CN113620821A - Preparation method of hordenine hydrochloride - Google Patents
Preparation method of hordenine hydrochloride Download PDFInfo
- Publication number
- CN113620821A CN113620821A CN202111020578.XA CN202111020578A CN113620821A CN 113620821 A CN113620821 A CN 113620821A CN 202111020578 A CN202111020578 A CN 202111020578A CN 113620821 A CN113620821 A CN 113620821A
- Authority
- CN
- China
- Prior art keywords
- solution
- hordenine
- dimethylamine
- reaction
- ethanol
- 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.)
- Pending
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- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- KUBCEEMXQZUPDQ-UHFFFAOYSA-N hordenine hydrochloride Natural products CN(C)CCC1=CC=C(O)C=C1 KUBCEEMXQZUPDQ-UHFFFAOYSA-N 0.000 title claims description 175
- KIZRJFIRFPIRFS-UHFFFAOYSA-N 4-[2-(dimethylamino)ethyl]phenol;hydron;chloride Chemical compound Cl.CN(C)CCC1=CC=C(O)C=C1 KIZRJFIRFPIRFS-UHFFFAOYSA-N 0.000 title claims description 32
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims abstract description 175
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 158
- 238000006243 chemical reaction Methods 0.000 claims abstract description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 66
- 241000209219 Hordeum Species 0.000 claims abstract description 58
- 235000007340 Hordeum vulgare Nutrition 0.000 claims abstract description 58
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 claims abstract description 56
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 49
- DYYVTFCYVZEQDG-UHFFFAOYSA-N 4-(2-bromoethyl)phenol Chemical compound OC1=CC=C(CCBr)C=C1 DYYVTFCYVZEQDG-UHFFFAOYSA-N 0.000 claims abstract description 48
- 239000003513 alkali Substances 0.000 claims abstract description 40
- 238000005576 amination reaction Methods 0.000 claims abstract description 37
- 239000002994 raw material Substances 0.000 claims abstract description 23
- 238000003756 stirring Methods 0.000 claims abstract description 17
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- 229940071490 hordenine Drugs 0.000 claims description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 28
- -1 alkali metal cation compound Chemical class 0.000 claims description 26
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- 238000001914 filtration Methods 0.000 claims description 6
- 150000003842 bromide salts Chemical class 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 5
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 5
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- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000003061 melanogenesis Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- YVUZUKYBUMROPQ-UHFFFAOYSA-N mercury zinc Chemical compound [Zn].[Hg] YVUZUKYBUMROPQ-UHFFFAOYSA-N 0.000 description 1
- XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- UCQWVIYMRZFMBM-UHFFFAOYSA-N n,n-dimethyl-2-(4-nitrophenyl)acetamide Chemical compound CN(C)C(=O)CC1=CC=C([N+]([O-])=O)C=C1 UCQWVIYMRZFMBM-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229960000808 netilmicin Drugs 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- CHNLPLHJUPMEOI-UHFFFAOYSA-N oxolane;trifluoroborane Chemical compound FB(F)F.C1CCOC1 CHNLPLHJUPMEOI-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 208000010916 pituitary tumor Diseases 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 230000003658 preventing hair loss Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 150000003839 salts Chemical group 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Images
Classifications
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- 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
- C07C213/04—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reaction of ammonia or amines with olefin oxides or halohydrins
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of barley malt alkali hydrochloride, which comprises the steps of adding ethanol into 4- (2-bromoethyl) phenol serving as a raw material to prepare a solution, dropwise adding the solution and an excessive dimethylamine solution, stirring at a low temperature, and carrying out amination reaction to obtain barley malt alkali hydrobromide. Proper excessive dimethylamine is adopted, so that the quaternization side reaction is effectively inhibited, the solvent dispersion effect is exerted, the contact reaction chance of a barley malt alkali product generated by the first reaction and 4- (2-bromoethyl) phenol added later is greatly reduced, the higher product yield can be kept, and the lower preparation cost can be realized; adding 4- (2-bromoethyl) phenol into ethanol to prepare a dilute solution of ethanol, adding the dilute solution of ethanol into a dimethylamine solution in a dropwise manner, improving the dispersion degree of the 4- (2-bromoethyl) phenol in a reaction system, and inhibiting a quaternization side reaction; the amination reaction is stirred at a low temperature of 10-25 ℃, so that the occurrence of quaternization side reaction is inhibited, and a better reaction effect is achieved.
Description
Technical Field
The invention relates to the technical field of synthesis and preparation of barley malt alkali, in particular to a preparation method of barley malt alkali hydrochloride.
Background
Hordenine [ also known as barley amine; hordenine; anhaline, Eremursine, Peyocacine; international union nomenclature: 4- [2- (dimethyllamino) ethyl ] phenol; 4- (2-dimethylaminoethyl) phenol (structural formula IV); CAS: 539-15-1; the molecular formula is as follows: C10H15 NO; molecular weight: 165.24, respectively; white rhombic prism crystals (ethanol or benzene-petroleum ether) and needle crystals (water) with melting point of 117-118 ℃, boiling point of 173 ℃ (11mmHg) and sublimation temperature of 140-150 ℃. It is very soluble in ethanol, chloroform and diethyl ether, 7g in 1000ml water, slightly soluble in benzene, toluene and xylene, and hardly soluble in petroleum ether. Can act on adrenergic receptor, has effects of relaxing bronchial smooth muscle, contracting blood vessel, vasopression, increasing blood pressure and exciting center, can be used for relieving bronchitis and bronchial asthma and enhancing uterine tension and movement, and has dose-effect; meanwhile, the protective effect of radioactive damage is achieved; can inhibit melanogenesis by inhibiting cAMP production; the traditional Chinese medicine composition or related traditional Chinese medicine compound is usually clinically used for treating the hypogalactia of women or treating the hyperprolactinemia, and has remarkable curative effect and no side effect.
