentally friendly, and yield and purity are high, it is adaptable to industrialized production.
Description
Technical field
The present invention relates to the Preparation Method And Their Intermediate of a kind of o-trifluoromethyl-4-halogenated benzaldehyde.
Background technology
O-trifluoromethyl-4-halogenated benzaldehyde series products is as a kind of important fine-chemical intermediate, extensively
It is applied in pesticide and medical product, becomes the focus product in fine-chemical intermediate field.China is fluorinated
Work aboundresources, but high-end, high in technological content product is few, and therefore state planted agent adds on this basis
Fast trifluoromethyl benzene-type products derivant synthetic technology research and development, need badly and carry out product up-gradation and promotion
Industry optimzing, improves fluorination work international competitiveness.
O-trifluoromethyl-4-halogenated benzaldehyde is synthesizing new medicine and the important intermediate of pesticide.The most adjacent
Trifluoromethyl-4-halogenated benzaldehyde generally has following several routes to prepare:
1, WO2013149997 discloses with 2-trifluoromethyl-4-bromo-iodobenzene as raw material, at oxolane
In exchange with isopropylmagnesium chloride Grignard reagent at-15 DEG C after react with N,N-dimethylformamide again and obtain
2-trifluoromethyl-4-bromobenzaldehyde, yield 68%.And 2-trifluoromethyl-4-bromo-iodobenzene is with a bromine trifluoro
Toluene is raw material through nitrification, reduction, and diazotising obtains, and reaction raw materials is difficult to obtain, its preparation method
In high to producing equipment requirements, reactions steps is long, expensive starting materials, and yield is low, pollutes too big, is unfavorable for
Industrialized great production.
2, WO2006/44454 discloses with 2-trifluoromethyl-4-chlorobenzonitrile as raw material, at formic acid and
In water, under the effect of alumel, 100 DEG C of reactions prepare 2-trifluoromethyl-4-chlorobenzaldehyde, yield
87%.2-trifluoromethyl-4-chlorobenzonitrile is to react with cyanide with 2-trifluoromethyl-4-chloroiodobenzone for raw material
Prepare.And cyanide is hypertoxic, there is potential safety hazard, therefore, the reaction raw materials of the method is difficult to obtain,
It is unfavorable for industrialized great production.
3、Tetrahedron,2005,vol.61,27,p6590-6595；Journal of Materials
Chemistry,2011,vol.21,p9523-9531；Journal of Organic Chemistry,2013,
Vol.78, p11680-11690 etc. disclose with 2, and 5-bis-5 bromine benzotrifluoride is raw material, in oxolane or second
In ether ,-78 DEG C of elder generations prepare with DMF reaction with n-BuLi effect again, yield 40-69%.
The method is the highest to equipment requirements, and cost is high, and reaction raw materials is difficult to obtain, and is unfavorable for the big life of industrialization
Produce.
4, Tetrahedron Letters, 2013, vol.54, p6053 6056 disclose with a fluoride trifluoro toluene
For raw material, in oxolane ,-78 DEG C of elder generations react with DMF with n-BuLi effect again
Prepare.The method is the highest to equipment requirements, operation complexity, and cost is high, is unfavorable for industrialized great production.
5, US2010222345 discloses with 2-trifluoromethyl-4-bromine dibromomethylbenzene as raw material, at tetrahydrochysene furan
Muttering, react with pin acid silver in ethanol, reaction temperature is 60 DEG C.The method faces raw material equally and is difficult to obtain,
The problems such as cost is high, and operation is complicated, are unfavorable for industrialized great production.
, for technological process and cost, all there is raw material and be difficult to obtain in the most several preparation methoies, right
Equipment requirements is high, and operation complexity, relatively costly, the three wastes are many, and yield is low and is not suitable for the big life of industrialization
The problems such as product.Therefore, this area needs the preparation method of a kind of new o-trifluoromethyl-4-halogenated benzaldehyde badly
And intermediate, to solve above-mentioned technical barrier.
Summary of the invention
The technical problem to be solved is to overcome existing o-trifluoromethyl-4-halogeno-benzene first
Present in the preparation method of aldehyde and intermediate thereof, raw material is difficult to obtain, high to equipment requirements, operation complexity,
Relatively costly, the three wastes are many, and yield is low and is not suitable for the technical barriers such as industrialized great production, and provides
A kind of Preparation Method And Their Intermediate of o-trifluoromethyl-4-halogenated benzaldehyde.The preparation method of the present invention is anti-
Answering raw material to be easy to get, simple to operate, low cost, the three wastes are few, environmentally friendly, the target compound prepared
And intermediate purity and yield and purity are high, it is more suitable for industrialized production.
The present invention mainly solves above-mentioned technical barrier by the following technical programs.
