CN104119211A - Method for preparing alpha-monobrominated ketone and alpha, alpha-dibrominated ketone compounds by selectively brominating ketone compounds - Google Patents

Method for preparing alpha-monobrominated ketone and alpha, alpha-dibrominated ketone compounds by selectively brominating ketone compounds Download PDF

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CN104119211A
CN104119211A CN201410377248.XA CN201410377248A CN104119211A CN 104119211 A CN104119211 A CN 104119211A CN 201410377248 A CN201410377248 A CN 201410377248A CN 104119211 A CN104119211 A CN 104119211A
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ketone
bromo
bromide
bromate
ketone compounds
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CN104119211B (en
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韩冰冰
牛青龙
吴新虎
何在明
吴成凤
郑祖彪
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Huangshan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B39/00—Halogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms

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Abstract

The invention discloses a method for preparing alpha-monobrominated ketone and alpha, alpha-dibrominated ketone compounds by selectively brominating ketone compounds. The method comprises the steps of by taking ketone compounds as reactants, taking bromated and metal bromides in the presence of bromic acid or inorganic acid as brominating reagents and taking alcohol as a solvent, selectively brominating the ketone compounds into corresponding alpha-monobrominated ketone. The reaction has effects of high brominating selectivity, gentle reaction condition, high reaction velocity and high yield; the selected brominating reagents are cheap, easily available and low in toxicity; moreover, the method is high in bromine rate which is close to requirements of green chemistry, and therefore, the method is easy for industrial production and has good application prospect.

Description

One is prepared ɑ-mono-bromo ketone and ɑ, the method for ɑ-bis-brominated ketone compound by ketone compounds selectivity bromination
Technical field
The invention belongs to organic compound preparing technical field, be specifically related to a kind of ɑ-mono-bromo ketone and ɑ, the method for selective production of ɑ-bis-brominated ketone compound.
Background technology
Various ɑ-mono-bromo ketone and ɑ, ɑ-bis-brominated ketone compound is the important intermediate of the fine chemicals such as medicine, agricultural chemicals, therefore their preparation method has been subject to investigator's extensive concern.ɑ-mono-bromo ketone and ɑ, the preparation method of ɑ-bis-brominated ketone compound normally directly carries out bromo from bromine or bromine water by ketone compounds in different systems, as: (T.L.Stuk, B.K.Assink, R.C.Bates, D.T.Erdman, V.Fedij, S.M.Jennings, J.A.Lassing, R.J.Smith, T.L.Smith, Org.process Res.Dev., 2003,7,851; C.C.Silveira, C.R.Bernardi, A.L.Braga, T.S.Kaufman, Tetrahedron Lett., 2001,42 (51), 8947).But the simple substance bromine that this bromination process is used has, and toxicity is large, highly volatile, the unsafe feature of operation, in industrial production, pollute the environment and etching apparatus, and selectivity is poor, prepared product is often ɑ-mono-bromo ketone and ɑ, the mixture of ɑ-bis-brominated ketone compound, wherein the utilization ratio of bromine atoms is the highest is only also 50%; Cupric bromide (CuBr 2) also can be used as bromo agent (S.Caron, R.W.Dugger, S.G.Ruggeri, J.A.Ragan, D.H.B.Ripin, Chem.Rev.2006,106,2943) and in selectivity and security, be all better than simple substance bromine, but reactive behavior is relatively low; Potassium hydrogen persulfate and Sodium Bromide also can be used as brominated reagent (E.H.Kim, B.S.Koo, C.E.Song, K.J.Lee, Synth.Commun., 2001,31 (23), 3627), but potassium hydrogen persulfate has extremely strong corrodibility, is unfavorable for industrial production; N-brominated reagent is as N-bromo-succinimide (M.V.Adihikar, S.D.Samant, Ultrasonics Sonochem., 2002,9,107; I.Pravst, M.Zupan, S.Stavber, Tetrahedron Lett., 2006,47,4707), C5H6Br2N2O2 (Gao Guorui, Guan Xixia, Zou Xinzhuo, organic chemistry, 2007,27 (1), 109; CN 1733677A) and tribromo tricarbimide (L.S.de Almeida, P.M.Esteves, M.C.S.de Mattos, Synlett, 2006,1515) etc. can under gentle condition, carry out bromo-reaction, and alternative preparation ɑ-mono-bromo ketone and ɑ, ɑ-bis-brominated ketone compound, but such brominated reagent price is relatively high, and generate the by products such as succimide, dimethyl hydantion or isocyanide uraturia after sloughing bromine atoms.Hydrogen peroxide and Hydrogen bromide mixture are the most green brominated reagents of generally acknowledging, come into one's own in recent years, but their activity are not high, often need to use catalyzer as lithium chloride etc., and the reaction times reaches more than 24 hours, just can reach yield (A.Podgorsek, S.Stavber about medium-sized, M.Zupan, J.Iskra, Greem Chem., 2007,9,1212; A.Moghimi, S.Ranmani, R.Zare, M.Sadeghzadeh, S.Faraji, Iran.J.Org.Chem., 2011,3 (3), 707).
