CN107522624A - A kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen - Google Patents
A kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen Download PDFInfo
- Publication number
- CN107522624A CN107522624A CN201710806731.9A CN201710806731A CN107522624A CN 107522624 A CN107522624 A CN 107522624A CN 201710806731 A CN201710806731 A CN 201710806731A CN 107522624 A CN107522624 A CN 107522624A
- Authority
- CN
- China
- Prior art keywords
- phenyl
- hydrogen
- production
- benzene substituted
- compounds process
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2/00—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms
- C07C2/86—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by condensation between a hydrocarbon and a non-hydrocarbon
- C07C2/88—Growth and elimination reactions
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
To solve the deficiencies in the prior art, the invention provides a kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen, this method adds response matrix and attack reagent first in reaction vessel, and mixes；Then, catalyst is added in said mixture, and is well mixed；Afterwards, by above-mentioned well mixed material, reacted 12 48 hours at 80 120 DEG C；Finally, solvent and purified product are removed, obtains the substitution product of the phenyl monosubstituted phenyl α hydrogen.The response matrix is：Contain the compound that at least one α hydrogen is connected with phenyl and phenyl；The attack reagent is：Phenylboric acid pinacol ester.The catalyst is：The mixture of di-t-butyl peroxide and acetylacetone cobalt.Cost-saved 50,000 yuans of 1000 grams of bagodryl hydrochlorides are synthesized using synthetic method of the present invention.
Description
Technical field
The invention belongs to change and thing synthesis technical field, and in particular to a kind of compound preparation side of benzene substituted-phenyl α hydrogen
Method.
Background technology
The hydrocarbon being made up of carbon and protium generally existing in nature, it is natural and synthesis hydrocarbon
Compound has important and is widely applied in many commercial fields, and effect of such compound in medicinal chemistry arts especially makes
People is interested.Diphenyl-methane is a kind of important medicine, pesticide intermediate, is had a wide range of applications in medicine, pesticide field
There is cholinolytic, calmness, anti-cinetosis and antiemetic effect, diphenhydramine to be exactly for prospect, the compound much synthesized by diphenyl-methane
A kind of conventional medicine based on diphenyl-methane.Carry out and the Study of synthesis method tool of diphenyl-methane is of great significance.
Traditional diphenyl-methane synthetic method is：Benzylic halides and phenyl boronate coupling reaction.Using toluene synthesizing diphenyl methane
Method it is considerably less.Following technical disadvantages be present in the existing method by toluene synthesizing diphenyl methane：First, need to use in reaction
Special Photoreactor and light-sensitive catalyst；Second, course of reaction needs to add substantial amounts of Phosphine ligands or nitrogen ligand, and this is to production
Thing purifying brings very big inconvenience.Also, because light-catalyzed reaction has very strong activation capacity, therefore easily lead to hydrogen substitution
In course of reaction due in reaction system the proportioning of part response matrix and attack reagent be unsatisfactory for 1:1, taken so as to which more hydrogen occur
Generation reaction, causes accessory substance to increase, further increases the purifying difficulty of product.The preparation process of diphenhydramine equally exists class
As problem.
The content of the invention
The present invention for single hydrogen substitution reaction of existing diphenyl-methane, diphenhydramine need to use special Photoreactor with
Light-sensitive catalyst；And need to add substantial amounts of Phosphine ligands or nitrogen ligand, the problem of causing product purification extremely difficult,
A kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen is provided, this method can be used for preparing diphenyl-methane, diphenhydramine, and
Overcome at least one in above mentioned problem.Its process includes：First, response matrix and attack reagent are added in reaction vessel, and is mixed
Close.Then, catalyst is added in said mixture, and is well mixed.Afterwards, by above-mentioned well mixed material, in 80-
12-48 hours are reacted at 120 DEG C.Finally, solvent and purified product are removed, obtains the substitution of the phenyl monosubstituted phenyl α hydrogen
Product.
Further, the response matrix is：Contain the compound that at least one α hydrogen is connected with phenyl and phenyl.
Further, the attack reagent is：Phenylboric acid pinacol ester.
Further, the catalyst is：The mixture of di-t-butyl peroxide and acetylacetone cobalt.
Further, the ratio between addition of the di-t-butyl peroxide and acetylacetone cobalt, is calculated as according to molfraction：
Di-t-butyl peroxide：Acetylacetone cobalt=50-150:1.