The invention provides the preparation method of a kind of o-trifluoromethyl-4-halogenated benzaldehyde, it includes following step
Rapid:
Method one: under condition of no solvent, under the catalysis of acid, by o-trifluoromethyl-4-as shown in Equation 2
Halo dichlorotoleune and water carry out hydrolysis as follows, prepare o-trifluoromethyl as shown in Equation 3
-4-halogenated benzaldehyde,；Described acid is C1～C4The saturated unary fatty acid of straight chain and inorganic acid
Mixture or inorganic acid；Described inorganic acid is sulphuric acid and/or phosphoric acid；Described hydrolysis
Temperature be 70 DEG C～130 DEG C；
Method two: in water, under lewis acidic catalysis, by o-trifluoromethyl-4-as shown in Equation 2
Halo dichlorotoleune and water carry out hydrolysis as follows, prepare o-trifluoromethyl as shown in Equation 3
-4-halogenated benzaldehyde,；The temperature of described hydrolysis is 90 DEG C～100 DEG C；
Wherein, in compound 2 or compound 3, X is Br or I.
In method one, the temperature of described hydrolysis is preferably 80 DEG C～120 DEG C, is more preferably 90 DEG C
～100 DEG C.
In method one, described C1～C4The saturated unary fatty acid of straight chain can be that this area is conventional
C1～C4The saturated unary fatty acid of straight chain, preferably formic acid, acetic acid, propanoic acid and butanoic acid one or
Multiple, it is more preferably acetic acid.Described C1～C4The consumption of the saturated unary fatty acid of straight chain can be ability
The consumption that this type of reaction of territory is conventional, it is preferred that itself and o-trifluoromethyl-4-halo dichloro as shown in Equation 2
The mol ratio of toluene is 2:1～20:1, is more preferably 4:1～10:1, is most preferably 5:1～8:1.
In method one, described sulphuric acid and described phosphoric acid are the most commercially.Wherein said sulphuric acid
Preferably concentrated sulphuric acid or oleum.Described concentrated sulphuric acid is preferably meant that mass fraction is 85%～98%
Aqueous sulfuric acid.Described phosphoric acid preferably mass fraction is the phosphate aqueous solution of more than 85%.On
State each percentage ratio (%) and each mean that the quality of each inorganic acid accounts for the percentage of inorganic acid aqueous solution gross mass
Ratio.The consumption of described inorganic acid can be the consumption that this type of reaction of this area is conventional, it is preferred that its with
The mol ratio of o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2 is 2:1～20:1, is more preferably
4:1～10:1, is most preferably 5:1～8:1.Described inorganic acid participates in the most in form of an aqueous solutions
In reaction.
In method one, the consumption of described water can be the consumption that this type of reaction of this area is conventional, it is preferred that
It is 0.1:1～10:1 with the mol ratio of o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2；More preferably
Ground is 0.1:1～5:1, is more preferably 0.1:1～1:1 (such as 0.5:1).When described inorganic acid is with water-soluble
When the form of liquid participates in reaction, if the amount of water therein be enough to the o-trifluoromethyl made as shown in Equation 2
-4-halo dichlorotoleune is hydrolyzed reaction, now, without additionally adding water in reaction system.
In method two, described lewis acid can be the lewis acid that this area is conventional, preferably chlorination
One or more in zinc, iron chloride and zinc sulfate.Described lewis acid consumption can be this area this type of
The consumption that reaction is conventional, it is preferred that itself and o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2
Mol ratio is 1:1～20:1, is more preferably 4:1～10:1, is most preferably 2:1～8:1.The consumption of described water
Can being the conventional consumption in this area, carrying out as long as not affecting reaction, it is preferred that described water and such as
The volume mass of the o-trifluoromethyl-4-halo dichlorotoleune shown in formula 2 is than preferably
1mL/g～20mL/g, is more preferably 5mL/g～10mL/g.
In method one or method two, the process of described hydrolysis can be according to this area traditional test methods
(such as TLC, GC, HPLC or NMR) is monitored, and preferably uses gas chromatogram to detect,
Typically < make when 0.5% with the content (GC%) of o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2
Terminal for reaction.The time of described hydrolysis is preferably 1～30 hour, is more preferably 10～20
Hour.
In method one or method two, after described hydrolysis terminates, also can further include post processing
Operation.The method of described post processing and condition can be method and the condition of this type of reaction routine of this area,
The preferred following method of the present invention and condition: the reactant liquor after being terminated by hydrolysis, be cooled to room temperature, take out
Filter, filtrate extracts with organic solvent, obtains organic layer, and organic layer washes with water or regulates pH value extremely with alkali
6.5～7.5 (wherein, described alkali can be the alkali that this area is conventional, as long as not with chemical combination as shown in Equation 3
Thing reacts, it is possible to after regulation extraction, the pH value of organic layer is to 6.5～7.5), remove organic
Solvent, distillation, collect the fraction of 90～95 DEG C/-0.095MPa,.Having used by described extraction
Machine solvent can be the organic solvent that this area extraction is conventional, preferably halogenated hydrocarbon solvent, such as dichloro
Methane.The described method removing organic solvent can be the method that this area is conventional, steaming of preferably reducing pressure
Evaporate.The operation of described distillation can be the operation that this area is conventional, distillation of preferably reducing pressure.