Reference documents: the inhibition effect of the hordenine on prolactin secretion of the rat with hyperprolactinemia is realized. [ Proprietary Chinese medicine ] 2018 Vol.40 No. 11P 2386-2389: the application of the hordenine in preparing the medicine for treating pituitary tumor is disclosed. The inventor finds that the hordenine can play a drug effect role in treating prolactin adenoma and adrenocorticotropic hormone adenoma by inhibiting a TLR 4/NF-kB/MAPK signal path, solves the problem of drug shortage of patients suffering from the prolactin adenoma and the adrenocorticotropic hormone adenoma, and discloses CN110151742A in Chinese patent publication. The application of the barley malt alkali in preparing the hypoglycemic medicament can obviously reduce fasting blood sugar and postprandial blood sugar level by intragastric administration of the barley malt alkali to db/db diabetic mice. For streptozotocin-induced diabetic mice, the administration of hordenine in combination with intraperitoneal injection of insulin through intragastric administration obviously reduces the fasting blood glucose level. Therefore, the use of the barley malt alkali can achieve a remarkable blood sugar reducing effect, and the Chinese patent publication CN 108159030A. The anti-infection pharmaceutical use of the barley malt alkali or the combined antibiotics thereof discloses a new use of the natural product barley malt alkali, in particular to the application of the compound barley malt alkali in preparing the medicines for preventing and treating bacterial infection, which is mainly shown in the following steps: the barley malt alkaloid can obviously inhibit the synthesis of signal molecules regulated by quorum sensing, the barley malt alkaloid can obviously inhibit the expression of virulence factors regulated by quorum sensing, and the barley malt alkaloid can obviously inhibit the expression of quorum sensing related genes. In addition, the combination of the barley malt alkaloid and the antibiotic netilmicin can obviously inhibit the generation of the biofilm, can obviously destroy the formed biofilm, and is expected to become a novel anti-infective agent for preventing and treating bacterial infection, and Chinese patent publication CN 107929742A. The application of the hordenine and the hydrochloride in the aspects of hair loss prevention agents (US 20210030787, CN 201980055668.7), weight loss agents (US 20040185069), sobering agents (US 20200305487), sport supplements (US 20200306187), functional food additives (US 20120120128800, 20020192316, US 20110281808) and the like is being developed, reported and applied.
In nature, hordenine is present in roots of germinated barley seeds, roots of Desmodiumgangeticum (L.) DC, which is a leguminous plant, stems of desmodium begani (d.tiliefolium g.don), heartwood of pseudo-wood beans (d.cephalotes Wall), and the like. Abroad, it is mainly found in the palm of Paott (Lophora williamsii), the holy Peel
Radix et caulis Opuntiae Dillenii (Echinopsis Pachanoi) and radix et caulis Opuntiae Dillenii (Echinopsis Peruviana), and cornu rhinocerotis Stapelia
In gigantea.
However, the extraction and separation from the plants are relatively difficult, the purity of the product is not high, and the use requirement cannot be met.
Hordenine is not conducive to long-term storage, and is therefore usually produced as Hordenine hydrochloride (Hordenine hydrochloride;
international union nomenclature: 4- [2- (dimethyllamino) ethyl ] phenol, hydrochloride. CAS: 6027-23-2; molecular formula
C10h15no. hcl; molecular weight 201.69) for ease of storage and transportation.
The hordenine can be conveniently obtained by adding base to free hordenine hydrochloride.
The chemical synthesis preparation method of the barley malt alkali hydrochloride mainly comprises the following steps:
firstly, alcohol solution of alpha-chloro-4-methoxyacetophenone and dimethylamine is condensed and subjected to deprotection to obtain alpha-dimethylamino-4-hydroxyacetophenone, and then carbonyl is reduced into methylene under the action of red phosphorus/hydroiodic acid to prepare the compound; the raw materials of the route are not easy to obtain
The step length is long, and the reduction yield is low; the total yield is 10 percent, and the industrial application value is not high. (Voswinckel H.New synthesis of hordenine [ J ]. Ber Dtsch Chem Ges, 1912, 45 (1): P1004-1006.)
Beta-phenyl ethyl amine derivatives.1 Tertiary and Quaternary Salts; is prepared by taking p-alkoxy benzaldehyde as a raw material and carrying out condensation, hydroxylamination, decarboxylation methylation and dealkylation; long route, high cost and no industrial application value.
Johannes S.Buck,Richard Baltzly,and Walter S.Ide Journal of the American Chemical Society1938,60,8,1789-1792(Article) Publication Date (Print):August 1, 1938
③ A New Synthesis of Hordenine and Other p-dialkyl amidophenols and Some of Their Derivatives (New Synthesis of barley malt base and Other p-dialkyl amidoethylphenols and Derivatives); the raw materials are not easy to obtain, and the yield is low.