Further, the ratio between addition of the di-t-butyl peroxide and acetylacetone cobalt, is calculated as according to molfraction：
Di-t-butyl peroxide：Acetylacetone cobalt=80-100:1.
Further, the addition of the catalyst, according to molfraction meter, for 2-6 times of response matrix addition.
Further, the ratio between addition of the response matrix and attack reagent, is calculated as according to molfraction：Reactive group
Matter：Attack reagent=1:0.5-2.
Further, the method for removing solvent includes：Distillation under vacuum removes liquid phase part.The purified product
Method includes：The column chromatography for separation method of purification purifies to product.
Further, the response matrix is toluene.The substitution product of the phenyl monosubstituted phenyl α hydrogen is hexichol first
Alkane.
Further, the response matrix is 2- benzyloxies-N, N- dimethyl amine.The phenyl monosubstituted phenyl α hydrogen
Substitution product be diphenhydramine.
Further, the diphenhydramine is dissolved in ethanol solution first, the addition of the ethanol solution, with mole
Number meter, for 30-80 times of diphenhydramine.Dry hydrogen chloride gas is then passed to saturation.It is stirred at room temperature afterwards
0.5-5 hours.Solvent is finally removed, obtains bagodryl hydrochloride.
The present invention at least has one of the following advantages：
1. in the substitution reaction system of the present invention, it is not necessary to use special Photoreactor and light-sensitive catalyst and reacted
Journey need not add any Phosphine ligands or nitrogen ligand.Therefore industrialized production difficulty is small, and cost is relatively low, and product purification is relative to be held
Easily.Wherein using synthetic method of the present invention cost-saved 50,000 yuans of 1000 grams of bagodryl hydrochlorides of synthesis.
2. using the substitution reaction system of the present invention, hydrogen substitution occurs essentially according to the proportioning of response matrix and attack reagent
React, the substitution accessory substance outside proportioning is less, reduce further the purifying difficulty of product.
3. the reagent toxicity selected by reaction system of the present invention is relatively low, possess higher security compared with prior art, and
Course of reaction is simple, easily-controllable, it is possible to achieve scale industrial production.
Embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, below to of the invention further detailed
Explanation.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not intended to limit the present invention.
Embodiment 1
A kind of preparation method of diphenyl-methane, it is included in addition 1mol toluene, 1mol phenyl boron in 100mL there-necked flask
Sour pinacol ester, 4mol di-t-butyl peroxide (DTBP), 0.05mol acetylacetone cobalt, react 24 hours at 100 DEG C,
Distillation under vacuum removes liquid phase part, and residue is purified using the column chromatography for separation method of purification, obtains diphenyl-methane 0.95mol.
Embodiment 2
A kind of preparation method of diphenyl-methane, it is included in addition 1mol toluene, 1mol phenyl boron in 100mL there-necked flask
Sour pinacol ester, 2mol di-t-butyl peroxide (DTBP), 0.02mol acetylacetone cobalt, react 48 hours at 80 DEG C, subtract
The way of distillation is pressed to remove liquid phase part, residue is purified using the column chromatography for separation method of purification, obtains diphenyl-methane 0.94mol.
Embodiment 3
A kind of preparation method of diphenyl-methane, it is included in addition 1mol toluene, 1mol phenyl boron in 100mL there-necked flask
Sour pinacol ester, 5.94mol di-t-butyl peroxide (DTBP), 0.06mol acetylacetone cobalt, reaction 12 is small at 120 DEG C
When, distillation under vacuum removes liquid phase part, and residue is purified using the column chromatography for separation method of purification, obtains diphenyl-methane 0.97mol.
Embodiment 4
A kind of preparation method of diphenyl-methane, it is included in addition 1mol toluene, 1mol phenyl boron in 100mL there-necked flask
Sour pinacol ester, 3mol di-t-butyl peroxide (DTBP), 0.015mol acetylacetone cobalt, react 24 hours at 100 DEG C,
Distillation under vacuum removes liquid phase part, and residue is purified using the column chromatography for separation method of purification, obtains diphenyl-methane 0.94mol.