The preparation method of described o-trifluoromethyl-4-halogenated benzaldehyde, it also can further include following step
Rapid: in acetic acid, under the catalysis of sulphuric acid, by o-trifluoromethyl dichlorotoleune as shown in Equation 1 and halo
Reagent carries out selectivity halogenating reaction as follows, prepares o-trifluoromethyl-4-halo as shown in Equation 2
Dichlorotoleune,；Described halogenating agent is DBDMH or diiodo-glycolylurea；
Wherein, in compound 2, X is Br or I.
Described selectivity halogenating reaction is preferably comprised the following step: after being mixed with sulphuric acid by acetic acid, then
Mix with o-trifluoromethyl dichlorotoleune as shown in Equation 1, under conditions of 0～90 DEG C, add halo examination
Agent, carries out described selectivity halogenating reaction.The described temperature adding halogenating agent is preferably
10～50 DEG C, it is more preferably 25～40 DEG C.
The consumption of described halogenating agent can be the consumption that this type of reaction of this area is conventional, it is preferred that its with
The mol ratio of o-trifluoromethyl dichlorotoleune as shown in Equation 1 is 0.5:1～3:1；It is more preferably
0.5:1～1.5:1.
The consumption of described acetic acid can be the consumption that this type of reaction of this area is conventional, it is preferred that its with such as formula
The mol ratio of the o-trifluoromethyl dichlorotoleune shown in 1 is 2:1～20:1, is more preferably 2:1～8:1, most preferably
Ground is 2:1～6:1.
Described sulphuric acid is generally the most commercially, preferably concentrated sulphuric acid or oleum.Described dense sulfur
Acid is preferably meant that the aqueous sulfuric acid that mass fraction is 85%～98%.The consumption of described sulphuric acid can be
The consumption that this type of reaction of this area is conventional, it is preferred that itself and o-trifluoromethyl dichloromethane as shown in Equation 1
The mol ratio of benzene is 2:1～20:1, is more preferably 2:1～8:1, is most preferably 2:1～6:1.
The temperature of described selectivity halogenating reaction can be the temperature that this type of reaction of this area is conventional, preferably
It is 25～40 DEG C, is more preferably 35 DEG C.The process of described selectivity halogenating reaction can be normal according to this area
Rule method of testing (such as TLC, GC, HPLC or NMR) are monitored, and preferably use gas phase color
Spectrum detects, typically with the content (GC%) < 0.5% of o-trifluoromethyl dichlorotoleune as shown in Equation 1
The terminal of Shi Zuowei reaction.The time of described selectivity halogenating reaction is preferably 2～40 hours, more
It it is 4～16 hours goodly.
After described selectivity halogenating reaction terminates, also can further include the operation of post processing.Described
The method of post processing and condition can be the conventional method of this type of reaction of this area and condition, the present invention preferably under
Row method and condition: the reactant liquor after selectivity halogenating reaction is terminated, ice-water bath is cooled to-5 DEG C～0 DEG C,
Adding water, extract with organic solvent, obtain organic layer, organic layer washes with water or regulates pH value extremely with alkali
6.5～7.5 (wherein, described alkali can be the alkali that this area is conventional, as long as not with chemical combination as shown in Equation 2
Thing reacts, it is possible to after regulation extraction, the pH value of organic layer is to 6.5～7.5), remove organic
Solvent,.The described amount adding water can be this area conventional amount used.The described operation adding water
After end, after being preferably stirred at room temperature 0.5～1 hour, then extract with organic solvent.Described extraction
Organic solvent used can be the organic solvent that this area extraction is conventional, preferably halogenated hydrocarbon solvent,
Such as dichloromethane.The consumption of described organic solvent can be this area conventional amount used.Described removing has
The method of machine solvent can be the method that this area is conventional, distillation of preferably reducing pressure.
Present invention also offers a kind of o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2:
Wherein, in compound 2, X is Br or I.
Present invention also offers the preparation method of a kind of o-trifluoromethyl-4-halo dichlorotoleune, under it comprises
Row step: in acetic acid, under the catalysis of sulphuric acid, by o-trifluoromethyl dichlorotoleune as shown in Equation 1 with
Halogenating agent carries out selectivity halogenating reaction as follows, prepares described adjacent trifluoro as shown in Equation 2
Methyl-4-halo dichlorotoleune,；Described halogenating agent is two chlordantoins, DBDMH or diiodo-
Glycolylurea；
Wherein, in compound 2, X is Cl, Br or I.
The condition of the method for described selectivity halogenating reaction is all the same described.
In the present invention, room temperature refers to 10～30 DEG C.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can combination in any, obtain this
Invent each preferred embodiments.
Agents useful for same of the present invention and raw material are the most commercially.
The most progressive effect of the present invention is:
The preparation method reaction raw materials of the present invention is easy to get, simple to operate, low cost, and the three wastes are few, to environment
Close friend, prepared target compound and intermediate purity and yield thereof and purity are high, are more suitable for industry metaplasia
Produce.
Detailed description of the invention
Further illustrate the present invention below by the mode of embodiment, but the most therefore limit the present invention to
Among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, according to often
Rule method and condition, or select according to catalogue.
In following embodiment, room temperature refers to 10～30 DEG C.Concentrated sulphuric acid refers to the dense sulfur that mass fraction is 98%
Acid.Reflux temperature, as do not made specified otherwise, generally refers to the reflux temperature of water, between i.e. 90～100 DEG C.