Chao-Shing Cheng, Claus Ferber, Raymond I. Bashford Jr., and Gerald F. Grillot Journal of the American Chemical Society 1951, 73, 9, 4081-4084 (Article)
Publication Date (Print):September 1, 1951
And fourthly, the tetrahydrofuran solution of 2-bromo-1- (4-methoxyphenyl) ethane and dimethylamine is used for tube sealing condensation and BBr3 demethoxylation protection, and the total yield is about 40%. The disadvantage of the route is that the preparation process of the 2-bromo-1- (4-methoxyphenyl) ethane is complex, a pressure reaction kettle is used for the pipe sealing operation, and the equipment cost is increased; BBr3 has high irritation, increased operation difficulty, more three wastes and high production cost. (Wosolski R, Hailes H, number M, et a 1. sub-sized phenols and related compounds, and the prediction, pharmaceutical compositions and use for modulation
PKB activity：WO，2006097744[P]．2006—09-21．）
The p-hydroxyphenylethylamine is reacted with paraformaldehyde under the action of methanol and sodium triacetoxyborohydride, the method has the advantages of short steps, good conversion rate, easy polymerization reaction, high price of sodium triacetoxyborohydride, high raw material price, more three wastes and high cost. (Swanson DM, Wilson SJ, Boggs JD, et a 1. Aplysamine-1 and related analytes histamines H3 receptor antagnostists [ J ]. Bioorg Med Chem Lett, 2006, 16 (4): 897-
Sixthly, the p-hydroxyacetophenone is used as the raw material, firstly the bromination is carried out to obtain the a-bromo-p-hydroxyacetophenone, then the a-bromo-p-hydroxyacetophenone is condensed with the dimethylamine aqueous solution, and finally the condensation is carried out
The reduction of carbonyl by zinc amalgam produced hordenine with a total yield of about 49%. By-product treatment of large amounts of hydrobromic acid produced by bromination with elemental bromine
The method has the defects of difficult treatment, extremely high treatment cost, difficult mercury removal by product purification and difficult industrial production due to the generation of a large amount of acidic mercury-zinc wastes by zinc amalgam reduction. ([ China journal of medical industry) ] Synthesis of hordenine "Wangkai et al 2011, 42 (8), P574-576)
Seventhly, methyl p-hydroxyphenylacetate and dimethylamine are used as raw materials, and the barley malt alkali hydrochloride is prepared through amination and reduction, wherein the total yield is about 65%; however, a large amount of sodium borohydride and boron trifluoride tetrahydrofuran with high price are used as a reducing agent and a catalyst, and meanwhile, a large amount of byproducts and waste materials are generated, the three wastes treatment cost is high, and the production cost is high. (Chinese patent publication No. CN106916073A, publication No. 2017.07.04)
Other synthetic methods references:
journal of the American Chemical Society, vol.73, p. 4081,4082; 4-methoxy phenethyl alcohol is taken as a raw material, Justus Liebigs Annalen der Chemie, vol.431, p.213 chem, Zentralbl, vol.94, # II p.403;
with 2- (4-methoxyphenyl) -N, N-dimethylethanethioamide and
n, N-dimethyl-2- (4-nitrophenyl) acetamide as raw material
Archiv der Pharmazie (Weinheim, Germany), vol. 271, p. 439,445 Journal of the American Chemical Society, vol. 60, p. 1789,1790
Takes p-methoxybenzyl acetonitrile, N, N-dimethyl-4-methoxyphenylethyl amine as raw material
DE 233069; fortschr. Tererfarbenfabr. Verw. Industriezweight, vol. 10, p. 1229; reversely synthesizing DE396453 by using candeliline hydrochloride as a raw material; fortschr. Tererfarbenfabr. Verw. Industriezweight, vol. 14, p. 401; 4- (2-dimethylaminoethyl) aniline is used as a raw material.
At present, the preparation methods have no industrial production value.
With the continuous development of new applications of the hordenine, the market demand for the hordenine hydrochloride is greatly increased, and an efficient synthesis preparation method which has the advantages of easily available raw materials, mild reaction conditions, high product yield, relatively low production cost, less three wastes, simple and convenient operation and easy cleaning industrial production is urgently needed to be developed.
Disclosure of Invention
In order to overcome the technical problems in the background art, the invention provides a preparation method of hordenine hydrochloride.
The technical scheme adopted by the invention for solving the technical problems is as follows:
a method for preparing hordenine hydrochloride comprises the steps of dissolving 4- (2-bromoethyl) phenol serving as a raw material in ethanol to obtain a solution, dripping the solution into a dimethylamine solution, and stirring at a low temperature to carry out amination reaction to obtain hordenine hydrobromide;
removing the dryness of the barley malt alkali hydrobromide, adding ethanol for dissolving to prepare a solution, and adding the solution and an aqueous solution of an alkali metal cation compound into the solution
Performing alkalization reaction to obtain hordenine and alkali metal bromide, adding hydrochloric acid to neutralize hordenine to obtain hordenine hydrochloride, removing water, adding anhydrous ethanol to dissolve the hordenine hydrochloride therein, filtering to separate alkali metal bromide, and purifying to obtain the final product
To a hordenine hydrochloride product.
