CN109369571A - One kind containing the bromo- 4- aldehyde radical diazosulfide of fluorine-substituted 7- and its synthetic method - Google Patents
One kind containing the bromo- 4- aldehyde radical diazosulfide of fluorine-substituted 7- and its synthetic method Download PDFInfo
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Abstract
It the invention belongs to optoelectronic materials technology, provides a kind of containing the bromo- 4- aldehyde radical diazosulfide of fluorine-substituted 7- and its synthetic method, comprising: by nitric acid dropping to dissolved in the sulfuric acid containing fluoroaniline, obtaining fluorine-containing nitroaniline；Fluorine-containing nitroaniline is restored to obtain fluorine-containing o-phenylenediamine with stannous chloride；Thionyl chloride is added dropwise in the chloroformic solution dissolved with fluorine-containing o-phenylenediamine, fluorine-containing diazosulfide is obtained；Fluorine-containing diazosulfide is flowed back in hydrobromic acid and bromine, obtains bromo-derivative；Bromo-derivative is reacted with NBS, obtains methyl list bromine substituent or the double bromine substituents of methyl；It flows back in formic acid by methyl list bromine substituent sodium periodate oxidation or by the double bromine substituents of methyl, obtains the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-.Raw material of the present invention is easy to get, and toxic step is not present, securely and reliably；It is produced suitable for amplification, efficiency is greatly improved；Solve the problems, such as that yield is extremely low, it is easily operated, it is at low cost, there is broader applications prospect.
Description
Technical field
The present invention relates to optoelectronic materials technologies, and in particular to a kind of bromo- 4- aldehyde radical benzo thiophene two containing fluorine-substituted 7-
Azoles and its synthetic method.
Background technique
Diazosulfide compound is widely used in the MOLECULE DESIGN of photoelectric material as a kind of important chromophoric group
With property research.And the bridging intermediate that the bromo- 4- aldehyde radical diazosulfide of 7- is important as one, it is closed in recent years by people
Note.
Currently, the preparation method of the bromo- 4- aldehyde radical diazosulfide of 7- mostly uses greatly J.Am.Chem.Soc., 2011,133
(40), 15822-15825, Adv.Funct.Mater., 2012,22 (6), 1291-1302 and J.Am.Chem.Soc.,
2015,137 (2), preparation method disclosed in 898-904.This method is starting material with methyl diazosulfide, by being cyclized,
Bromination, bromobenzyl program, last debrominate obtain product, and synthetic route is as follows:
Fluorine atom is introduced on the phenyl ring of the bromo- 4- aldehyde radical diazosulfide molecule of 7-, is shown after application more superior
Photoelectric properties.ACS Appl.Mater.Interfaces, 2017,9,37087-37093, Chem.Mater.2017,29,
The synthesis committed step of the bromo- 4- aldehyde radical diazosulfide of the fluorine-containing 7- reported in 8177-8186 all refers to diazosulfide ring
Upper introducing methyl, yield is extremely low, only 9.88%, greatly reduce the combined coefficient of finished product and meanwhile increase synthesis at
This.
Summary of the invention
For the defects in the prior art, the present invention provide it is a kind of containing the bromo- 4- aldehyde radical diazosulfide of fluorine-substituted 7- and
Its synthetic method, to avoid above-mentioned optoelectronic materials technology there are the problem of.
In a first aspect, the synthetic method of the bromo- 4- aldehyde radical diazosulfide provided by the invention containing fluorine-substituted 7-, including such as
Lower step:
Step S1, by nitric acid dropping to dissolved in the sulfuric acid containing fluoroaniline, obtaining fluorine-containing nitroaniline；
Step S2, it restores the fluorine-containing nitroaniline to obtain fluorine-containing o-phenylenediamine with stannous chloride；
Step S3, thionyl chloride is added dropwise in the chloroformic solution dissolved with the fluorine-containing o-phenylenediamine, obtains fluorine-containing benzo
Thiadiazoles；
Step S4, the fluorine-containing diazosulfide is flowed back in hydrobromic acid and bromine, obtains bromo-derivative；
Step S5, the bromo-derivative is reacted with NBS, obtains methyl list bromine substituent or the double bromine substituents of methyl；
Step S6, by the methyl list bromine substituent sodium periodate oxidation or by the double bromine substituents of the methyl in formic acid
Middle reflux obtains the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-.