Embodiment 1
250mL there-necked flask adds 18.7mL concentrated sulphuric acid (0.34mol) and 15mL acetic acid (0.26mol)
Stirring is cooled to room temperature, adds 15g (0.066mol) o-trifluoromethyl dichlorotoleune and 11.24g (0.039mol)
DBDMH, 35 DEG C of stirring 6hr.Ice-water bath cooling dropping 100mL water, is stirred at room temperature 0.5hr, adds
Entering dichloromethane 100mL extraction, organic facies is washed to neutrality, and steaming vibrating dichloromethane obtains 19g neighbour's trifluoro
Methyl-4-bromine dichlorotoleune.Yield is 94%, and GC purity is 94%.1HNMR(CDCl3400Mz).
7.62 (1H, s), 7.44 (1H, d, J=8.3Hz), 7.1 (1H, d, J=8.3Hz), 6.7 (1H, s).
Embodiment 2
250mL there-necked flask adds 18.7mL concentrated sulphuric acid (0.34mol) and 15mL acetic acid (0.26mol)
Stirring is cooled to room temperature, adds 15g (0.066mol) o-trifluoromethyl dichlorotoleune and 7.68g (0.039mol)
Two chlordantoins, 35 DEG C of stirring 6hr.Ice-water bath cooling dropping 100mL water, is stirred at room temperature 0.5hr, adds
Entering dichloromethane 100mL extraction, organic facies is washed to neutrality, 15.3g neighbour's trifluoro of steaming vibrating dichloromethane
Methyl-4-chlorine dichlorotoleune.Yield 89%, GC purity is 97%.1HNMR(CDCl3400Mz).
7.45 (1H, s), 7.28 (1H, d, J=8.1Hz), 7.11 (1H, d, J=8.1Hz), 6.7 (1H, s).
Embodiment 3
To with stirring, condensing reflux reaction bulb in, put into 50mL concentrated sulphuric acid (0.92mol), 40mL
Acetic acid (0.70mol), 23g (0.10mol) o-trifluoromethyl dichlorotoleune and 23.6g (0.12mol)
Two chlordantoins, 35 DEG C of stirring 6hr.Ice-water bath cooling dropping 200mL water, is stirred at room temperature 1hr, adds
Dichloromethane 200mL extracts, and organic facies is washed to neutrality, and steaming vibrating dichloromethane obtains 15.3g neighbour's fluoroform
Base-4-chlorine dichlorotoleune.Yield 89%, GC purity is 97%.
Embodiment 4
There-necked flask adds 18.7mL concentrated sulphuric acid and the stirring of 15mL acetic acid is cooled to room temperature, add 15g
(0.066mol) o-trifluoromethyl dichlorotoleune and 11.24g (0.039mol) DBDMH, 25 DEG C are stirred
Mix 16hr.Ice-water bath cooling dropping 100mL water, is stirred at room temperature 0.5hr, adds dichloromethane 100mL
Extraction, organic facies is washed to neutrality, and steaming vibrating dichloromethane obtains 19g o-trifluoromethyl-4-bromine dichlorotoleune.
Yield is 94%, and GC purity is 95%.
Embodiment 5
150mL there-necked flask adds 18mL concentrated sulphuric acid (0.33mol) and 15mL acetic acid (0.26mol)
Stirring is cooled to room temperature, adds 15g (0.066mol) o-trifluoromethyl dichlorotoleune, 6.2g (0.039mol)
Diiodo-glycolylurea, 35 DEG C of stirring 6hr.Ice-water bath cooling dropping 100mL water, is stirred at room temperature 0.5hr, adds
Entering dichloromethane 100mL extraction, organic facies is washed to neutrality, and steaming vibrating dichloromethane obtains 18.8g neighbour's trifluoro
Methyl-4-iodine dichlorotoleune.Yield is 81%, and GC purity is 93%.1HNMR(CDCl3400Mz).
7.89 (1H, s), 7.42 (1H, d, J=8.1Hz), 7.19 (1H, d, J=8.1Hz), 6.7 (1H, s).
Comparative example 1
To with stirring, condensing reflux reaction bulb in, put into 50mL concentrated sulphuric acid (0.92mol), 40mL
Acetic acid (0.70mol), 23g (0.10mol) o-trifluoromethyl dichlorotoleune, stirring is warming up to 35 DEG C,
Being passed through chlorine (amount of chlorine ensures at more than 0.12mol), reaction is carried out 6 hours, by gas phase color
Analysis of spectrum, and o-trifluoromethyl dichlorotoleune < 1%, o-trifluoromethyl-4-chlorine dichlorotoleune content 27%.
Comparative example 2
To with stirring, condensing reflux reaction bulb in, put into 50mL concentrated sulphuric acid (0.92mol), 40mL
Acetic acid (0.70mol), 23g (0.10mol) o-trifluoromethyl dichlorotoleune, stirring is warming up to 35 DEG C,
Adding 19.2g (0.12mol) bromine, reaction is carried out 6 hours, by gas chromatographic analysis, and adjacent trifluoro
Methyl dichloro toluene 35%, o-trifluoromethyl-4-bromine dichlorotoleune content 36%.