Further, the preparation method of the hordenine hydrochloride comprises the following specific steps:
A. amination reaction: dissolving 4- (2-bromoethyl) phenol serving as a raw material in ethanol to prepare a solution containing 15-30 wt% of 4- (2-bromoethyl) phenol, and dropwise adding the solution into 30-40 wt% of dimethylamine solution; the molar ratio of the 4- (2-bromoethyl) phenol to the dimethylamine is 1: 7-20; stirring at the temperature of 0-30 ℃ for amination reaction for 12-24 hours, and distilling out dimethylamine, ethanol and water to obtain barley malt alkali hydrobromide;
wherein the structural formula of the 4- (2-bromoethyl) phenol is as follows:
the Chinese alias of 4- (2-bromoethyl) phenol is p-hydroxyphenylethyl bromide;
english name: 4- (2-Bromoethyl) phenol;
international union nomenclature: 4- (2-bromoethyl) phenol;
english alias: 4-Hydroxy-1- (2-bromoethyl) bezene, 4-hydroxyphenyl ethane nitrile, 4-
(2-BROMOETHYL)PHENOL；
CAS number 14140-15-9; the molecular formula is C8H9 BrO; molecular weight 201.063;
physical and chemical properties: the density is 1.5 +/-0.1 g/cm 3; boiling point 276.5 + -15.0 deg.C (760 mmHg);
melting point 88-92 deg.C (lit.); flash point 121.1 +/-20.4 ℃; refractive index 1.593; vapor pressure 0.00283mmHg (25 deg.C); the raw material is used as an important organic synthesis intermediate, particularly as a high-activity nucleophilic reaction substance, and can efficiently carry out reactions such as N-alkylation and the like to synthesize a plurality of useful compounds; the raw material can be conveniently purchased from the market and can also be synthesized by various methods.
The structural formula of the barley malt base hydrobromide is as follows:
the reaction formula is as follows:
B. hydrochloric acid reaction: dissolving the hordenine hydrobromide prepared in the step A in ethanol to prepare a solution containing 15-25 wt% of the hordenine hydrobromide, and mixing the solution with a saturated aqueous solution of an alkali metal cation compound at the temperature of 25-75 DEG C
Performing alkalization reaction to obtain hordenine and alkali metal bromide salt; adding hydrochloric acid to neutralize the barley malt base to obtain barley malt base hydrochloride; after ethanol and water are removed, absolute ethanol is added to dissolve the hordenine hydrochloride, then alkali metal bromide is separated out by filtration, activated carbon is added for decolorization, and finally, a hordenine hydrochloride product is prepared by crystallization or recrystallization;
the structural formula of the hordenine is as follows:
the structural formula of the barley malt base hydrochloride is as follows:
the alkalization reaction formula is as follows:
the hydrochlorination reaction formula is as follows:
in the alkalization reaction formula: m＋N－ Is an alkali metal cation compound; m＋Is an alkali metal cation K＋Or Na＋， N－Is an anion OH－1、CO3 －2And HCO3 －2One kind of (1).
Because the chemical structure of the barley malt alkali hydrobromide is actually an inorganic acid salt of organic tertiary amine; the reaction of 4- (2-bromoethyl) phenol, an active haloalkane nucleophile, with dimethylamine to form the hydrobromide salt of hordenine is well known to those skilled in the art as a general technique for the synthesis of higher amines (referred to herein as hordenine, a "tertiary amine") from lower amines (referred to herein as dimethylamine, a "secondary amine"); is a typical reaction of alkyl halides-nucleophilic substitution reactions, also commonly called ammonolysis or amination reactions of alkyl halides; for active alkyl halides such as 4- (2-bromoethyl) phenol, the reaction is easy to carry out and the conversion rate is high; the only disadvantages of this reaction are: if the reaction conditions (particularly the mixture ratio of alkyl halide to amine) are not proper, quaternization side reaction can occur to generate a quaternary ammonium salt byproduct of dimethyl di-p-hydroxyphenylethyl ammonium bromide;
2
+ 
common techniques for inhibiting the quaternization side reactions include: the excessive amine is used, the side reaction speed is slowed down, the solvent dispersion effect is exerted, and the reaction temperature which is beneficial to the main reaction is controlled; in the reaction, when the molar ratio of 4- (2-bromoethyl) phenol to dimethylamine is more than 1:5, the occurrence of quaternization side reaction can be effectively inhibited, and the yield of the product reaches 90 percent; when the mixture ratio is increased to 1:7mol, the product yield reaches 94 percent; when the mixture ratio is increased to 1:15mol, the product yield is more than 95 percent; if the ratio is excessively large, the yield of the product is slowly increased, and the equipment is too large, so that the preparation cost is undesirably high.
In the method, proper excess dimethylamine is used, and the molar ratio of 4- (2-bromoethyl) phenol to dimethylamine is 1: 7-20. Simultaneously, the solvent dispersion effect is exerted, and a great deal of dilution is realized, so that the barley malt alkali product generated firstly and the 4-substituted ketone added later are greatly reduced
A contact reaction opportunity of (2-bromoethyl) phenol; higher product yields can be maintained while achieving lower manufacturing costs.
Further preferably, in the amination reaction of the step A, the molar ratio of the 4- (2-bromoethyl) phenol to the dimethylamine is 1: 10-15, and the content of the dimethylamine in the dimethylamine solution is 30-40% (by weight). Proper excessive dimethylamine is used for inhibiting the quaternization side reaction, simultaneously the solvent dispersion effect is exerted, and a large amount of dilution is carried out, so that the contact reaction chance of a barley malt alkali product generated firstly and 4- (2-bromoethyl) phenol added later is greatly reduced; higher product yields can be maintained while achieving lower manufacturing costs.