Optionally, the concrete operations of the step S1 are as follows: at low temperature, being added dropwise to the concentrated sulfuric acid containing fluoroaniline for described
In, concentrated nitric acid is added dropwise in insulated and stirred 0.5-1h, and low-temp reaction 1-2h reacts at room temperature 12-20h, reaction solution is poured into ice water,
1-2h is stirred, the fluorine-containing nitroaniline is filtered to obtain；
Wherein, the cryogenic temperature range is -10 DEG C -0 DEG C, and the volume ratio containing fluoroaniline and the concentrated sulfuric acid is
1:10-20, the molar ratio containing fluoroaniline and the concentrated nitric acid are 1:1.1-1.2.
Optionally, the concrete operations of the step S2 are as follows: ethyl acetate and ethyl alcohol is added in the fluorine-containing nitroaniline
In the mixed solvent, stannous chloride is added, heating reaction 3-6h, reaction solution is poured into ice water, bicarbonate is used under nitrogen protection
Sodium water solution is adjusted to alkalinity, ethyl acetate extraction, and dry, concentration obtains the fluorine-containing o-phenylenediamine；
Wherein, the volume ratio of the ethyl acetate and the ethyl alcohol is 10:3, and heating temperature is 60-80 DEG C, the alkalinity
PH be 9-10.
Optionally, the concrete operations of the step S3 are as follows: the fluorine-containing o-phenylenediamine being dissolved in chloroformic solution, is added
Thionyl chloride is added dropwise in pyridine, and reaction solution is poured into water by back flow reaction 12-18h under nitrogen protection, and liquid separation obtains organic phase, does
Dry, concentration, obtains fluorine-containing diazosulfide；
Wherein, the volume fraction of the chloroformic solution is 15-20vol%, and the pyridine is that the fluorine-containing o-phenylenediamine is worked as
2-4 times of amount.
Optionally, the concrete operations of the step S4 are as follows: the fluorine-containing diazosulfide is dissolved in hydrobromic acid aqueous solution
In, bromine is added dropwise, is heated to reflux for 24 hours, it is cooling, filter to obtain the fluorine-containing diazosulfide of bromo；
Wherein, the volume fraction of the hydrobromic acid solution is 10-20vol%, and the bromine is the fluorine-containing benzo thiophene two
1.05-1.1 times of azoles equivalent.
Optionally, the concrete operations of the step S5 are as follows: the fluorine-containing diazosulfide of the bromo is dissolved in carbon tetrachloride
In, NBS is added, flows back for 24 hours, reaction solution is poured into water, liquid separation under nitrogen protection, organic phase is dry, is concentrated, and gained crude product is used
Methanol mashing, filters to obtain single bromine substituent or double bromine substituents；
Wherein, the volume fraction of carbon tetrachloride is 10-20vol%.
Optionally, it when the 1-1.1 equivalent that the NBS dosage is the fluorine-containing diazosulfide of bromo, obtains methyl list bromine and replaces
Object obtains the double bromine substituents of methyl when the 2.2-3 equivalent that the NBS dosage is the fluorine-containing diazosulfide of bromo.
Optionally, in the step S6 to the methyl list bromine substituent specific steps are as follows: by equivalent
Methyl list bromine substituent and sodium metaperiodate be added volume fraction be 10vol% DMF in, be heated to reflux 8h, be cooled to room temperature,
Reaction solution is poured into ice water, 0.5h is stirred, filters to obtain the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-.