Embodiment 5
A kind of preparation method of diphenyl-methane, it is included in addition 1mol toluene, 1mol phenyl boron in 100mL there-necked flask
Sour pinacol ester, 3mol di-t-butyl peroxide (DTBP), 0.02mol acetylacetone cobalt, react 24 hours at 100 DEG C,
Distillation under vacuum removes liquid phase part, and residue is purified using the column chromatography for separation method of purification, obtains diphenyl-methane 0.94mol.
Embodiment 6
A kind of preparation method of diphenhydramine, 10mmol 2- benzyloxies-N, N- diformazan is added in 100mL there-necked flask
Base ethamine, 10mmol phenylboric acid pinacol ester, 40mmol di-t-butyl peroxide (DTBP), 0.5mmol levulinic
Ketone cobalt, react 24 hours at 100 DEG C, distillation under vacuum removes liquid phase part, is purified using the column chromatography for separation method of purification, obtains benzene
Extra large Lamine 9.5mmol.
Embodiment 7
A kind of preparation method of diphenhydramine, 10mmol 2- benzyloxies-N, N- diformazan is added in 100mL there-necked flask
Base ethamine, 10mmol phenylboric acid pinacol ester, 30mmol di-t-butyl peroxide (DTBP), 0.3mmol levulinic
Ketone cobalt, react 48 hours at 80 DEG C, distillation under vacuum removes liquid phase part, is purified using the column chromatography for separation method of purification, obtains benzene
Extra large Lamine 9.6mmol.
Embodiment 8
A kind of preparation method of diphenhydramine, 10mmol 2- benzyloxies-N, N- diformazan is added in 100mL there-necked flask
Base ethamine, 10mmol phenylboric acid pinacol ester, 40mmol di-t-butyl peroxide (DTBP), 0.8mmol levulinic
Ketone cobalt, react 12 hours at 120 DEG C, distillation under vacuum removes liquid phase part, is purified using the column chromatography for separation method of purification, obtains benzene
Extra large Lamine 9.6mmol.
Embodiment 9
A kind of preparation method of diphenhydramine, 10mmol 2- benzyloxies-N, N- diformazan is added in 100mL there-necked flask
Base ethamine, 10mmol phenylboric acid pinacol ester, 30mmol di-t-butyl peroxide (DTBP), 0.2mmol levulinic
Ketone cobalt, react 24 hours at 100 DEG C, distillation under vacuum removes liquid phase part, is purified using the column chromatography for separation method of purification, obtains benzene
Extra large Lamine 9.5mmol.
Embodiment 10
A kind of preparation method of bagodryl hydrochloride, using the preparation method of any diphenhydramines of embodiment 6-9, system
After diphenhydramine is obtained, gained diphenhydramine is dissolved in 0.35mol ethanol solution.Then pass to dry hydrogen chloride gas
Body is stirred at room temperature 1 hour, decompression boils off solvent, obtains bagodryl hydrochloride to saturation.
Embodiment 11
A kind of preparation method of bagodryl hydrochloride, using the preparation method of any diphenhydramines of embodiment 6-9, system
After diphenhydramine is obtained, choose gained diphenhydramine 5mmol and be dissolved in 0.4mol ethanol solution.Then pass to dry chlorine
Change hydrogen to saturation, be stirred at room temperature 5 hours, decompression boils off solvent, obtains bagodryl hydrochloride.
Embodiment 12
A kind of preparation method of bagodryl hydrochloride, using the preparation method of any diphenhydramines of embodiment 6-9, system
After diphenhydramine is obtained, choose gained diphenhydramine 5mmol and be dissolved in 0.15mol ethanol solution.Then pass to dry
Hydrogen chloride gas is stirred at room temperature 0.5 hour, decompression boils off solvent, obtains bagodryl hydrochloride to saturation.
Embodiment 13
A kind of preparation method of bagodryl hydrochloride, using the preparation method of any diphenhydramines of embodiment 6-9, system
After diphenhydramine is obtained, choose gained diphenhydramine 5mmol and be dissolved in 0.25mol ethanol solution.Then pass to dry
Hydrogen chloride gas is stirred at room temperature 2 hours, decompression boils off solvent, obtains bagodryl hydrochloride to saturation.
The present invention at least has one of the following advantages：
1. in the substitution reaction system of the present invention, it is not necessary to use special Photoreactor and light-sensitive catalyst and reacted
Journey need not add any Phosphine ligands or nitrogen ligand.Therefore industrialized production difficulty is small, and cost is relatively low, and product purification is relative to be held
Easily.Wherein using synthetic method of the present invention cost-saved 50,000 yuans of 1000 grams of bagodryl hydrochlorides of synthesis.