Preferably, in the step a, ethanol is added into the 4- (2-bromoethyl) phenol to prepare a solution containing 20-25 wt% of 4- (2-bromoethyl) phenol, the solution is added into the dimethylamine solution in a dropwise manner, and the mixture is stirred at the temperature of 10-25 ℃ to carry out amination reaction for 15-20 hours. The dispersity of 4- (2-bromoethyl) phenol in the reaction can be further improved, so that the occurrence of quaternization side reaction is reduced; the reaction temperature is controlled to be 10-25 ℃, and the mixture is stirred at a low temperature for amination reaction for 15-20 hours, so that the occurrence of quaternization side reaction can be further reduced, and the yield of the product of the hordenine hydrobromide is improved. The method is based on the characteristics of amination reaction (the higher the reaction temperature is, the more easily the polyalkylation reaction occurs, namely the quaternization reaction), and in order to inhibit the quaternization side reaction, a convenient and effective means of reducing the reaction temperature to slow down the side reaction speed is adopted; when the reaction temperature is lower than 0 ℃, the reaction is too slow; when the reaction temperature is higher than 30 ℃, dimethylamine escapes from the reaction system to influence the yield; the reaction temperature is controlled to be 10-25 ℃, so that the quaternization side reaction can be effectively inhibited, the main reaction time is not too long, and a good amination reaction effect can be achieved.
Preferably, in the step a, the dimethylamine solution is: one or two of dimethylamine water solution and dimethylamine ethanol solution. Because the amination reaction speed is high, the solvent amount of a reaction system is also high, and water or alcohol brought by the dimethylamine raw material is an excellent solvent of the hordenine hydrobromide, the generated hordenine hydrobromide can be quickly dissolved
In the reaction system, the side reaction is inhibited; the amination reaction can be well performed no matter water or ethanol or binary mixture of water and alcohol with any concentration.
Preferably, in the step B, the barley malt alkali hydrobromide prepared in the step A is added with ethanol to prepare a solution containing 20-40 wt% of the barley malt alkali hydrobromide, and the solution and a saturated aqueous solution of an alkali metal cation compound are subjected to an alkalization reaction at a temperature of 40-60 ℃ to obtain the barley malt alkali and an alkali metal bromide.
The reaction of organic amine salt and inorganic alkali solution with the alkaline strength higher than that of organic amine, wherein the reaction for dissociating the organic amine and generating the inorganic salt is an alkalization reaction which is a basic reaction of organic synthesis, is equivalent to an acid-base neutralization reaction and is commonly used for purification of the organic amine and conversion of the organic acid salt; wherein the alkaline strength of potassium bicarbonate, sodium bicarbonate, potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide is greater than that of the hordenine; the concentrated solution (10-50%) and the saturated solution of the alkali can be subjected to an alkalization reaction with the barley malt alkali hydrobromide to free out the barley malt alkali; therefore, in the step B, based on the high melting point and water-insoluble property of the hordenine, the generated hordenine is dissolved in a mixed system of ethanol and water by using an alcohol-water mixed reaction solvent, so that the alkalization reaction is more complete. The time of the alkalization reaction is longer when the temperature is lower than 25 ℃, phenolic hydroxyl can generate phenate when the temperature is higher than 75 ℃, the alkalization reaction is carried out at the temperature of 25-75 ℃, a good alkalization effect can be obtained, and particularly, the reaction time is short and the alkalization is complete when the reaction is carried out at the temperature of 40-60 ℃.
Preferably, in the alkalization reaction in the step B, the molar ratio of the hordenine hydrobromide to the alkali metal cation in the alkali metal cation compound is 1: 1.05-1.15. Can effectively avoid incomplete dissociation of the barley malt alkali and reduce the ineffective dosage of alkali metal cation compounds.
Preferably, in the step B, hydrochloric acid is added to neutralize the hordenine, and the molar ratio of the hordenine to hydrogen chloride in the hydrochloric acid is 1: 1.10-1.30. Can realize complete neutralization reaction of hydrochloric acid and reduce the ineffective dosage of hydrochloric acid.
In the amination reaction of the step A, after the amination reaction is finished, excessive dimethylamine solution is subjected to first distillation to obtain dimethylamine gas, water or ethanol or a mixed solution of ethanol and water is adopted as an absorption liquid, and the dimethylamine gas is absorbed until the content of the dimethylamine is 30-40 percent (by weight) and then is recycled for the amination reaction of the step A; and secondly, distilling the ethanol mixed solution containing water and residual dimethylamine again to be used as the absorption liquid of the dimethylamine gas obtained by the first distillation for recycling.
In the second recovery mode, in the amination reaction of the step A, after the excess dimethylamine solution is subjected to amination reaction, liquefied dimethylamine is introduced to absorb the content of dimethylamine to 30-40% (by weight), and the dimethylamine solution is recycled for the amination reaction of the step A.
In the invention, two reactant recovery methods can be adopted for the excessive dimethylamine after the amination reaction in the step A, so that the discharge of wastes can be greatly reduced, and the economic benefit of the preparation process is improved.
The invention has the beneficial effects that: in the step A, 4- (2-bromoethyl) phenol is used as a raw material, ethanol is added to prepare a solution, and the solution is dropwise added into an excessive dimethylamine solution and stirred at a lower temperature to carry out amination reaction to obtain the hordenine hydrobromide. Proper excessive dimethylamine is adopted, so that the quaternization side reaction is effectively inhibited, the solvent dispersion effect is exerted, the contact reaction chance of a barley malt alkali product generated firstly and 4- (2-bromoethyl) phenol added later is greatly reduced, the higher product yield can be kept, and the lower preparation cost can be realized; adding 4- (2-bromoethyl) phenol into ethanol to prepare a dilute solution of ethanol, adding the dilute solution of ethanol into a dimethylamine solution in a dropwise manner, improving the dispersion degree of the 4- (2-bromoethyl) phenol in a reaction system, and inhibiting a quaternization side reaction; stirring at a lower temperature of 10-25 ℃ for amination reaction, further inhibiting the occurrence of quaternization side reaction, and achieving a better reaction effect.