Optionally, in the step S6 to the double bromine substituents of the methyl specific steps are as follows: methyl is double
Bromine substituent is added in the formic acid that volume fraction is 30vol%, is heated to reflux 8h, is cooled to room temperature, reaction solution is poured into ice
In water, 0.5h is stirred, the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- is filtered to obtain.
Second aspect, the present invention also provides a kind of bromo- 4- aldehyde radical diazosulfides containing fluorine-substituted 7-, are contained by described
The synthetic method of the fluorine-substituted bromo- 4- aldehyde radical diazosulfide of 7- synthesizes, the bromo- 4- aldehyde radical benzo thiophene two containing fluorine-substituted 7-
Azoles is specially the fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of 7-, and structural formula isNo. CAS is 2241215-37-0.
Technical effect of the invention:
1. raw material of the present invention is easy to get, toxic step is not present, more securely and reliably.
2. the present invention is suitable for amplification production, efficiency is greatly improved.
3. the present invention solves the problems, such as that yield is extremely low, easily operated, at low cost, there is wider application prospect.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art are briefly described.In all the appended drawings, similar element
Or part is generally identified by similar appended drawing reference.In attached drawing, each element or part might not be drawn according to actual ratio.
Fig. 1 is the anti-of the synthetic method of the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- of first embodiment of the invention
Answer flow chart；
Fig. 2 is the nuclear magnetic resonance figures of the fluoro- 7- methyl diazosulfide of the bromo- 5- of intermediate product 4- of the embodiment of the present invention 1；
Fig. 3 is the nuclear magnetic resonance figures of the bromo- 7- bromomethyl -5- fluorine diazosulfide of intermediate product 4- of the embodiment of the present invention 1；
Fig. 4 is the nuclear magnetic resonance of the bis- bromomethyl -5- fluorine diazosulfides of the bromo- 7- of intermediate product 4- of the embodiment of the present invention 1
Figure；
Fig. 5 is the nuclear magnetic resonance figures of the fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of final product 7- of the embodiment of the present invention 1.
Specific embodiment
It is described in detail below in conjunction with embodiment of the attached drawing to technical solution of the present invention.Following embodiment is only used for
Clearly illustrate technical solution of the present invention, therefore be intended only as example, and cannot be used as a limitation and limit protection of the invention
Range.
It should be noted that unless otherwise indicated, technical term or scientific term used in this application should be this hair
The ordinary meaning that bright one of ordinary skill in the art are understood.
Initial feed used by the embodiment of the present invention is containing fluoroaniline, specifically 4- fluoro-2-methylbenzene amine (CAS:452-
71-1), structural formula is
Fig. 1 is the anti-of the synthetic method of the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- of first embodiment of the invention
Answer flow chart.Referring to Fig. 1, the synthesis for the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- that first embodiment of the invention provides
Method includes the following steps:
Step S1, by nitric acid dropping to dissolved in the sulfuric acid containing fluoroaniline, obtaining fluorine-containing nitroaniline；
At low ambient temperatures, it being added dropwise to described in the concentrated sulfuric acid containing fluoroaniline, concentrated nitric acid is added dropwise in insulated and stirred 0.5-1h,
Low-temp reaction 1-2h reacts at room temperature 12-20h, reaction solution is poured into ice water, stirs 1-2h, filters described containing fluoronitrobenzene
Amine.
Wherein, the cryogenic temperature range is -10 DEG C -0 DEG C, and the volume ratio containing fluoroaniline and the concentrated sulfuric acid is
1:10-20, the molar ratio containing fluoroaniline and the concentrated nitric acid are 1:1.1-1.2.
The fluoro- 2- methyl -6- nitroaniline (CAS:147285-87-8) of fluorine-containing nitroaniline, specifically 4-, structural formula are
Step S2, it restores the fluorine-containing nitroaniline to obtain fluorine-containing o-phenylenediamine with stannous chloride；
The fluorine-containing nitroaniline is added to the in the mixed solvent of ethyl acetate and ethyl alcohol, stannous chloride is added, nitrogen is protected
The lower heating reaction 3-6h of shield, reaction solution is poured into ice water, is adjusted to alkalinity with sodium bicarbonate aqueous solution, ethyl acetate extraction is done
Dry, concentration, obtains the fluorine-containing o-phenylenediamine.