Summary of the invention
The object of the present invention is to provide a kind of selectivity bromination ketone compounds to prepare respectively ɑ-mono-bromo ketone and ɑ, the method of ɑ-bis-brominated ketone compound, this preparation method can prepare ɑ-mono-brominated ketone compound and ɑ by the regulation and control highly selective of brominated reagent consumption, ɑ-bis-brominated ketone compound, the reaction times is short, operational safety, react rear substantially no acidic waste liquid, raw material is cheap and easy to get simultaneously, low toxicity, and production cost is low.Its selectivity syntheti c route is as follows:
For solving the problems of the technologies described above, the technical solution used in the present invention is:
A kind of selectivity bromination ketone compounds is prepared ɑ-mono-bromo ketone and ɑ, the method of ɑ-bis-brominated ketone compound, wherein the method using ketone compounds as reactant, bromate under existing of bromic acid or mineral acid and metal bromide be as brominated reagent, alcohol as solvent, can be corresponding ɑ-mono-bromo ketone by ketone compounds selectivity bromination;
Wish is corresponding ɑ-mono-bromo ketone by ketone compound selectivity bromination, and the amount of substance of described ketone compounds, bromic acid or bromate, metal bromide, mineral acid is than being 1:(0.3～0.5): (0.3～1.0): (0.8～2.0).
A kind of selectivity bromination ketone compounds is prepared ɑ-mono-bromo ketone and ɑ, the method of ɑ-bis-brominated ketone compound, wherein the method using ketone compounds as reactant, bromic acid or bromate and Hydrogen bromide be as brominated reagent, alcohol as solvent, can be corresponding ɑ-mono-bromo ketone by ketone compounds selectivity bromination;
Wish is corresponding ɑ-mono-bromo ketone by ketone compound selectivity bromination, and described ketone compounds, bromic acid or bromate, hydrobromic amount of substance are than being 1:(0.3～0.5): (0.3～1.0).
And replace alcohol as solvent using water in above-mentioned two schemes, and can be corresponding ɑ by ketone compounds selectivity bromination, ɑ-bis-bromo ketone.
Wish is corresponding ɑ by ketone compound selectivity bromination, ɑ-bis-bromo ketone, the amount of substance of described ketone compounds, bromic acid or bromate, metal bromide, mineral acid is than being 1:(0.6～1.0): (0.6～2.0): (1.0～4.0).
Wish is corresponding ɑ by ketone compound selectivity bromination, ɑ-bis-bromo ketone, described ketone compounds, bromic acid or bromate, hydrobromic amount of substance are than being 1:(0.6～1.0): (0.6～2.0).
Described ketone compounds is in formula:
R 1for-CH 3,-OC 2h 5,-OCH 3, phenyl, or contain-CH 3,-OCH 3,-OPh ,-Cl ,-Br ,-I ,-F ,-NO 2the substituted-phenyl of 1～3 in substituting group; R 2for-H ,-COOCH 3,-COOC 2h 5in one.
Described bromate is sodium bromate, the one in potassium bromate.
Described metal bromide is Sodium Bromide, Potassium Bromide, magnesium bromide, iron bromide, lithiumbromide, brometo de amonio, the one in Tetrabutyl amonium bromide.
Described mineral acid is the one in sulfuric acid, hydrochloric acid, Hydrogen bromide, phosphoric acid.