Comparative example 3
To with stirring, condensing reflux reaction bulb in, put into 50mL concentrated sulphuric acid (0.92mol), 40mL
Acetic acid (0.70mol), 23g (0.10mol) o-trifluoromethyl dichlorotoleune, 16g (0.12mol) NCS,
35 DEG C of stirring 6hr, by gas chromatographic analysis, o-trifluoromethyl dichlorotoleune 25%, o-trifluoromethyl
-4-chlorine dichlorotoleune content 20%.
Comparative example 4
To with stirring, condensing reflux reaction bulb in, put into 50mL concentrated sulphuric acid (0.92mol), 40mL
Acetic acid (0.70mol), 23g (0.10mol) o-trifluoromethyl dichlorotoleune, 21.2 grams (0.12mol)
NBS, 35 DEG C of stirring 6hr, by gas chromatographic analysis, o-trifluoromethyl dichlorotoleune 30%, neighbour three
Methyl fluoride-4-bromine dichlorotoleune content 31%.
Comparative example 5
150mL there-necked flask adds 18mL concentrated sulphuric acid (0.33mol) and 15mL acetic acid (0.26mol)
Stirring is cooled to room temperature, adds 15g (0.066mol) o-trifluoromethyl dichlorotoleune, 8.38g (0.033mol)
Iodine, 2.18g (0.011mol) sodium iodate 35 DEG C stirring 6hr.By gas chromatographic analysis, adjacent fluoroform
Base dichlorotoleune 81%, o-trifluoromethyl-4-iodine dichlorotoleune content 7%.
Comparative example 6
150mL there-necked flask adds 18mL concentrated sulphuric acid (0.33mol) and 15mL acetic acid (0.26mol)
Stirring is cooled to room temperature, adds 15g (0.066mol) o-trifluoromethyl dichlorotoleune and 8.38g (0.033mol)
Iodine, 2.35g (0.011mol) potassium iodate 35 DEG C stirring 6hr.By gas chromatographic analysis, adjacent fluoroform
Base dichlorotoleune 78%, o-trifluoromethyl-4-iodine dichlorotoleune content 8%.
Comparative example 7
To with stirring, condensing reflux reaction bulb in, put into 40mL acetic acid, 50mL mass fraction
It is the phosphoric acid of 85%, 23g (0.10mol) o-trifluoromethyl dichlorotoleune, 17.2g (0.06mol) two
Bromine glycolylurea, 35 DEG C are stirred 6 hours, by gas chromatographic analysis, o-trifluoromethyl dichlorotoleune 45%,
O-trifluoromethyl-4-bromine dichlorotoleune content 17%.
Comparative example 8
To with stirring, condensing reflux reaction bulb in, put into 40mL trifluoroacetic acid, the dense sulfur of 50mL
Acid, 23g (0.10mol) o-trifluoromethyl dichlorotoleune, 17.2g (0.06mol) DBDMH, 35 DEG C
Stir 6 hours, by gas chromatographic analysis, o-trifluoromethyl dichlorotoleune 1 < %, o-trifluoromethyl-4-
Bromine dichlorotoleune content 60%.
Comparative example 9
To with stirring, condensing reflux reaction bulb in, put into 40mL propanoic acid, 50mL concentrated sulphuric acid,
23g (0.10mol) o-trifluoromethyl dichlorotoleune, 17.2g (0.06mol) DBDMH, 35 DEG C are stirred
Mix 6 hours, by gas chromatographic analysis, o-trifluoromethyl dichlorotoleune 7%, o-trifluoromethyl-4-bromine
Dichlorotoleune content 55%.
Comparative example 10
To with stirring, condensing reflux reaction bulb in, put into 40mL butanoic acid, 50mL concentrated sulphuric acid,
23g (0.10mol) o-trifluoromethyl dichlorotoleune, 17.2g (0.06mol) DBDMH, 35 DEG C are stirred
Mix 6 hours, by gas chromatographic analysis, o-trifluoromethyl dichlorotoleune 20%, o-trifluoromethyl-4-
Bromine dichlorotoleune content 40%.
Embodiment 6
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g (0.15mol) concentrated sulphuric acid, 20g
Acetic acid (0.27mol) mixes, and 95 DEG C are stirred 16 hours, is cooled to room temperature and adds 100mL water, 100mL
Dichloromethane extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 14.2g neighbour's trifluoro
Methyl-4-bromobenzaldehyde.Yield 86%, GC purity is 98%.1HNMR(CDCl3400Mz).
10.24 (1H, s), 8.00 (1H, s), 7.94 (1H, d, J=8Hz), 7.86 (1H, d, J=8Hz).
Embodiment 7
20g (0.056mol) o-trifluoromethyl-4-iodine dichlorotoleune, 15g (0.15mol) concentrated sulphuric acid, 20g
Acetic acid (0.27mol) mixes, and 95 DEG C are stirred 16 hours, is cooled to room temperature and adds 100mL water, 100mL
Dichloromethane extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 12g neighbour's fluoroform
Base-4-benzaldehyde iodine.Yield 71%, GC purity is 95%,1HNMR(CDCl3400Mz).10.21(1H,
S), 8.52 (1H, s), 7.61 (1H, d, J=8.4Hz), 7.71 (1H, d, J=8.4Hz).