Wherein, the volume ratio of the ethyl acetate and the ethyl alcohol is 1:3, and heating temperature is 60-80 DEG C, the alkalinity
PH is 9-10.
The fluoro- 2- methyl-o-phenylenediamine of fluorine-containing o-phenylenediamine, specifically 4-, structural formula are
Step S3, thionyl chloride is added dropwise in the chloroformic solution dissolved with the fluorine-containing o-phenylenediamine, obtains fluorine-containing benzo
Thiadiazoles；
The fluorine-containing o-phenylenediamine is dissolved in chloroformic solution, pyridine is added, thionyl chloride is added dropwise, flows back under nitrogen protection
12-18h is reacted, reaction solution is poured into water, liquid separation obtains organic phase, and dry, concentration obtains fluorine-containing diazosulfide.
Wherein, the volume fraction of the chloroformic solution is 15-20vol%, and the pyridine is that the fluorine-containing o-phenylenediamine is worked as
2-4 times of amount.
Fluorine-containing diazosulfide, specifically 4- fluoro-2-methylbenzene and thiadiazoles, structural formula are
Step S4, the fluorine-containing diazosulfide is flowed back in hydrobromic acid and bromine, obtains bromo-derivative；
The fluorine-containing diazosulfide is dissolved in hydrobromic acid aqueous solution, bromine is added dropwise, is heated to reflux for 24 hours, it is cooling, it filters
Obtain the fluorine-containing diazosulfide of bromo；
Wherein, the volume fraction of the hydrobromic acid solution is 10-20vol%, and the bromine is the fluorine-containing benzo thiophene two
1.05-1.1 times of azoles equivalent.
The fluorine-containing diazosulfide of bromo, the fluoro- 2- methyl -5- bromine diazosulfide of specifically 4-, structural formula are
Step S5, the bromo-derivative is reacted with NBS, obtains methyl list bromine substituent or the double bromine substituents of methyl；
The fluorine-containing diazosulfide of the bromo is dissolved in carbon tetrachloride, NBS is added, flows back for 24 hours under nitrogen protection, it will be anti-
Answer liquid to be poured into water, liquid separation, organic phase is dry, concentration, and gained crude product is beaten with methanol, filter single bromine substituent or double bromines take
For object；
Wherein, the volume fraction of carbon tetrachloride is 10-20vol%.
When the 1-1.1 equivalent that the NBS dosage is the fluorine-containing diazosulfide of bromo, methyl list bromine substituent is obtained, institute is worked as
The 2.2-3 equivalent that NBS dosage is the fluorine-containing diazosulfide of bromo is stated, the double bromine substituents of methyl are obtained.
Methyl list bromine substituent is specifically the bromo- 7- bromomethyl -5- fluorine diazosulfide of 4-, and structural formula is
The double bromine substituents of methyl are specifically the bis- bromomethyl -5- fluorine diazosulfides of the bromo- 7- of 4-, and structural formula is
Step S6, by the methyl list bromine substituent sodium periodate oxidation or by the double bromine substituents of the methyl in formic acid
Middle reflux obtains the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-.
To the methyl list bromine substituent specific steps are as follows: by the methyl list bromine substituent of equivalent and high iodine
Sour sodium is added in the DMF that volume fraction is 10vol%, is heated to reflux 8h, is cooled to room temperature, reaction solution is poured into ice water,
0.5h is stirred, the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- is filtered to obtain.
To the double bromine substituents of the methyl specific steps are as follows: being by the double bromine substituents addition volume fractions of methyl
In the formic acid of 30vol%, it is heated to reflux 8h, is cooled to room temperature, reaction solution is poured into ice water, 0.5h is stirred, filters to contain
The fluorine-substituted bromo- 4- aldehyde radical diazosulfide of 7-.
The bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- is specifically the fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of 7-, structure
Formula is
Embodiment 1
1. heat preservation is stirred in the 98vol% concentrated sulfuric acid that the 4- fluoro-2-methylbenzene amine of 11.26g is added dropwise to 100ml by -10 DEG C
0.5h is mixed, the 65vol% concentrated nitric acid of 6.9ml is added dropwise, low-temp reaction 1h reacts at room temperature 12h, reaction solution is poured into ice water, is stirred
Mix 1h, filter 8.86g the fluoro- 2- methyl -6- nitroaniline of 4-.
2. the mixing that 50ml ethyl acetate and 150ml ethyl alcohol is added in the fluoro- 2- methyl -6- nitroaniline of the 4- of 8.86g is molten
In agent, 50ml stannous chloride is added, is heated to 60 DEG C of reaction 6h under nitrogen protection, reaction solution is poured into ice water, bicarbonate is used
It is 9 that sodium water solution, which is adjusted to pH, ethyl acetate extraction, and dry, concentration obtains the fluoro- 2- methyl-o-phenylenediamine of 4- of 7.52g.
3. the fluoro- 2- methyl-o-phenylenediamine of the 4- of 7.52g to be dissolved in the chloroformic solution for the 15vol% that volume fraction is 80ml
In, 8.49g pyridine is added, 12ml thionyl chloride is added dropwise, reaction solution is poured into water, liquid separation by back flow reaction 12h under nitrogen protection
Organic phase is obtained, dry, concentration obtains the 4- fluoro-2-methylbenzene and thiadiazoles of 5.58g.
4. by the 4- fluoro-2-methylbenzene of 5.58g and thiadiazoles to be dissolved in the hydrobromic acid that 80ml volume fraction is 20vol% water-soluble
In liquid, 2.79g bromine is added dropwise, is heated to reflux for 24 hours, it is cooling, filter 2.47g the fluoro- 2- methyl -5- bromine diazosulfide of 4-.
5. the fluoro- 2- methyl -5- bromine diazosulfide of the 4- of 2.47g is added in 100ml three-necked flask, then to three-necked flask
In pour into 30ml volume fraction be 20vol% carbon tetrachloride, 30min nitrogen is then blasted into three-necked flask, by 1.85 grams
NBS is added in above-mentioned solution, and 30min nitrogen is then blasted into three-necked flask, reaction solution is heated to reflux for 24 hours, by reaction solution
It is poured into 100ml ice water, liquid separation, organic phase is dry, concentration.Methanol is added in the solid obtained after to above-mentioned concentration
20ml stirs 30min.It filters, it is dry, obtain the bromo- 7- bromomethyl -5- fluorobenzene of 2.45 grams of off-white powder 4- that yield is 78%
And thiadiazoles.
6. 100ml volume point is added in the bromo- 7- bromomethyl -5- fluorine diazosulfide of the 4- of 2.45g and 2.9g sodium metaperiodate
Number is to be heated to reflux 8h in the DMF of 10vol%, be cooled to room temperature, reaction solution is poured into ice water, stirs 0.5h, filters
The fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of the 7- of 1.88g.
Embodiment 2
1. heat preservation is stirred in the 98vol% concentrated sulfuric acid that the 4- fluoro-2-methylbenzene amine of 11.26g is added dropwise to 150ml by -5 DEG C
40min is mixed, the 65vol% concentrated nitric acid of 7.2ml is added dropwise, low-temp reaction 1.5h reacts at room temperature 15h, reaction solution is poured into ice water,
Stir 1.5h, filter 8.92g the fluoro- 2- methyl -6- nitroaniline of 4-.
2. the mixing that 50ml ethyl acetate and 150ml ethyl alcohol is added in the fluoro- 2- methyl -6- nitroaniline of the 4- of 8.92g is molten
In agent, 50ml stannous chloride is added, is heated to 70 DEG C of reaction 5h under nitrogen protection, reaction solution is poured into ice water, bicarbonate is used
It is 9 that sodium water solution, which is adjusted to pH, ethyl acetate extraction, and dry, concentration obtains the fluoro- 2- methyl-o-phenylenediamine of 4- of 7.88g.