In step B, the hordenine hydrobromide is added to ethanol according to the high melting point and water-insoluble properties of the hordenine
Making into solution, alkalifying with saturated solution of alkali metal cation compound to dissolve the produced hordenine in ethanol and water
In the mixed solution system, the alkalization reaction is more complete; the alkalization reaction is carried out at the temperature of 25-75 ℃, so that the technical effects of short reaction time and complete alkalization are realized; the molar ratio of the barley malt alkali hydrobromide to the alkali metal cations in the alkali metal cation compound is 1: 1.05-1.15, so that incomplete dissociation of barley malt alkali can be effectively avoided, and the ineffective reaction dosage of the alkali metal cation compound is reduced.
And B, adding hydrochloric acid to neutralize the hordenine, wherein the molar ratio of the hordenine to hydrogen chloride in the hydrochloric acid is 1: 1.10-1.30. Can realize complete neutralization reaction of hydrochloric acid and reduce the ineffective dosage of hydrochloric acid.
In the step A, for the utilization of excessive dimethylamine solution after amination reaction, the invention also provides two simple recycling methods, which can greatly reduce the discharge of waste, improve the economic benefit of the preparation process and realize better environmental protection effect.
Drawings
FIG. 1 is a schematic diagram of the preparation method of the present invention.
Detailed Description
The following examples are provided to illustrate a method for preparing hordenine hydrochloride according to the present invention, in which 4- (2-bromoethyl) phenol is used as a raw material, and ethanol is added to dissolve the raw material into a solution, and then the solution is added dropwise to a dimethylamine solution, and the mixture is stirred at a low temperature to perform an amination reaction, thereby obtaining hordenine hydrobromide;
removing the dryness of the hordenine hydrobromide, adding ethanol to dissolve the hordenine hydrobromide to prepare a solution, carrying out an alkalization reaction with an alkali metal cation compound aqueous solution to obtain hordenine and alkali metal bromide salt, adding hydrochloric acid to neutralize the hordenine to obtain hordenine hydrochloride, removing water, adding absolute ethanol to dissolve the hordenine hydrochloride, filtering to separate out the alkali metal bromide salt, and purifying to obtain the hordenine hydrochloride product. The preparation method of the invention has the technical process as shown in figure 1.
Example 1:
preparation of hordenine hydrobromide:
1970 g of dimethylamine absolute ethanol solution industrial product (containing 17.5mol of dimethylamine) with the weight percentage of 40 percent is added into a circular four-port glass reaction bottle with the capacity of 5 liters and provided with a reflux ice brine condenser, a thermometer, a dropping bottle and a stirrer, and the reaction bottle is placed in an ice water bath; stirring and cooling to 0 ℃, slowly dropping a mixed solution consisting of 610 g of 4- (2-bromoethyl) phenol (the content is 99 percent, 2.5mol) and 1420 g of absolute ethyl alcohol by a dropping bottle; and keeping the temperature of the reaction solution at 0-5 ℃ in the dropping process. After the dropwise addition, removing the ice water bath, and stirring and reacting at normal temperature for 12 hours; then, heating the mixture to 75 ℃ in a water bath, distilling out excessive dimethylamine gas for the first time, and absorbing the excessive dimethylamine gas by using 1400 g of absolute ethyl alcohol which is cooled to 0-5 ℃ as an absorption liquid; the ethanol was again distilled off a second time until crystallization occurred, then dried under vacuum and cooled to room temperature to give 582 g of light yellow hordenine hydrobromide in 95% yield based on 4- (2-bromoethyl) phenol.
2200 g of anhydrous ethanol dimethylamine solution is obtained after the first distillation and absorption, wherein the content of dimethylamine is 30.2 percent (weight), and the dimethylamine solution can be recycled for amination reaction; the ethanol mixed solution containing low-concentration dimethylamine is distilled again for the second time, and can be used for next distillation of dimethylamine gas absorption solution.
Example 2:
preparation of hordenine hydrobromide:
the procedure of example 1 was followed; except that 1970 g of an aqueous dimethylamine solution, 40% by weight, was used as a commercial product; after the dropwise adding is finished, heating the mixture to 15 ℃ in a water bath, and stirring the mixture for reacting for 18 hours at the reaction temperature of 15-20 ℃; then, the mixture was heated in a water bath to 75 ℃ to distill out excessive dimethylamine gas for the first time, and the ethanol mixture containing low concentration dimethylamine distilled out for the second time in example 1 was used as an absorption solution of dimethylamine gas; the ethanol was redistilled a second time until crystallization occurred to give 582 g of light yellow hordenine hydrobromide in 94.5% yield based on 4- (2-bromoethyl) phenol.
Wherein 2200 g of ethanol and water mixed solution containing low-concentration dimethylamine are obtained by the first distillation and absorption, wherein the content of the dimethylamine is 30 percent by weight; the mixed solution of water and ethanol containing low-concentration dimethylamine is distilled for the second time, and can be used for next distillation of dimethylamine gas absorption solution.