2. using the substitution reaction system of the present invention, hydrogen substitution occurs essentially according to the proportioning of response matrix and attack reagent
React, the substitution accessory substance outside proportioning is less, reduce further the purifying difficulty of product.
3. the reagent toxicity selected by reaction system of the present invention is relatively low, possess higher security compared with prior art, and
Course of reaction is simple, easily-controllable, it is possible to achieve scale industrial production.
It should be noted that and understand, in the case of the spirit and scope required by not departing from the claims in the present invention, energy
Enough present invention to foregoing detailed description make various modifications and improvements.It is therefore desirable to protection technical scheme scope not by
The limitation of given any specific exemplary teachings.
Claims (10)
1. a kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen, it is characterised in that add reactive group in reaction vessel first
Matter and attack reagent, and mix；Then, catalyst is added in said mixture, and is well mixed；Afterwards, by above-mentioned mixing
Uniform material, 12-48 hours are reacted at 80-120 DEG C；Finally, solvent and purified product are removed, the phenyl list is obtained and takes
For the substitution product of phenyl α hydrogen；
The response matrix is：Contain the compound that at least one α hydrogen is connected with phenyl and phenyl；
The attack reagent is：Phenylboric acid pinacol ester.
2. the compounds process for production thereof of benzene substituted-phenyl α hydrogen according to claim 1, it is characterised in that the catalyst is：
The mixture of di-t-butyl peroxide and acetylacetone cobalt.
3. the compounds process for production thereof of benzene substituted-phenyl α hydrogen according to claim 2, it is characterised in that the peroxidating two
The ratio between addition of the tert-butyl group and acetylacetone cobalt, is calculated as according to molfraction：Di-t-butyl peroxide：Acetylacetone cobalt=
50-150:1。
4. the compounds process for production thereof of benzene substituted-phenyl α hydrogen according to claim 3, it is characterised in that the peroxidating two
The ratio between addition of the tert-butyl group and acetylacetone cobalt, is calculated as according to molfraction：Di-t-butyl peroxide：Acetylacetone cobalt=
80-100:1。
5. the compounds process for production thereof of benzene substituted-phenyl α hydrogen according to claim 1, it is characterised in that the catalyst
Addition, according to molfraction meter, for 2-6 times of response matrix addition.
6. the compounds process for production thereof of benzene substituted-phenyl α hydrogen according to claim 1, it is characterised in that the response matrix
The ratio between with the addition of attack reagent, it is calculated as according to molfraction, response matrix：Attack reagent=1:1.
7. the compounds process for production thereof of benzene substituted-phenyl α hydrogen according to claim 1, it is characterised in that the removal solvent
Method include：Distillation under vacuum removes liquid phase part；The method of the purified product includes：The column chromatography for separation method of purification is to production
Thing is purified.
8. according to the compounds process for production thereof of any benzene substituted-phenyl α hydrogen of claim 1-7, it is characterised in that described anti-
It is toluene to answer matrix；The substitution product of the benzene substituted-phenyl α hydrogen is diphenyl-methane.
9. according to the compounds process for production thereof of any benzene substituted-phenyl α hydrogen of claim 1-7, it is characterised in that described anti-
It is 2- benzyloxies-N, N- dimethyl amine to answer matrix；The substitution product of the benzene substituted-phenyl α hydrogen is diphenhydramine.