3. the fluoro- 2- methyl-o-phenylenediamine of the 4- of 7.88g to be dissolved in the chloroformic solution for the 20vol% that volume fraction is 80ml
In, 10g pyridine is added, 12ml thionyl chloride is added dropwise, reaction solution is poured into water, liquid separation obtains by back flow reaction 15h under nitrogen protection
Organic phase, dry, concentration obtain the 4- fluoro-2-methylbenzene and thiadiazoles of 6.62g.
4. by the 4- fluoro-2-methylbenzene of 6.62g and thiadiazoles to be dissolved in the hydrobromic acid that 80ml volume fraction is 15vol% water-soluble
In liquid, 2.88g bromine is added dropwise, is heated to reflux for 24 hours, it is cooling, filter 4.53g the fluoro- 2- methyl -5- bromine diazosulfide of 4-.
5. the fluoro- 2- methyl -5- bromine diazosulfide of the 4- of 4.53g is added in 100ml three-necked flask, then to three-necked flask
In pour into 30ml volume fraction be 15vol% carbon tetrachloride, 30min nitrogen is then blasted into three-necked flask, by 1.85 grams
NBS is added in above-mentioned solution, and 30min nitrogen is then blasted into three-necked flask, reaction solution is heated to reflux for 24 hours, by reaction solution
It is poured into 100ml ice water, liquid separation, organic phase is dry, concentration.Methanol is added in the solid obtained after to above-mentioned concentration
20ml stirs 30min.It filters, it is dry, obtain the bromo- 7- bromomethyl -5- fluorine diazosulfide of 2.86 grams of off-white powder 4-.
6. the bis- bromomethyl -5- fluorine diazosulfides of the bromo- 7- of 2.86 grams of 4- are added in 100ml three-necked flasks, then to three
The formic acid that 80ml volume fraction is 30vol% is poured into mouth flask, and 30min nitrogen is then blasted into three-necked flask, will be reacted
Liquid is heated to reflux 8h.Reaction solution is poured into 100ml ice water, 30min is stirred.It filtering, solid is washed with 5ml methanol, and it is dry,
Obtain 1.58 grams of the fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of buff white solid 7- that yield is 86%.
Embodiment 3
1. in the 98vol% concentrated sulfuric acid that the 4- fluoro-2-methylbenzene amine of 11.26g is added dropwise to 200ml by 0 DEG C, insulated and stirred
The 65vol% concentrated nitric acid of 7.5ml is added dropwise in 1h, and low-temp reaction 2h reacts at room temperature 20h, reaction solution is poured into ice water, stirs 2h,
Filter 8.42g the fluoro- 2- methyl -6- nitroaniline of 4-.
2. the mixing that 50ml ethyl acetate and 150ml ethyl alcohol is added in the fluoro- 2- methyl -6- nitroaniline of the 4- of 8.42g is molten
In agent, 50ml stannous chloride is added, is heated to 80 DEG C of reaction 3h under nitrogen protection, reaction solution is poured into ice water, bicarbonate is used
It is 10 that sodium water solution, which is adjusted to pH, ethyl acetate extraction, and dry, concentration obtains the fluoro- 2- methyl-o-phenylenediamine of 4- of 7.05g.
3. the fluoro- 2- methyl-o-phenylenediamine of the 4- of 7.05g to be dissolved in the chloroformic solution for the 20vol% that volume fraction is 80ml
In, 17.0g pyridine is added, 12ml thionyl chloride is added dropwise, reaction solution is poured into water, liquid separation by back flow reaction 18h under nitrogen protection
Organic phase is obtained, dry, concentration obtains the 4- fluoro-2-methylbenzene and thiadiazoles of 5.99g.