Example 3:
preparation of hordenine hydrobromide:
3500ml of 40% dimethylamine aqueous solution industrial product (3150 g, containing 28mol of dimethylamine) is added into a round four-mouth glass reaction bottle with the capacity of 5000ml, a reflux brine condenser, a thermometer, a dropping bottle and a stirrer, and the reaction bottle is placed in an ice water bath kettle; stirring and cooling to 0 ℃, and slowly dropwise adding a mixed solution consisting of 187 g of 4- (2-bromoethyl) phenol (the content is 99 percent and the mole is 0.93mol) and 1240 g of absolute ethyl alcohol through a dropping bottle; keeping the temperature of the reaction liquid at 0-5 ℃ in the dropping process; and after the dropwise addition is finished, removing the ice water bath, heating the water bath to 25 ℃ after the dropwise addition is finished, and stirring and reacting at the normal temperature of 25-30 ℃ for 12 hours. Then, heating in water bath to 90 ℃ instead, and evaporating excessive dimethylamine for the first time (using 1800 g of a mixed solution of water and ethanol containing low-concentration dimethylamine distilled for the second time in the example 2 cooled to 5-10 ℃ as an absorption solution for absorption); the water was again distilled off a second time until crystallization occurred, the water was again dried in vacuo and cooled to room temperature to give 224 g of light yellow hordenine hydrobromide in 97% yield based on 4- (2-bromoethyl) phenol.
Wherein, after the first distillation, 3000 g of an aqueous dimethylamine solution was obtained by absorption, the dimethylamine content being 39.8% by weight; and distilling the mixed solution of water and ethanol containing the low-concentration dimethylamine for the next batch of dimethylamine absorption solution.
Example 4:
preparation of hordenine hydrobromide:
the procedure of example 1 was followed; the difference is that: 800 g of the dimethylamine solutions recovered in the examples 1 and 2 and 1600 g of the dimethylamine solution recovered in the example 3 are added; a mixed solution composed of 201 g of 4- (2-bromoethyl) phenol (content: 99%, 1mol) and 570 g of ethanol was added; after the dropwise adding is finished, heating the mixture to 15 ℃ in a water bath, and controlling the reaction temperature to be 10-15 ℃ for reacting for 20 hours; this gave 240 g of light yellow hordenine hydrobromide in 97.2% yield based on 4- (2-bromoethyl) phenol.
Example 5:
preparation of hordenine hydrochloride:
adding 582 g of the barley malt base hydrobromide prepared in example 1 (containing 2.35mol of the barley malt base hydrobromide) and 845 g of ethanol into a four-port glass reactor with a capacity of 3 liters and a stirring thermometer, and dropwise adding 461 g of 30% potassium hydroxide solution into the four-port glass reactor by a dropping bottle under stirring, wherein the dropwise addition is finished; continuously stirring at the temperature of 25-30 ℃ for carrying out an alkalization reaction for 1 hour to generate hordenine and potassium bromide; then, 255 g of 37 percent (weight) hydrochloric acid is dropwise added into the mixture through a dropping bottle, and the temperature is controlled to be 25-30 ℃ after the dropwise addition, the mixture is continuously stirred for neutralization reaction for 2 hours to generate a light yellow solution of the barley malt alkali hydrochloride; heating, distilling off ethanol under stirring, transferring into a rotary vacuum evaporator, and evaporating to remove water to obtain light yellow powder; then, 800 g of absolute ethanol is added to stir and dissolve the barley malt alkali hydrochloride, and insoluble potassium bromide is filtered out (the solution is washed 4 times by 50 ml of absolute ethanol each time); mixing the filtrate and washing liquid, adding 3 g of activated carbon powder, stirring and heating to reflux, decoloring, and filtering to obtain a transparent almost colorless solution; then, the reaction mixture was transferred to a rotary vacuum evaporator to evaporate the solvent to obtain 461 g of barley malt alkali hydrochloride as a white powder. The analytical purity is 99.3%; the yield was 96.7% based on the amount of barley malt base hydrobromide and 91.4% based on the total amount of 4- (2-bromoethyl) phenol.
Example 6:
preparation of hordenine hydrochloride:
the procedure of example 5 was followed; the difference is that: there were used solutions obtained by dissolving 585 g of the hordenine hydrobromide salt obtained in example 2 and 1300 g of ethanol; dropping 465 g of 30% sodium carbonate solution, reacting at the alkalization reaction temperature of 40-45 ℃ for 1.5 hours, and adding 270 g of hydrochloric acid to obtain 463 g of white powdery barley malt alkali hydrochloride. The analytical purity is 99.4%; the yield was 96.6% based on the amount of barley malt base hydrobromide and 91.8% based on the total amount of 4- (2-bromoethyl) phenol.
Example 7:
preparation of hordenine hydrochloride:
the procedure of example 5 was followed; the difference is that: the solution obtained by dissolving 240 g of the hordenine hydrobromide obtained in example 3 and 980 g of ethanol was used; adding 374 g of 30% potassium bicarbonate solution dropwise, reacting at the alkalization reaction temperature of 60-65 ℃ for 2 hours, and adding 117 g of hydrochloric acid and 1 g of activated carbon to obtain 179 g of white powdery barley malt alkali hydrochloride. The analytical purity was 99.4%, the yield was 97% based on the hordenine hydrobromide and the total yield was 94.1% based on 4- (2-bromoethyl) phenol.
Example 8:
preparation of hordenine hydrochloride:
the procedure of example 5 was followed; the difference is that: the solution obtained by dissolving 224 g of the hordenine hydrobromide obtained in example 4 and 900 g of ethanol was used; dropwise adding 110 g of 35% sodium hydroxide solution; carrying out an alkalization reaction at 60-65 ℃ for 2 hours; 108 g of hydrochloric acid and 1 g of activated carbon were added to obtain 179 g of barley malt base hydrochloride as a white powder. The analytical purity was 99.5%, the yield was 97% based on the hordenine hydrobromide and the total yield was 94.3% based on 4- (2-bromoethyl) phenol.