10. the compounds process for production thereof of benzene substituted-phenyl α hydrogen is stated according to claim 9, it is characterised in that first by benzene sea
Lamine is dissolved in ethanol solution, the addition of the ethanol solution, in terms of molfraction, for 30-80 times of diphenhydramine；Then
Dry hydrogen chloride gas is passed through to saturation；0.5-5 hours are stirred at room temperature afterwards；Solvent is finally removed, obtains hydrochloric acid benzene
Extra large Lamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710806731.9A CN107522624A (en) | 2017-09-08 | 2017-09-08 | A kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710806731.9A CN107522624A (en) | 2017-09-08 | 2017-09-08 | A kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107522624A true CN107522624A (en) | 2017-12-29 |
Family
ID=60736480
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710806731.9A Withdrawn CN107522624A (en) | 2017-09-08 | 2017-09-08 | A kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107522624A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106146316A (en) * | 2015-04-09 | 2016-11-23 | 中国科学院化学研究所 | A kind of preparation method of 1,2-diaryl ethylenediamines compound |
| CN107673945A (en) * | 2017-09-27 | 2018-02-09 | 南华大学 | A kind of preparation method of toluene benzyl position phenyl-substituted compound |
-
2017
- 2017-09-08 CN CN201710806731.9A patent/CN107522624A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106146316A (en) * | 2015-04-09 | 2016-11-23 | 中国科学院化学研究所 | A kind of preparation method of 1,2-diaryl ethylenediamines compound |
| CN107673945A (en) * | 2017-09-27 | 2018-02-09 | 南华大学 | A kind of preparation method of toluene benzyl position phenyl-substituted compound |
Non-Patent Citations (2)
| Title |
|---|
| VASILOPOULOS, ARISTIDIS 等: "Feedstocks to Pharmacophores: Cu-Catalyzed Oxidative Arylation of Inexpensive Alkylarenes Enabling Direct Access to Diarylalkanes", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| 王池雅: "二苯甲烷合成研究进展", 《轻工科技》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zi et al. | Highly enantioselective hydroaminoalkylation of secondary amines catalyzed by group 5 metal amides with chiral biarylamidate ligands | |
| Zhou et al. | Functionalized IRMOF-3 as efficient heterogeneous catalyst for the synthesis of cyclic carbonates | |
| Liu et al. | Ionothermal synthesis of zirconium phosphates and their catalytic behavior in the selective oxidation of cyclohexane | |
| CN104245640B (en) | The four of ethene gather | |
| Choi et al. | Three-dimensional cobalt (II) and cadmium (II) MOFs containing 1, 4-naphthalenedicarboxylate: Catalytic activity of Cd-MOF | |
| JP2013503935A5 (en) | ||
| IE48062B1 (en) | Process for the production of magnesium hydrides | |
| Chai et al. | A novel chiral yttrium complex with a tridentate linked amido-indenyl ligand for intramolecular hydroamination | |
| TW201336856A (en) | Method of reducing a halosilane compound in a microreactor | |
| Ge et al. | Novel transition bimetal–organic frameworks: recyclable catalyst for the oxidative coupling of primary amines to imines at mild conditions | |
| Tan et al. | Ionothermal synthesis, crystal structure, and properties of an anionic two-dimensional cadmium metal organic framework based on paddle wheel-like cluster | |
| Dhankhar et al. | Construction of 3D lanthanide based MOFs with pores decorated with basic imidazole groups for selective capture and chemical fixation of CO 2 | |
| Martínez-Olid et al. | Magnetically recoverable catalysts based on mono-or bis-(NHC) complexes of palladium for the Suzuki–Miyaura reaction in aqueous media: two NHC–Pd linkages are better than one | |
| Peng et al. | Syntheses, structures and photoluminescence of Ln (III)–Cu (I) coordination polymers based on benzimidazole-5-carboxylate and oxalate ligands | |
| US20210284661A1 (en) | Mechanochemical synthesis of metal-organic frameworks for molecular sieving and compositions and methods of use thereof | |
| WO1995002567A1 (en) | Catalytic asymmetric reduction of trisubstituted olefins and enamines | |
| US11890602B2 (en) | Application of the ionic iron (III) complex as catalyst in preparation of benzylamine compound | |
| Wang et al. | Rapid and HF-free synthesis of MIL-100 (Cr) via steam-assisted method | |
| CN104557468B (en) | Method for phenol hydroxylation | |
| CN107522624A (en) | A kind of compounds process for production thereof of benzene substituted-phenyl α hydrogen | |
| Zhou et al. | Syntheses of supramolecular CuCN complexes by decomposing CuSCN: a general route to CuCN coordination polymers? | |
| Kitschke et al. | From a Germylene to an “Inorganic Adamantane”:[{Ge4 (μ‐O) 2 (μ‐OH) 4}{W (CO) 5} 4]· 4THF | |
| Zi et al. | Lanthanide and group 4 metal complexes with new chiral biaryl-based NNO-donor ligands | |
| CN107673945A (en) | A kind of preparation method of toluene benzyl position phenyl-substituted compound | |
| CN110204580A (en) | The nickelous imine composition of the nickeliferous dual bond structure of nitrogen and its preparation and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20171229 |