Concrete reactions steps is:
A, take ketone compounds, bromic acid or bromate, Hydrogen bromide or metal bromide, mineral acid by proportional quantity, add in reaction vessel, and reaction solvent alcohol is added in reaction vessel;
B, reaction are reacted 1.5～8 hours at room temperature～90 DEG C;
C, revolve and steam except desolventizing, add ethyl acetate, organic layer washes with water, and anhydrous sodium sulfate drying filters, and revolves and steams to obtain ɑ-mono-bromo ketone or ɑ, ɑ-bis-brominated ketone compound.
Described alcohol is methyl alcohol or ethanol, is preferably methyl alcohol.
At preparation ɑ-mono-bromo ketone or ɑ, when ɑ-bis-brominated ketone compound, form mixed solution by the raw material except letones, comprise bromic acid or bromate, Hydrogen bromide or metal bromide or mineral acid
The mass ratio of described mixed solution and ketone compounds is: 2 ︰ 1～3 ︰ 1.
The present invention utilizes bromate cheap and easy to get (or bromic acid) and metal bromide bromide (or Hydrogen bromide) original position generation bromine under mineral acid exists to carry out brominated ketone compound, by the regulation and control of simple brominated reagent consumption, realize selectivity and prepared ɑ-mono-bromo ketone and ɑ, ɑ-bis-brominated ketone compound.This reaction has that bromo selectivity is high, reaction conditions is gentle, speed of reaction and the high effect of yield, the brominated reagent low toxicity cheap and easy to get of selecting, and the utilization ratio of bromine is high, approaches the requirement of Green Chemistry, therefore be easy to suitability for industrialized production, there is good application prospect.
Embodiment
Be below specific embodiments more of the present invention, but the present invention is not only confined to following examples.
Embodiment 1
Prepare α-bromoacetophenone from methyl phenyl ketone selectivity list bromo:
Methyl phenyl ketone 10mmol, potassium bromate 3.3mmol, Hydrogen bromide 10mmol, methyl alcohol 10mL, 60 DEG C, stopped reaction after stirring 2.5h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the alpha-brominated methyl phenyl ketone of white solid, productive rate 95%. 1H?NMR(CDCl 3,300MHz)δ8.00-8.03(m,2H,ArH),7.68-7.70(m,1H,ArH),4.44(s,2H,CH 2Br)。
Embodiment 2
Prepare α-bromo-4-chloro-acetophenone from 4-chloro-acetophenone selectivity list bromo:
4-chloro-acetophenone 10mmol, sodium bromate 3mmol, Sodium Bromide 6mmol, sulfuric acid 11mmol, ethanol 10mL, 70 DEG C, stopped reaction after stirring 1.5h, revolves except reclaiming after ethanol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam alpha-brominatedly-4-chloro-acetophenone, productive rate 94%. 1H?NMR(CDCl 3,300MHz)δ7.94(d,J＝8.4Hz,2H,ArH),7.48(d,J＝8.4Hz,2H,ArH),4.41(s,2H,CH 2Br).
Embodiment 3
Prepare α-bromo-3-bromoacetophenone from 3-bromoacetophenone selectivity list bromo:
3-bromoacetophenone 10mmol, sodium bromate 3.5mmol, Sodium Bromide 7mmol, phosphoric acid 8mmol, ethanol 10mL, 70 DEG C, stopped reaction after stirring 2h, revolves except reclaiming after ethanol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam alpha-brominatedly-3-bromoacetophenone, productive rate 91%. 1H?NMR(CDCl 3,300MHz)δ7.20–8.20(m,4H,ArH),4.38(s,2H,CH 2Br).
Embodiment 4
Prepare α-bromo-4-bromoacetophenone from 4-bromoacetophenone selectivity list bromo:
4-bromoacetophenone 10mmol, sodium bromate 4mmol, lithiumbromide 8mmol, sulfuric acid 15mmol, methyl alcohol 10mL, 70 DEG C, stopped reaction after stirring 2h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam alpha-brominatedly-4-bromoacetophenone, productive rate 91%. 1H?NMR(CDCl 3,300MHz)δ7.85(d,J＝8.5Hz,2H,ArH),7.65(d,J＝8.78Hz,2H,ArH),4.40(s,2H,CH 2Br).