Embodiment 8
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g (0.145mol) mass fraction
Being the aqueous sulfuric acid of 95%, 95 DEG C are stirred 16 hours, are cooled to room temperature and add 100mL water, 100mL
Dichloromethane extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 14.2g neighbour's trifluoro
Methyl-4-bromobenzaldehyde.Yield 86%, GC purity is 98%.
Embodiment 9
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g concentrated sulphuric acid, 20g formic acid mixes,
95 DEG C are stirred 16 hours.Being cooled to room temperature and add 100mL water, 100mL dichloromethane extracts, organic
Being washed to neutrality mutually, boil off solvent, decompression distillation obtains 13.1g o-trifluoromethyl-4-chlorobenzaldehyde.Receive
Rate 80%, GC purity is 93%.
Embodiment 10
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g concentrated sulphuric acid, 20g propanoic acid mixes,
95 DEG C are stirred 16 hours, are cooled to room temperature and add 100mL water, and 100mL dichloromethane extracts, organic
Being washed to neutrality mutually, boil off solvent, decompression distillation obtains 14g o-trifluoromethyl-4-bromobenzaldehyde.Yield
85%, GC purity is 98%.
Embodiment 11
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g concentrated sulphuric acid, 20g butanoic acid mixes,
95 DEG C are stirred 16 hours, by gas chromatographic analysis, o-trifluoromethyl-4-bromine dichlorotoleune 15%, neighbour
Trifluoromethyl-4-bromobenzaldehyde 70%.Being cooled to room temperature and add 100mL water, 100mL dichloromethane extracts
Taking, organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 9.6g o-trifluoromethyl-4-chlorobenzene
Formaldehyde.Yield 59%, GC purity is 82%.
Embodiment 12
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is the phosphorus of 85%
Aqueous acid, 20g acetic acid mixes, and 95 DEG C are stirred 16 hours, by gas chromatographic analysis, adjacent fluoroform
Base-4-bromine dichlorotoleune 20%, o-trifluoromethyl-4-bromobenzaldehyde 73%.It is cooled to room temperature and adds 100mL
Water, 100mL dichloromethane extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains
11.7g o-trifluoromethyl-4-chlorobenzaldehyde.Yield 71%, GC purity is 92%.
Embodiment 13
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is the phosphorus of 85%
Aqueous acid mixes, and 95 DEG C are stirred 16 hours, by gas chromatographic analysis, o-trifluoromethyl-4-bromine two
Chlorotoluene 18%, o-trifluoromethyl-4-bromobenzaldehyde 70%.It is cooled to room temperature and adds 100mL water, 100mL
Dichloromethane extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 9.8g neighbour's fluoroform
Base-4-chlorobenzaldehyde.Yield 60%, GC purity is 91%.
Embodiment 14
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g (0.15mol) concentrated sulphuric acid, 20g
(0.33mol) acetic acid mixing, 70 DEG C are stirred 25 hours, are cooled to room temperature and add 100mL water, 100mL
Dichloromethane extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 11.6g neighbour's trifluoro
Methyl-4-bromobenzaldehyde.Yield 71%, GC purity is 97%.
Embodiment 15
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g (0.15mol) concentrated sulphuric acid, 20g
(0.33mol) acetic acid mixing, 120 DEG C are stirred 16 hours, are cooled to room temperature and add 100mL water, 100mL
Dichloromethane extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 13.1g neighbour's trifluoro
Methyl-4-bromobenzaldehyde.Yield 80%, GC purity is 94%.
Embodiment 16
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is the sulfur of 95%
Aqueous acid, 80 DEG C are stirred 16 hours, are cooled to room temperature and add 100mL water, 100mL dichloromethane
Extraction, organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 14.2g o-trifluoromethyl-4-bromine
Benzaldehyde.Yield 82%, GC purity is 98%.
Embodiment 17
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 17.7g zinc chloride and 100mL water,
Mixing, 100 DEG C are stirred 16 hours, are cooled to room temperature, and 100mL dichloromethane extracts, and organic facies is washed
To neutral, boiling off solvent, decompression distillation obtains 11g o-trifluoromethyl-4-bromobenzaldehyde.Yield 67%,
GC purity is 97%.
Embodiment 188
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 21.1g zinc sulfate and 100mL water,
Mixing, 100 DEG C are stirred 16 hours, are cooled to room temperature, and 100mL dichloromethane extracts, and organic facies is washed
To neutral, boiling off solvent, decompression distillation obtains 10g o-trifluoromethyl-4-bromobenzaldehyde.Yield 61%,
GC purity is 96%.
Embodiment 19
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 106g zinc chloride and 100mL water,
Mixing, 100 DEG C are stirred 16 hours, are cooled to room temperature, and 100mL dichloromethane extracts, and organic facies is washed
To neutral, boiling off solvent, decompression distillation obtains 10.6g o-trifluoromethyl-4-bromobenzaldehyde.Yield 65%,
GC purity is 91%.
