CN105503923A - Method for synthetizing isopropenyl boric acid ester - Google Patents
Method for synthetizing isopropenyl boric acid ester Download PDFInfo
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- CN105503923A CN105503923A CN201610011092.2A CN201610011092A CN105503923A CN 105503923 A CN105503923 A CN 105503923A CN 201610011092 A CN201610011092 A CN 201610011092A CN 105503923 A CN105503923 A CN 105503923A
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- pseudoallyl
- acid ester
- boric acid
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- -1 isopropenyl boric acid ester Chemical class 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000003407 synthetizing effect Effects 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 16
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 10
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims abstract description 8
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 8
- 150000007530 organic bases Chemical class 0.000 claims abstract description 8
- 229910052796 boron Inorganic materials 0.000 claims abstract description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 24
- 239000004327 boric acid Substances 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 16
- 230000002194 synthesizing effect Effects 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 229940043279 diisopropylamine Drugs 0.000 claims description 8
- 238000004821 distillation Methods 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 8
- ZUNGTEUNVMHDIX-UHFFFAOYSA-N (1-pyrimidin-2-ylpiperidin-4-yl)methanol Chemical compound C1CC(CO)CCN1C1=NC=CC=N1 ZUNGTEUNVMHDIX-UHFFFAOYSA-N 0.000 claims description 7
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 7
- 230000026030 halogenation Effects 0.000 claims description 7
- 238000005658 halogenation reaction Methods 0.000 claims description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 150000001336 alkenes Chemical class 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical group C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 claims description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 239000012044 organic layer Substances 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- WGLLSSPDPJPLOR-UHFFFAOYSA-N tetramethylethylene Natural products CC(C)=C(C)C WGLLSSPDPJPLOR-UHFFFAOYSA-N 0.000 claims description 4
- BNMUOEDPTZHSNX-UHFFFAOYSA-N B(Br)(Br)Br.C(C)(C)NC(C)C Chemical compound B(Br)(Br)Br.C(C)(C)NC(C)C BNMUOEDPTZHSNX-UHFFFAOYSA-N 0.000 claims description 3
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 3
- 150000007857 hydrazones Chemical class 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 150000002009 diols Chemical class 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 238000006116 polymerization reaction Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 description 6
- BMQDAIUNAGXSKR-UHFFFAOYSA-N (3-hydroxy-2,3-dimethylbutan-2-yl)oxyboronic acid Chemical compound CC(C)(O)C(C)(C)OB(O)O BMQDAIUNAGXSKR-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000007818 Grignard reagent Substances 0.000 description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 4
- 150000004795 grignard reagents Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- PNLQPWWBHXMFCA-UHFFFAOYSA-N 2-chloroprop-1-ene Chemical compound CC(Cl)=C PNLQPWWBHXMFCA-UHFFFAOYSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000004886 process control Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- PHMRPWPDDRGGGF-UHFFFAOYSA-N 2-bromoprop-1-ene Chemical group CC(Br)=C PHMRPWPDDRGGGF-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 229940121828 Phosphodiesterase 2 inhibitor Drugs 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical compound [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 150000001639 boron compounds Chemical class 0.000 description 1
- ITQYPUFOGQVEHR-UHFFFAOYSA-N boron;n-propan-2-ylpropan-2-amine Chemical compound [B].CC(C)NC(C)C ITQYPUFOGQVEHR-UHFFFAOYSA-N 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- NGPGYVQZGRJHFJ-UHFFFAOYSA-N chembl1604790 Chemical compound OC1=CC(O)=CC=C1N=NC1=CC=C([N+]([O-])=O)C=C1 NGPGYVQZGRJHFJ-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
The invention discloses a method for synthetizing isopropenyl boric acid ester. Acetone is used as a raw material and subjected to a reaction with hydrazine hydrate to generate hydrazone, then, isopropenyl halogen is generated at the existence of NXS and organic base and then subjected to a one-pot reaction with metallic lithium and bi(disopropylamine) boron halide, diol and a polymerization inhibitor are added for a backflow reaction to obtain isopropenyl boronic acid ester, and the yield is 65-69%,. The method is easy and convenient to implement, purification is convenient, the yield is high, no ultralow temperature reaction is needed, and the method is suitable for industrial enlarged production.
Description
Technical field
The present invention relates to a kind of method of synthesizing pseudoallyl boric acid ester, belong to pharmaceutical intermediate synthesis field.