Embodiment 5
Prepare α-bromo-4-methoxyacetophenone from 4-methoxyacetophenone selectivity list bromo:
4-methoxyacetophenone 10mmol, potassium bromate 4mmol, magnesium bromide 4mmol, concentrated hydrochloric acid 20mmol, methyl alcohol 10mL, 40 DEG C, stopped reaction after stirring 1.5h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve steam white solid alpha-brominated-4-methoxyacetophenone, productive rate 97%, fusing point: 68-70 DEG C.H?NMR(CDCl 3,300MHz)δ7.97(d,J＝8.78Hz,2H,ArH),6.95(d,J＝9.05Hz,2H,ArH),4.45(s,2H,CH 2Br),3.91(s,3H,OCH 3).
Embodiment 6
Prepare α-bromo-4-methyl acetophenone from 4-methyl acetophenone selectivity list bromo:
4-methyl acetophenone 10mmol, bromic acid 4mmol, iron bromide 3mmol, Hydrogen bromide 18mmol, methyl alcohol 10mL, 76 DEG C, stopped reaction after stirring 2h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve steam white solid alpha-brominated-4-methyl acetophenone, productive rate 98%, fusing point: 44-47 DEG C. 1H?NMR(CDCl 3,300MHz)δ7.88(d,J＝8.1Hz,2H,ArH),7.26(d,J＝8.1Hz,2H,ArH),4.40(s,2H,CH 2Br),2.38(s,3H,CH 3).
Embodiment 7
Prepare α-bromo-4-nitro-acetophenone from 4-nitro-acetophenone selectivity list bromo:
4-nitro-acetophenone 10mmol, potassium bromate 4.5mmol, Tetrabutyl amonium bromide 9mmol, sulfuric acid 15mmol, methyl alcohol 10mL, 90 DEG C, stopped reaction after stirring 3h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain 4-nitro-acetophenone, productive rate 91%. 1H?NMR(CDCl 3,300MHz)δ8.35(d,J＝8.0Hz,2H,ArH),8.18(d,J＝8.0Hz,2H,ArH),4.52(s,2H,CH 2Br).
Embodiment 8
Prepare the chloro-α-bromoacetophenone of 4-(4 '-chlorophenoxy)-2-from 4-(4 '-chlorophenoxy)-2-chloro-acetophenone
4-(4 '-chlorophenoxy)-2-chloro-acetophenone 10mmol, potassium bromate 4.5mmol, Potassium Bromide 9mmol, sulfuric acid 10mmol, methyl alcohol 10mL, 60 DEG C, stopped reaction after stirring 3h, revolves except reclaiming after methyl alcohol, add ethyl acetate 10mL to dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the chloro-α-bromoacetophenone of 4-(4 '-chlorophenoxy)-2-, productive rate 97%. 1H?NMR(CDCl 3,300MHz)δ7.66(d,J＝8.7Hz,1H,ArH),7.39(d,J＝8.8Hz,2H,ArH),7.02(d,J＝8.8Hz,2H,ArH),6.99(d,J＝2.4Hz,1H,ArH),6.92(dd,J＝8.7,2.4Hz,1H,ArH),4.7(s,2H,CH 2Br).
Embodiment 9
Prepare 2-bromo-acetoacetic ester from methyl aceto acetate selectivity list bromo:
Methyl aceto acetate 10mmol, potassium bromate 3mmol, Potassium Bromide 6mmol, sulfuric acid 10mmol, ethanol 10mL, room temperature, stopped reaction after stirring 1.5h, revolves except reclaiming after ethanol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain colourless liquid 2-bromo-acetoacetic ester productive rate 90%. 1H?NMR(CDCl 3,300MHz)δ4.76(s,1H,CHBr),4.29(q,2H,OCH 2),2.44(s,3H,CH 3),1.2(t,3H,CH 3)
Embodiment 10
Prepare 2-bromo diethyl malonate from diethyl malonate selectivity list bromo:
Diethyl malonate 10mmol, potassium bromate 4.5mmol, brometo de amonio 9mmol, sulfuric acid 15mmol, methyl alcohol 10mL, 40 DEG C, stopped reaction after stirring 3h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain weak yellow liquid 2-bromo diethyl malonate, productive rate 90%. 1H?NMR(CDCl 3,300MHz)δ4.85(s,1H,CHBr),4.30(q,J＝7Hz,4H,OCH 2),1.31(t,J＝7Hz,6H,CH 3).