In this specification, the invention has been described with reference to specific embodiments thereof, but it will be apparent that various modifications can be made without departing from the scope of the invention. The description is thus to be regarded as illustrative instead of limiting.
Claims (10)
1. A preparation method of barley malt alkali hydrochloride is characterized in that 4- (2-bromoethyl) phenol is used as a raw material, ethanol is added to dissolve the 4- (2-bromoethyl) phenol into a solution, the solution is dripped into a dimethylamine solution, and the dimethylamine solution is stirred at low temperature to carry out amination reaction to obtain barley malt alkali hydrobromide;
removing the dryness of the hordenine hydrobromide, adding ethanol to dissolve the hordenine hydrobromide to prepare a solution, carrying out an alkalization reaction with an alkali metal cation compound aqueous solution to obtain hordenine and alkali metal bromide salt, adding hydrochloric acid to neutralize the hordenine to obtain hordenine hydrochloride, removing ethanol and water, adding absolute ethanol to dissolve the hordenine hydrochloride, filtering to separate the alkali metal bromide salt, and purifying to obtain the hordenine hydrochloride product.
2. The method for preparing the hydrochloride of the hordenine according to claim 1, which comprises the following steps:
A. amination reaction: dissolving 4- (2-bromoethyl) phenol serving as a raw material in ethanol to prepare a solution containing 15-30 wt% of 4- (2-bromoethyl) phenol, and dropwise adding the solution into 30-40 wt% of dimethylamine solution; the molar ratio of the 4- (2-bromoethyl) phenol to the dimethylamine is 1: 7-20; stirring at the temperature of 0-30 ℃ for amination reaction for 12-24 hours, and distilling out dimethylamine, ethanol and water to obtain barley malt alkali hydrobromide;
wherein the structural formula of the 4- (2-bromoethyl) phenol is as follows:
the structural formula of the barley malt base hydrobromide is as follows:
the reaction formula is as follows:
B. hydrochloric acid reaction: b, adding ethanol into the barley malt alkali hydrobromide prepared in the step A for dissolving, preparing a solution containing 15-25% by weight of the barley malt alkali hydrobromide, and carrying out an alkalization reaction with a saturated aqueous solution of an alkali metal cation compound at the temperature of 25-75 ℃ to obtain barley malt alkali and an alkali metal bromide; adding hydrochloric acid to neutralize the barley malt base to obtain barley malt base hydrochloride; after ethanol and water are removed, absolute ethanol is added to dissolve the hordenine hydrochloride, then alkali metal bromide is separated out by filtration, activated carbon is added for decolorization, and finally, a hordenine hydrochloride product is prepared by crystallization or recrystallization;
the structural formula of the hordenine is as follows:
the structural formula of the barley malt base hydrochloride is as follows:
the alkalization reaction formula is as follows:
the hydrochlorination reaction formula is as follows:
in the alkalization reaction formula: m＋N－Is an alkali metal cation compound; m＋Is an alkali metal cation K＋Or Na＋， N－ Is an anion OH－1、CO3 －2And HCO3 －2One kind of (1).
3. The method for preparing hordenine hydrochloride according to claim 2, wherein in the amination in the step A, the molar ratio of 4- (2-bromoethyl) phenol to dimethylamine is 1: 10-15; the content of dimethylamine in the dimethylamine solution is 30-40% (by weight).
4. The method according to claim 2, wherein in step A, the 4- (2-bromoethyl) phenol is added with ethanol to prepare a solution containing 20-25 wt% of 4- (2-bromoethyl) phenol, the solution is added dropwise to the dimethylamine solution, and the amination reaction is performed at 10-25 ℃ for 15-20 hours with stirring.
5. The method according to claim 2, wherein in the step A, the dimethylamine solution is: one or two of dimethylamine water solution and dimethylamine ethanol solution.
6. The method according to claim 2, wherein in step B, the hordenine hydrobromide obtained in step A is added with ethanol to prepare a solution containing 20-40 wt% of the hordenine hydrobromide, and the solution is subjected to an alkalization reaction with a saturated aqueous solution of an alkali metal cation compound at a temperature of 40-60 ℃ to obtain the hordenine and the alkali metal bromide.
7. The method for preparing hordenine hydrochloride according to claim 2, wherein in the alkalization reaction in the step B, the molar ratio of the hordenine hydrobromide to the alkali metal cation in the alkali metal cation compound is 1: 1.05-1.15.
8. The method for preparing hordenine hydrochloride according to claim 2, wherein in the step B, the hordenine is neutralized by adding hydrochloric acid, and the molar ratio of the hordenine to the hydrogen chloride in the hydrochloric acid is 1: 1.10-1.30.
9. The method for preparing hordenine hydrochloride according to claim 2, wherein in the amination reaction of step A, after the amination reaction is completed, an excessive dimethylamine solution is subjected to first distillation to obtain dimethylamine gas, and water or ethanol or a mixed solution of ethanol and water is used as an absorption solution, and the dimethylamine gas is absorbed until the content of dimethylamine is 30-40% (by weight), and then is recycled for the amination reaction of step A; and secondly, distilling the ethanol mixed solution containing water and residual dimethylamine again to be used as the absorption liquid of the dimethylamine gas obtained by the first distillation for recycling.
10. The method according to claim 2, wherein in the amination step A, excess dimethylamine solution is introduced into liquefied dimethylamine after the amination step is completed, and the liquefied dimethylamine is recycled for the amination step A after the dimethylamine solution absorbs 30-40 wt% of dimethylamine.
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