Background technology
Pseudoallyl functional group is all very general in organic synthesis and pharmaceutical synthesis, conventional increase pseudoallyl carries out Suzuki coupling by pseudoallyl boron compound exactly to the method on aromatic ring, such as: pseudoallyl pinacol borate can be used for synthesizing pyrimidone amides phosphodiesterase 2 inhibitor (reference: WO2015096651A1) for the treatment of central nervous system disorder.
The synthesis of pseudoallyl boric acid ester mainly adopts at present: 2-bromopropylene is prepared into Grignard reagent, reacts with trimethyl borate, generates corresponding pseudoallyl boric acid, (reference: J.Am.Chem.Soc. is obtained after reacting with tetramethyl ethylene ketone more subsequently, 2006,128,16384).In this synthetic method, grignard reagent concentration has precipitation more than during 1M, needs first to obtain pseudoallyl boric acid simultaneously, and this boric acid poor stability, is easily polymerized, and degenerates in self dehydration still-process simultaneously.
Summary of the invention
In order to overcome above-mentioned defect, the invention discloses a kind of method of synthesizing pseudoallyl boric acid ester.Take acetone as raw material, react with hydrazine hydrate and generate hydrazone, then under NXS and organic bases exist, pseudoallyl halogen is generated, subsequently with metallic lithium and two (Diisopropylamine) halogenation boron one pot reaction, then glycol is added and stopper back flow reaction obtains pseudoallyl boric acid ester, yield 65-69%.
Synthesize a method for pseudoallyl boric acid ester, it is characterized in that comprising the following steps:
The first step: after acetone, hydrazine hydrate, anhydrous magnesium sulfate and methanol mixed, stirring at room temperature reacts complete filtration, solvent evaporated, add methylene dichloride and organic bases, temperature control-10 DEG C is to 0 DEG C, and dropping NXS is dissolved in the solution in methylene dichloride, after detection reaction is complete, after adding aqueous hydrochloric acid cancellation, separate organic layer, add tetramethylene sulfone, after atmospheric distillation, obtain pseudoallyl halogen, GC content more than 99%, yield 70-75%;
Second step: pseudoallyl halogen, to 0 DEG C, drops in two (Diisopropylamine) halogenation boron, metallic lithium and anhydrous ether solvent, is warmed up to 20 DEG C to 80 DEG C reactions subsequently by temperature control-10 DEG C; Reaction terminates, and adds glycol and stopper, back flow reaction; Reaction terminates, and add tetramethylene sulfone, underpressure distillation obtains pseudoallyl boric acid ester, GC content more than 99%, and long-time preservation needs additionally to add the stopper of product weight than 0.2-1%.
Further, in technique scheme, in the first step, organic bases is selected from pyridine, DMAP, triethylamine, diisopropyl ethyl amine or tetramethyl guanidine.
Further, in technique scheme, in the first step, NXS is selected from NCS, NBS or NIS, and the corresponding pseudoallyl halogen generated is respectively isopropyl alkene chlorine, isopropyl alkene bromine or isopropyl alkene iodine.
Further, in technique scheme, in the first step, acetone, hydrazine hydrate, anhydrous magnesium sulfate, organic bases and NXS equivalence ratio are 1:1-5:1-5:2-6:1-3.
Further, in technique scheme, in second step, anhydrous ether solvent is selected from tetrahydrofuran (THF) or 2-methyltetrahydrofuran.
Further, in technique scheme, in second step, two (Diisopropylamine) halogenation boron is selected from two (Diisopropylamine) boron chloride or two (Diisopropylamine) boron bromide.
Further, in technique scheme, in second step, glycol is selected from tetramethyl ethylene ketone or neopentyl glycol.
Further, in technique scheme, in second step, isopropyl alkene halogen, two (Diisopropylamine) halogenation boron, metallic lithium and glycol equivalence ratio are 1:1-1.3:2-2.5:1-1.5.
Further, in technique scheme, in second step, stopper is selected from thiodiphenylamine or 2,6 di tert butyl 4 methyl phenol.
The beneficial effect of the invention
The present invention has the following advantages:
1) synthetic route advantages of simple, raw materials used cheap and easy to get, product purity is high, is applicable to industrial amplification production.
2) just can be caught by halogen borane reagent immediately after isopropyl halide and metallic lithium form lithium reagent, reduce the impact of lithium reagent transformation period, improve yield; Avoid simultaneously and adopt azoviolet to prepare pseudoallyl grignard reagent concentration excessive, the problem that Grignard reagent is separated out.