Embodiment 11
Prepare α from methyl phenyl ketone selectivity two bromos, α-dibromobenzene ethyl ketone:
Methyl phenyl ketone 10mmol, potassium bromate 6.0mmol, Hydrogen bromide 20mmol, water 10mL, 78 DEG C, stopped reaction after stirring 4h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α-dibromobenzene ethyl ketone, productive rate 98%. 1H?NMR(CDCl 3,300MHz)δ8.08-8.05(m,2H,ArH),7.66-7.60(m,1H,ArH),7.52-7.47(m,2H,ArH),6.76(s,1H,CHBr 2).
Embodiment 12
Prepare α from 4-chloro-acetophenone selectivity bromo, the reaction of the bromo-4-chloro-acetophenone of α-bis-:
4-chloro-acetophenone 10mmol, sodium bromate 6mmol, Sodium Bromide 12mmol, sulfuric acid 20mmol, water 10mL, 80 DEG C, stopped reaction after stirring 5h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, the bromo-4-chloro-acetophenone of α-bis-, productive rate 94%. 1H?NMR(CDCl 3,300MHz)δ8.06(d,J＝8.4Hz,2H,ArH),7.43(d,J＝8.4Hz,2H,ArH),6.64(s,1H,CHBr 2).
Embodiment 13
Prepare α from 3-bromoacetophenone selectivity bromo, α, the reaction of 3 '-tribromo-benzene ethyl ketone:
3-bromoacetophenone 10mmol, bromic acid 7mmol, Sodium Bromide 14mmol, phosphatase 11 0mmol, water 10mL, 80 DEG C, stopped reaction after stirring 6h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α, 3 '-tribromo-benzene ethyl ketone, productive rate 92%. 1H?NMR(CDCl 3,500MHz)δ7.20–8.28(m,4H,ArH),6.75(s,1H,CHBr 2),
Embodiment 14
4-bromoacetophenone selectivity list bromo is prepared α, α, and the reaction of 4 '-tribromo-benzene ethyl ketone:
4-bromoacetophenone 10mmol, sodium bromate 8mmol, lithiumbromide 16mmol, sulfuric acid 20mmol, water 10mL, 80 DEG C, stopped reaction after stirring 6h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α, 4 '-tribromo-benzene ethyl ketone, productive rate 93%. 1H?NMR(300MHz,CDCl 3)δ7.98(d,J＝8.50Hz,2H),7.65(d,J＝8.78Hz,2H,),6.6(s,1H,CHBr 2).
Embodiment 15
4-fluoro acetophenone selectivity list bromo is prepared α, the reaction of the bromo-4-fluoro acetophenone of α-bis-:
4-fluoro acetophenone 10mmol, bromic acid 8mmol, lithiumbromide 16mmol, phosphoric acid 35mmol, water 10mL, 80 DEG C, stopped reaction after stirring 6h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, the bromo-4-fluoro acetophenone of α-bis-, productive rate 92%. 1H?NMR(300MHz,CDCl 3)δ8.10–8.40(m,2H,ArH),7.05–7.50(m,2H,ArH),6.70(s,1H,CHBr 2),
Embodiment 16
4-methoxyacetophenone selectivity list bromo is prepared α, the reaction of the bromo-4-methoxyacetophenone of α-bis-:
4-methoxyacetophenone 10mmol, potassium bromate 8mmol, magnesium bromide 8mmol, concentrated hydrochloric acid 40mmol, water 10mL, 60 DEG C, stopped reaction after stirring 1.5h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, the bromo-4-methoxyacetophenone of α-bis-, productive rate 92%. 1H?NMR(300MHz,CDCl 3)δ8.08(d,J＝9.05Hz,2H,ArH),6.97(d,J＝8.78Hz,2H,ArH),6.66(s,1H,CHBr 2),3.90(s,3H,OCH 3).
Embodiment 17
4-methyl acetophenone selectivity list bromo is prepared α, the reaction of the bromo-4-methyl acetophenone of α-bis-:
4-methyl acetophenone 10mmol, potassium bromate 8mmol, iron bromide 6mmol, Hydrogen bromide 18mmol, water 10mL, 79 DEG C, stopped reaction after stirring 2h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, the bromo-4-methyl acetophenone of α-bis-, productive rate 98%. 1H?NMR(300MHz,CDCl 3)δ7.98(d,J＝8.1Hz,2H,ArH),7.30(d,J＝8.1Hz,2H,ArH),6.69(s,1H,CHBr 2),2.44(s,3H,CH 3).