Embodiment 20
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is 95% sulphuric acid
Aqueous solution, mixing, 130 DEG C are stirred 16 hours, are cooled to room temperature and add 100mL water, 100mL bis-
Chloromethanes extracts, and organic facies is washed to neutrality, boils off solvent, and decompression distillation obtains 10.3g neighbour's fluoroform
Base-4-bromobenzaldehyde.Yield 63%, GC purity is 87%.
Comparative example 11
By 114g o-trifluoromethyl-4-bromine dichlorotoleune, 210g 20% sodium hydroxide solution, 240g acetic acid,
0.1g tetrabutyl ammonium bromide, puts in the four-hole boiling flask that band is stirred at reflux, is warming up to 160 DEG C of backflows, pressure
Strong is 0.45MPa, and insulation reaction, after reacting 3 hours, by gas chromatographic analysis, o-trifluoromethyl
Benzene-4-bromobenzaldehyde peak area is 7.6%, is cooled to room temperature, and by reactant liquor sucking filtration, mother solution decompression steams
Acetic acid, adds 240g water, stirs stratification, separates organic layer, rectification under vacuum, collect 70-75 DEG C
The fraction of/0.095Mpa, obtains 5.7g o-trifluoromethyl-4-bromobenzaldehyde, GC area: 92.5%, receives
Rate: 6.0%.
Comparative example 12
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is 36% hydrochloric acid
Aqueous solution, 20g acetic acid mixes, refluxes 16 hours, by gas chromatographic analysis, o-trifluoromethyl-4-
Bromine dichlorotoleune 65%, o-trifluoromethyl-4-bromobenzaldehyde 30%.
Comparative example 13
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is the hydrogen of 48%
Bromic acid aqueous solution, 20g acetic acid mixes, refluxes 16 hours, by gas chromatographic analysis, o-trifluoromethyl
-4-bromine dichlorotoleune 60%, o-trifluoromethyl-4-bromobenzaldehyde 31%.
Comparative example 14
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is 57% hydrogen iodine
Aqueous acid, 20g acetic acid mixes, refluxes 16 hours, by gas chromatographic analysis, o-trifluoromethyl-4-
Bromine dichlorotoleune 58%, o-trifluoromethyl-4-bromobenzaldehyde 31%.
Comparative example 15
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is the salt of 36%
Aqueous acid mixes, and refluxes 16 hours, by gas chromatographic analysis, o-trifluoromethyl-4-bromine dichloromethane
Benzene 85%, o-trifluoromethyl-4-bromobenzaldehyde 5%.
Comparative example 16
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is the hydrogen of 48%
Bromic acid aqueous solution, refluxes 16 hours, by gas chromatographic analysis, o-trifluoromethyl-4-bromine dichloro
Toluene level 80%, o-trifluoromethyl-4-bromobenzaldehyde content 10%.
Comparative example 17
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g mass fraction is 57% hydrogen iodine
Aqueous acid mixes, and refluxes 16 hours, by gas chromatographic analysis, o-trifluoromethyl-4-bromine dichloromethane
Benzene 78%, o-trifluoromethyl-4-bromobenzaldehyde 10%.
Comparative example 18
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 15g concentrated sulphuric acid, 20g trifluoroacetic acid
Mixing, refluxes 16 hours, by gas chromatographic analysis, and o-trifluoromethyl-4-bromine dichlorotoleune 40%,
O-trifluoromethyl-4-bromobenzaldehyde 48%.
Comparative example 19
20g (0.065mol) o-trifluoromethyl-4-bromine dichlorotoleune, 17.7g zinc chloride and 100mL water,
Mixing, 60 DEG C are stirred 16 hours, are cooled to room temperature, and 100mL dichloromethane extracts, and organic facies is washed
To neutral, boiling off solvent, decompression distillation obtains 5g o-trifluoromethyl-4-bromobenzaldehyde.Yield 31%,
GC purity is 77%.
Claims (10)
1. the preparation method of an o-trifluoromethyl-4-halogenated benzaldehyde, it is characterised in that under it includes
Row method and steps:
Method one: under condition of no solvent, under the catalysis of acid, by o-trifluoromethyl-4-as shown in Equation 2
Halo dichlorotoleune and water carry out hydrolysis as follows, prepare o-trifluoromethyl as shown in Equation 3
-4-halogenated benzaldehyde,；Described acid is C1～C4The saturated unary fatty acid of straight chain and inorganic acid
Mixture or inorganic acid；Described inorganic acid is sulphuric acid and/or phosphoric acid；Described hydrolysis
Temperature be 70 DEG C～130 DEG C；
Method two: in water, under lewis acidic catalysis, by o-trifluoromethyl-4-as shown in Equation 2
Halo dichlorotoleune and water carry out hydrolysis as follows, prepare o-trifluoromethyl as shown in Equation 3
-4-halogenated benzaldehyde,；The temperature of described hydrolysis is 90 DEG C～100 DEG C；
Wherein, in compound 2 or compound 3, X is Br or I.