3) two (Diisopropylamine) boron of the pseudoallyl generated due to steric hindrance large, stability is far away higher than pseudoallyl pinacol borate, by adding the large polar high-boiling solvent such as tetramethylene sulfone, facilitate the operation of amplification and decrease post-reaction treatment, reduce further the loss of intermediates.
4) intermediate product can be reacted from different glycol, and after adding stopper, after being replaced by Diisopropylamine, just can obtain sterling, operation is very easy.
Specific embodiments
Embodiment 1
The synthesis of pseudoallyl pinacol borate:
The first step: by acetone (58g, 1mol), 75% hydrazine hydrate (200g, 3mol), anhydrous magnesium sulfate (360g, 3mol) and 650mL methanol mixed after, stirring at room temperature reaction is complete, filters, then uses 30mL methanol wash solid, solvent evaporated, add 1200mL methylene dichloride and pyridine (312g, 4mol), temperature control-10 DEG C is to 0 DEG C, dropping NBS (356g, 2mol) is dissolved in the solution in 550mL methylene dichloride.After GC detection reaction is complete, adds 10% hydrochloric acid and adjust PH=3-4, separate organic layer, add 50mL tetramethylene sulfone, after atmospheric distillation separates methylene dichloride, receive 46-50 DEG C of cut, obtain 89.5g light yellow liquid pseudoallyl bromine, GC:99.2%, yield 74%;
Second step: by pseudoallyl bromine (89.5g, 0.74mol) be dissolved in 750mL tetrahydrofuran (THF), be added dropwise to two (Diisopropylamine) boron chloride (183g, 0.74mol), metallic lithium (10.4g, 1.5mol) with in 110mL tetrahydrofuran (THF), drip process control temperature of reaction at-10 DEG C to 0 DEG C.Dropwise and maintain this thermotonus 1 hour, rise to 25 DEG C subsequently and continue reaction 5 hours.After reaction terminates, add tetramethyl ethylene ketone (98g, 0.83mol), after 2,6 di tert butyl 4 methyl phenol (4.5g) and 120mL tetrahydrofuran (THF), temperature rising reflux reacts, reaction end adds 90mL tetramethylene sulfone, underpressure distillation obtains colourless transparent liquid pseudoallyl pinacol borate 82.1g, yield 66%, GC:99.7%, long-term preservation need add 2,6 di tert butyl 4 methyl phenol (0.45g).
Embodiment 2
The synthesis of pseudoallyl boric acid DOPCP:
The first step: by acetone (58g, 1mol), 75% hydrazine hydrate (200g, 3mol), anhydrous magnesium sulfate (360g, 3mol) and 650mL methanol mixed after, stirring at room temperature reaction is complete, filters, then uses 30mL methanol wash solid, solvent evaporated, add 1200mL methylene dichloride and triethylamine (506g, 5mol), temperature control-10 DEG C is to 0 DEG C, dropping NCS (334g, 2.5mol) is dissolved in the solution in 420mL methylene dichloride.After GC detection reaction is complete, add 10% hydrochloric acid and adjust PH=3-4, separate organic layer, add 20mL tetramethylene sulfone, atmospheric distillation receives 20-23 DEG C of cut, obtains 54.3g colourless liquid iso-propenyl chloride, GC:99.5%, yield 71%;
Second step: by iso-propenyl chloride (54.3g, 0.71mol) be dissolved in 450mL2-methyltetrahydrofuran, be added dropwise to two (Diisopropylamine) boron bromide (206g, 0.71mol), metallic lithium (10.4g, 1.5mol) with in 200mL2-methyltetrahydrofuran, drip process control temperature of reaction at-10 DEG C to 0 DEG C.Dropwise and maintain this thermotonus 2 hours, rise to 40 DEG C subsequently and continue reaction 3 hours.After reaction terminates, add neopentyl glycol (78g, 0.75mol), after thiodiphenylamine (8.5g) and 110mL2-methyltetrahydrofuran, temperature rising reflux reacts, reaction end adds 80mL tetramethylene sulfone, and underpressure distillation obtains colourless transparent liquid pseudoallyl pinacol borate 67.8g, yield 62%, GC:99.4%, long-term preservation need add thiodiphenylamine (0.67g).