Embodiment 18
4-trifluoromethyl acetophenone selectivity list bromo is prepared α, the reaction of the bromo-4-trifluoromethyl acetophenone of α-bis-:
4-trifluoromethyl acetophenone 10mmol, bromic acid 6mmol, iron bromide 6mmol, Hydrogen bromide 35mmol, water 10mL, 90 DEG C, stopped reaction after stirring 2h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, the bromo-4-trifluoromethyl acetophenone of α-bis-, productive rate 93%. 1H?NMR(300MHz,CDCl 3)δ8.23(d,J＝8.3Hz,2H,ArH),7.70(d,J＝8.3Hz,2H,ArH),6.69(s,1H,CHBr 2).
Embodiment 19
Methyl aceto acetate selectivity list bromo is prepared the reaction of 2-bromo-acetoacetic ester:
Methyl aceto acetate 10mmol, potassium bromate 6mmol, Potassium Bromide 12mmol, sulfuric acid 20mmol, ethanol 10mL, 40 DEG C, stopped reaction after stirring 1.5h, revolves except reclaiming after ethanol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain 2-bromo-acetoacetic ester productive rate 90%. 1H?NMR(CDCl 3,500MHz)δ1.30(t,J＝7Hz,3H,CH 3),2.45(s,3H,CH 3CO),4.28(q,J＝7Hz,2H,CO 2CH 2)
Embodiment 20
Diethyl malonate selectivity list bromo is prepared the reaction of 2-bromo diethyl malonate:
Diethyl malonate 10mmol, potassium bromate 9mmol, brometo de amonio 18mmol, sulfuric acid 20mmol, methyl alcohol 10mL, 90 DEG C, stopped reaction after stirring 4h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain 2-bromo diethyl malonate, productive rate 92%. 1H?NMR(CDCl 3,500MHz)δ4.31(q,J＝7Hz,2H,OCH 2),1.32(t,J＝7Hz,3H,CH 3).
Comparative example 1
Prepare α-bromoacetophenone from methyl phenyl ketone selectivity list bromo:
Methyl phenyl ketone 10mmol, potassium bromate 3.3mmol, Hydrogen bromide 10mmol, methyl alcohol 10mL, 15 DEG C, stopped reaction after stirring 2.5h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the alpha-brominated methyl phenyl ketone of white solid, productive rate 75%. 1H?NMR(CDCl 3,300MHz)δ8.00-8.03(m,2H,ArH),7.68-7.70(m,1H,ArH),4.44(s,2H,CH 2Br)。
Comparative example 2
Prepare α-bromoacetophenone from methyl phenyl ketone selectivity list bromo:
Methyl phenyl ketone 10mmol, potassium bromate 3.3mmol, Hydrogen bromide 10mmol, methyl alcohol 10mL, 100 DEG C, stopped reaction after stirring 2.5h, revolves except reclaiming after methyl alcohol, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the alpha-brominated methyl phenyl ketone of white solid, productive rate 77%. 1H?NMR(CDCl 3,300MHz)δ8.00-8.03(m,2H,ArH),7.68-7.70(m,1H,ArH),4.44(s,2H,CH 2Br)。
Comparative example 3
Prepare α from methyl phenyl ketone selectivity two bromos, α-dibromobenzene ethyl ketone:
Methyl phenyl ketone 10mmol, potassium bromate 6.0mmol, Hydrogen bromide 20mmol, water 10mL, 75 DEG C, stopped reaction after stirring 4h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α-dibromobenzene ethyl ketone, productive rate 91%. 1H?NMR(CDCl 3,300MHz)δ8.08-8.05(m,2H,ArH),7.66-7.60(m,1H,ArH),7.52-7.47(m,2H,ArH),6.76(s,1H,CHBr 2).
Comparative example 4
Prepare α from methyl phenyl ketone selectivity two bromos, α-dibromobenzene ethyl ketone:
Methyl phenyl ketone 10mmol, potassium bromate 6.0mmol, Hydrogen bromide 20mmol, water 10mL, 100 DEG C, stopped reaction after stirring 4h, revolves except after recycle-water, adds ethyl acetate 10mL to dissolve, and water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α-dibromobenzene ethyl ketone, productive rate 78%. 1H?NMR(CDCl 3,300MHz)δ8.08-8.05(m,2H,ArH),7.66-7.60(m,1H,ArH),7.52-7.47(m,2H,ArH),6.76(s,1H,CHBr 2).