4. by the 4- fluoro-2-methylbenzene of 5.99g and thiadiazoles to be dissolved in the hydrobromic acid that 80ml volume fraction is 10vol% water-soluble
In liquid, 2.92g bromine is added dropwise, is heated to reflux for 24 hours, it is cooling, filter 3.21g the fluoro- 2- methyl -5- bromine diazosulfide of 4-.
5. the fluoro- 2- methyl -5- bromine diazosulfide of the 4- of 3.21g is added in 100ml three-necked flask, then to three-necked flask
In pour into 30ml volume fraction be 10vol% carbon tetrachloride, 30min nitrogen is then blasted into three-necked flask, by 1.85 grams
NBS is added in above-mentioned solution, and 30min nitrogen is then blasted into three-necked flask, reaction solution is heated to reflux for 24 hours, by reaction solution
It is poured into 100ml ice water, liquid separation, organic phase is dry, concentration.Methanol is added in the solid obtained after to above-mentioned concentration
20ml stirs 30min.It filters, it is dry, obtain the bromo- 7- bromomethyl -5- fluorine diazosulfide of 2.75 grams of off-white powder 4-.
6. 100ml volume point is added in the bromo- 7- bromomethyl -5- fluorine diazosulfide of the 4- of 2.75g and 2.9g sodium metaperiodate
Number is to be heated to reflux 8h in the DMF of 10vol%, be cooled to room temperature, reaction solution is poured into ice water, stirs 0.5h, filters
The fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of the 7- of 2.03g.
About embodiment 1 intermediate product and final product nuclear magnetic resonance map referring to fig. 2-5,
The data of the bromo- 7- bromomethyl -5- fluorine diazosulfide of intermediate product 4- are as follows:
1H-NMR:7.59 (d, 1H), 4.92 (s, 2H).
The data of the fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of the 7- finally obtained are as follows:
1H-NMR:10,79 (s, 1H), 8.09 (s, 1H).
Unless specifically stated otherwise, the numerical value otherwise illustrated in these embodiments is not limit the scope of the invention.?
In all examples shown and described herein, unless otherwise prescribed, any occurrence should be construed as merely illustratively, and
Not by way of limitation, therefore, other examples of exemplary embodiment can have different values.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme should all cover within the scope of the claims and the description of the invention.
Claims (10)
1. a kind of synthetic method of the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-, which comprises the steps of:
Step S1, by nitric acid dropping to dissolved in the sulfuric acid containing fluoroaniline, obtaining fluorine-containing nitroaniline；
Step S2, it restores the fluorine-containing nitroaniline to obtain fluorine-containing o-phenylenediamine with stannous chloride；
Step S3, thionyl chloride is added dropwise in the chloroformic solution dissolved with the fluorine-containing o-phenylenediamine, obtains fluorine-containing benzo thiophene two
Azoles；
Step S4, the fluorine-containing diazosulfide is flowed back in hydrobromic acid and bromine, obtains bromo-derivative；
Step S5, the bromo-derivative is reacted with NBS, obtains methyl list bromine substituent or the double bromine substituents of methyl；
Step S6, it is returned in formic acid by the methyl list bromine substituent sodium periodate oxidation or by the double bromine substituents of the methyl
Stream, obtains the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-.
2. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 1 containing fluorine-substituted 7-, feature exist
In the concrete operations of the step S1 are as follows: at low temperature, being added dropwise to described in the concentrated sulfuric acid containing fluoroaniline, insulated and stirred
Concentrated nitric acid is added dropwise in 0.5-1h, and low-temp reaction 1-2h reacts at room temperature 12-20h, reaction solution is poured into ice water, stirs 1-2h, takes out
Filter to obtain the fluorine-containing nitroaniline；
Wherein, the cryogenic temperature range is -10 DEG C -0 DEG C, and the volume ratio containing fluoroaniline and the concentrated sulfuric acid is 1:
10-20, the molar ratio containing fluoroaniline and the concentrated nitric acid are 1:1.1-1.2.
3. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 1 containing fluorine-substituted 7-, feature exist
In the concrete operations of the step S2 are as follows: the fluorine-containing nitroaniline is added to the in the mixed solvent of ethyl acetate and ethyl alcohol,
Stannous chloride is added, heating reaction 3-6h, reaction solution is poured into ice water, is adjusted to alkali with sodium bicarbonate aqueous solution under nitrogen protection
Property, ethyl acetate extraction, dry, concentration obtains the fluorine-containing o-phenylenediamine；
Wherein, the volume ratio of the ethyl acetate and the ethyl alcohol is 10:3, and heating temperature is 60-80 DEG C, the pH of the alkalinity
For 9-10.
4. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 1 containing fluorine-substituted 7-, feature exist
In the concrete operations of the step S3 are as follows: the fluorine-containing o-phenylenediamine being dissolved in chloroformic solution, pyridine is added, is added dropwise two
Chlorine sulfoxide, back flow reaction 12-18h under nitrogen protection, reaction solution is poured into water, and liquid separation obtains organic phase, and dry, concentration must contain
Fluorine diazosulfide；
Wherein, the volume fraction of the chloroformic solution is 15-20vol%, and the pyridine is the fluorine-containing o-phenylenediamine equivalent
2-4 times.
5. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 1 containing fluorine-substituted 7-, feature exist
In the concrete operations of the step S4 are as follows: the fluorine-containing diazosulfide is dissolved in hydrobromic acid aqueous solution, bromine is added dropwise,
It is heated to reflux for 24 hours, it is cooling, filter to obtain the fluorine-containing diazosulfide of bromo；
Wherein, the volume fraction of the hydrobromic acid solution is 10-20vol%, and the bromine is that the fluorine-containing diazosulfide is worked as
1.05-1.1 times of amount.
6. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 1 containing fluorine-substituted 7-, feature exist
In the concrete operations of the step S5 are as follows: the fluorine-containing diazosulfide of the bromo being dissolved in carbon tetrachloride, NBS, nitrogen is added
It flows back under gas shielded for 24 hours, reaction solution is poured into water, liquid separation, organic phase is dry, is concentrated, and gained crude product is beaten with methanol, is filtered
Obtain single bromine substituent or double bromine substituents；
Wherein, the volume fraction of carbon tetrachloride is 10-20vol%.
7. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 6 containing fluorine-substituted 7-, feature exist
In when the 1-1.1 equivalent that the NBS dosage is the fluorine-containing diazosulfide of bromo, acquisition methyl list bromine substituent, as the NBS
Dosage is the 2.2-3 equivalent of the fluorine-containing diazosulfide of bromo, obtains the double bromine substituents of methyl.
8. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 1 containing fluorine-substituted 7-, feature exist
In, in the step S6 to the methyl list bromine substituent specific steps are as follows: the methyl list bromine of equivalent is taken
It is added for object and sodium metaperiodate in the DMF that volume fraction is 10vol%, is heated to reflux 8h, is cooled to room temperature, reaction solution is poured into
Into ice water, 0.5h is stirred, the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- is filtered to obtain.
9. the synthetic method of the bromo- 4- aldehyde radical diazosulfide according to claim 1 containing fluorine-substituted 7-, feature exist
In, in the step S6 to the double bromine substituents of the methyl specific steps are as follows: the double bromine substituents of methyl are added
Volume fraction is to be heated to reflux 8h in the formic acid of 30vol%, be cooled to room temperature, reaction solution is poured into ice water, is stirred
0.5h filters to obtain the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-.
10. a kind of bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7-, which is characterized in that by any one of claim 1-9 institute
The synthetic method for the bromo- 4- aldehyde radical diazosulfide containing fluorine-substituted 7- stated synthesizes, the bromo- 4- aldehyde radical benzene containing fluorine-substituted 7-
And thiadiazoles is specially the fluoro- 4- aldehyde radical diazosulfide of the bromo- 6- of 7-, structural formula isNo. CAS is 2241215-
37-0。
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