Claims (9)
1. synthesize a method for pseudoallyl boric acid ester, it is characterized in that comprising the following steps:
The first step: after acetone, hydrazine hydrate, anhydrous magnesium sulfate and methanol mixed, stirring at room temperature reacts complete filtration, solvent evaporated, add methylene dichloride and organic bases, temperature control-10 DEG C is to 0 DEG C, and dropping NXS is dissolved in the solution in methylene dichloride, after detection reaction is complete, add aqueous hydrochloric acid cancellation, separate organic layer, add tetramethylene sulfone, after atmospheric distillation, obtain pseudoallyl halogen, GC content more than 99%, yield 70-75%;
Second step: pseudoallyl halogen, to 0 DEG C, drops in two (Diisopropylamine) halogenation boron, metallic lithium and anhydrous ether solvent, is warmed up to 20 DEG C to 80 DEG C reactions subsequently by temperature control-10 DEG C; Reaction terminates, and adds glycol and stopper, back flow reaction; Reaction terminates, and add tetramethylene sulfone, underpressure distillation obtains pseudoallyl boric acid ester, GC content more than 99%, and long-time preservation needs additionally to add the stopper of product weight than 0.2-1%.
2. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, it is characterized in that: in the first step, organic bases is selected from pyridine, DMAP, triethylamine, diisopropyl ethyl amine or tetramethyl guanidine.
3. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, it is characterized in that: in the first step, NXS is selected from NC, NBS or NIS, and the corresponding pseudoallyl halogen generated is respectively isopropyl alkene chlorine, isopropyl alkene bromine or isopropyl alkene iodine.
4. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, it is characterized in that: in the first step, acetone, hydrazine hydrate, anhydrous magnesium sulfate, organic bases and NXS equivalence ratio are 1:1-5:1-5:2-6:1-3.
5. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, it is characterized in that: in second step, anhydrous ether solvent is selected from tetrahydrofuran (THF) or 2-methyltetrahydrofuran.
6. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, is characterized in that: in second step, and two (Diisopropylamine) halogenation boron is selected from two (Diisopropylamine) boron chloride or two (Diisopropylamine) boron bromide.
7. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, it is characterized in that: in second step, glycol is selected from tetramethyl ethylene ketone or neopentyl glycol.
8. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, it is characterized in that: in second step, isopropyl alkene halogen, two (Diisopropylamine) halogenation boron, metallic lithium and glycol equivalence ratio are 1:1-1.3:2-2.5:1-1.5.
9. a kind of method of synthesizing pseudoallyl boric acid ester according to claim 1, it is characterized in that: in second step, stopper is selected from thiodiphenylamine or 2,6 di tert butyl 4 methyl phenol.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112321623A (en) * | 2020-10-23 | 2021-02-05 | 厦门大学 | Method for catalyzing hydroboration reaction of carbonyl compound |
| CN113735888A (en) * | 2021-09-06 | 2021-12-03 | 大连双硼医药化工有限公司 | Synthetic method of isopropenyl pinacol borate |
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2016
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Non-Patent Citations (5)
| Title |
|---|
| LIQIONG WANG ET AL.: "Metal catalyzed tandem DielseAlder/hydrolysis reactions of 2-boron-substituted 1,3-dienes", 《JOURNAL OF ORGANOMETALLIC CHEMISTRY》 * |
| MARIKA BLASKOVICOVA ET AL.: "Synthesis and Photochemistry of 1-Iodocyclohexene: Influence of Ultrasound on Ionic vs. Radical Behaviour", 《MOLECULES》 * |
| PAUL J. KROPP ET AL.: "Photochemistry of Alkyl Halides. 10. Vinyl Halides and Vinylidene Dihalides", 《J. AM. CHEM. SOC.》 * |
| PAUL KNOCHEL ET AL.: "Vinylmagnesium Bromide", 《E-EROS ENCYCLOPEDIA OF REAGENTS FOR ORGANIC SYNTHESIS》 * |
| YUICHI KOBAYASHI ET AL.: "Nickel-Catalyzed Coupling Reaction of Sterically Congested cis Bromides and Lithium Alkenylborates", 《TETRAHEDRON》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112321623A (en) * | 2020-10-23 | 2021-02-05 | 厦门大学 | Method for catalyzing hydroboration reaction of carbonyl compound |
| CN112321623B (en) * | 2020-10-23 | 2021-12-21 | 厦门大学 | Method for catalyzing hydroboration reaction of carbonyl compound |
| CN113735888A (en) * | 2021-09-06 | 2021-12-03 | 大连双硼医药化工有限公司 | Synthetic method of isopropenyl pinacol borate |
| CN113735888B (en) * | 2021-09-06 | 2024-02-27 | 大连双硼医药化工有限公司 | Synthetic method of isopropenylboronic acid pinacol ester |
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