Can be found out by embodiment 6,11 and 17, in the time that the temperature of reaction in preparation process B step is 76 DEG C-79 DEG C, now ɑ-mono-bromo ketone or ɑ, the yield of ɑ-bis-brominated ketone compound can arrive 98%, described mixed solution and the mass ratio of ketone compounds are: when 1 ︰ 1～3 ︰ 1, and now ɑ-mono-bromo ketone or ɑ, the yield of ɑ-bis-brominated ketone compound can reach more than 90%, and outside this scope, yield does not all exceed 80%.

Claims (10)

1. a selectivity bromination ketone compounds is prepared ɑ-mono-bromo ketone or ɑ, the method of ɑ-bis-bromo ketone, it is characterized in that the method using ketone compounds as reactant, bromate under existing of bromic acid or mineral acid and metal bromide be as brominated reagent, alcohol as solvent, can be corresponding ɑ-mono-bromo ketone by ketone compounds selectivity bromination; Or the method using ketone compounds as reactant, bromic acid or bromate and Hydrogen bromide be as brominated reagent, alcohol as solvent, can be corresponding ɑ-mono-bromo ketone by ketone compounds selectivity bromination; In above-mentioned two schemes, replacing alcohol as solvent using water, can be corresponding ɑ by ketone compounds selectivity bromination, ɑ-bis-bromo ketone; At preparation ɑ-mono-bromo ketone or ɑ, when ɑ-bis-brominated ketone compound, form and be called mixed solution by the raw material except letones, comprise bromic acid or bromate, Hydrogen bromide or metal bromide or mineral acid;
Concrete steps comprise:
A, take above-mentioned reaction raw materials by proportional quantity, add in reaction vessel, and reaction solvent is added in reaction vessel;
B, reaction are reacted 2～8 hours at 20～90 DEG C;
C, revolve and steam except desolventizing, add ethyl acetate, organic layer washes with water, and anhydrous sodium sulfate drying filters, and revolves and steams to obtain ɑ-mono-bromo ketone or ɑ, ɑ-bis-brominated ketone compound.
2. method according to claim 1, is characterized in that described ketone compounds is in formula: R 1for-CH 3,-OC 2h 5,-OCH 3, phenyl, or contain-CH 3,-OCH 3,-OPh ,-Cl ,-Br ,-I ,-F ,-CF 3,-NO 2the substituted-phenyl of 1～3 in substituting group; R 2for-H ,-COOCH 3,-COOC 2h 5in one.
3. method according to claim 1, is characterized in that described bromate is sodium bromate, the one in potassium bromate.
4. method according to claim 1, is characterized in that described metal bromide is Sodium Bromide, Potassium Bromide, magnesium bromide, iron bromide, lithiumbromide, brometo de amonio, the one in Tetrabutyl amonium bromide.
5. method according to claim 1, is characterized in that described mineral acid is the one in sulfuric acid, hydrochloric acid, Hydrogen bromide, phosphoric acid.
6. method according to claim 1, it is characterized in that, when preparation ɑ-mono-bromo ketone, described ketone compounds, bromic acid or bromate are 1:(0.3～0.5 with the amount of substance ratio of metal bromide, mineral acid): (0.3～1.0): (0.8～2.0); Or described ketone compounds, bromic acid or bromate, hydrobromic amount of substance are than being 1:(0.3～0.5): (0.3～1.0).
7. method according to claim 1, it is characterized in that, preparation ɑ, when ɑ-bis-bromo ketone, the amount of substance of described ketone compounds, bromic acid or bromate, metal bromide, mineral acid is than being 1:(0.6～1.0): (0.6～2.0): (1.0～4.0); Or described ketone compounds, bromic acid or bromate, hydrobromic amount of substance are than being 1:(0.6～1.0): (0.6～2.0).
8. method according to claim 1, is characterized in that described alcohol is methyl alcohol or ethanol, particular methanol.
9. method according to claim 1, is characterized in that described mixed solution and the mass ratio of ketone compounds are: 1 ︰ 1～3 ︰ 1.
10. method according to claim 1, is characterized in that the temperature of reaction in B step is 76 DEG C-79 DEG C.
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CN113801005A (en) * 2021-06-16 2021-12-17 浙江师范大学 Preparation method of alpha-bromoacetophenone compound
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