2. preparation method as claimed in claim 1, it is characterised in that in method one, described water
The temperature solving reaction is 80 DEG C～120 DEG C, preferably 90 DEG C～100 DEG C；Described sulphuric acid is concentrated sulphuric acid
Or oleum；Described concentrated sulphuric acid is preferably meant that the aqueous sulfuric acid that mass fraction is 85%～98%；
Described phosphoric acid is preferably meant that the phosphate aqueous solution that mass fraction is more than 85%；Above-mentioned % each means nothing
The quality of machine strong acid accounts for the percentage ratio of inorganic acid aqueous solution gross mass；Described C1～C4Straight chain saturated
Unary fatty acid is one or more of formic acid, acetic acid, propanoic acid and butanoic acid；Described C1～C4Straight chain
Saturated unary fatty acid with the mol ratio of o-trifluoromethyl-4-halo dichlorotoleune is as shown in Equation 2
2:1～20:1；Described inorganic acid rubs with o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2
That ratio is 2:1～20:1；And/or, described water and o-trifluoromethyl-4-halo dichloromethane as shown in Equation 2
The mol ratio of benzene is 0.5:1～10:1.
3. preparation method as claimed in claim 2, it is characterised in that in method one, described C1～C4
The saturated unary fatty acid of straight chain and o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2 mole
Ratio is 4:1～10:1；Described inorganic acid and o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2
Mol ratio be 4:1～10:1；And/or, described water and o-trifluoromethyl-4-halo two as shown in Equation 2
The mol ratio of chlorotoluene is 0.5:1～5:1.
4. preparation method as claimed in claim 1, it is characterised in that in method two, described road
Lewis acid is one or more in zinc chloride, iron chloride and zinc sulfate；Described lewis acid with such as formula
The mol ratio of the o-trifluoromethyl-4-halo dichlorotoleune shown in 2 is 1:1～20:1；And/or, described water
It is 1mL/g～20mL/g with the volume mass of o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2.
5. preparation method as claimed in claim 4, it is characterised in that in method two, described road
Lewis acid is 4:1～10:1 with the mol ratio of o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2；With
/ or, described water with the volume mass of o-trifluoromethyl-4-halo dichlorotoleune is as shown in Equation 2
5mL/g～10mL/g.
6. the preparation method as described in any one of Claims 1 to 5, it is characterised in that described neighbour three
The preparation method of methyl fluoride-4-halogenated benzaldehyde still further comprises the following step: in acetic acid, at sulphuric acid
Under catalysis, o-trifluoromethyl dichlorotoleune as shown in Equation 1 and halogenating agent are carried out choosing as follows
Selecting property halogenating reaction, prepares o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2,；Described
Halogenating agent be DBDMH or diiodo-glycolylurea；
In compound 2, X is Br or I.
7. preparation method as claimed in claim 6, it is characterised in that described selectivity halo is anti-
After should comprising the following steps: to mix acetic acid with sulphuric acid, then with o-trifluoromethyl dichloro as shown in Equation 1
Toluene mixes, and under conditions of 0～90 DEG C, adds halogenating agent, carries out described selectivity halogenating reaction.
8. preparation method as claimed in claim 7, it is characterised in that described selectivity halo is anti-
Ying Zhong, described sulphuric acid is concentrated sulphuric acid or oleum；Described concentrated sulphuric acid refers to that mass fraction is
The aqueous sulfuric acid of 85%～98%；The described temperature adding halogenating agent is 10～50 DEG C, preferably
25～40 DEG C；Described halogenating agent with the mol ratio of o-trifluoromethyl dichlorotoleune is as shown in Equation 1
0.5:1～3:1, preferably 0.5:1～1.5:1；Described acetic acid and o-trifluoromethyl two as shown in Equation 1
The mol ratio of chlorotoluene is 2:1～20:1, preferably 2:1～8:1；Described sulphuric acid with as shown in Equation 1
The mol ratio of o-trifluoromethyl dichlorotoleune is 2:1～20:1, preferably 2:1～8:1；And/or, described
Time of selectivity halogenating reaction be 2～40 hours, preferably 4～16 hours.
9. an o-trifluoromethyl-4-halo dichlorotoleune as shown in Equation 2:
Wherein, in compound 2, X is Br or I.
10. the preparation method of an o-trifluoromethyl-4-halo dichlorotoleune, it is characterised in that it comprises
The following step: in acetic acid, under the catalysis of sulphuric acid, by o-trifluoromethyl dichlorotoleune as shown in Equation 1
Carry out selectivity halogenating reaction as follows with halogenating agent, prepare described neighbour three as shown in Equation 2
Methyl fluoride-4-halo dichlorotoleune,；Described halogenating agent is two chlordantoins, DBDMH or two
Iodine glycolylurea；
Wherein, in compound 2, X is Cl, Br or I；The method of described selectivity halogenating reaction
Condition is as described in any one of claim 6～8.
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| CN115872844A (en) * | 2022-12-27 | 2023-03-31 | 上海筑裕新材料科技有限公司 | Preparation method of 3-bromo-4- (trifluoromethyl) benzaldehyde |
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