CN104119211B - A kind of prepare ɑ-mono-bromo ketone and ɑ, ɑ-two method of brominated ketone compound by ketone compounds selective bromination - Google Patents
A kind of prepare ɑ-mono-bromo ketone and ɑ, ɑ-two method of brominated ketone compound by ketone compounds selective bromination Download PDFInfo
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- CN104119211B CN104119211B CN201410377248.XA CN201410377248A CN104119211B CN 104119211 B CN104119211 B CN 104119211B CN 201410377248 A CN201410377248 A CN 201410377248A CN 104119211 B CN104119211 B CN 104119211B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
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- 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
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- 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 kind of selective bromination ketone compounds and prepare ɑ-mono-bromo ketone and ɑ, the method of ɑ-two brominated ketone compound, using ketone compounds as reactant, bromic acid or mineral acid exist under bromate and metal bromide as brominated reagent, alcohol as solvent, can be corresponding ɑ-mono-bromo ketone by ketone compounds selective bromination; This reaction has that bromo selectivity is high, reaction conditions is gentle, speed of reaction and the high effect of yield, the brominated reagent selected low toxicity cheap and easy to get, and the utilization ratio of bromine is high, close to the requirement of Green Chemistry, therefore be easy to suitability for industrialized production, there is good application prospect.
Description
Technical field
The invention belongs to organic compound preparation technical field, be specifically related to a kind of ɑ-mono-bromo ketone and ɑ, ɑ-two method for selective production of brominated ketone compound.
Background technology
Various ɑ-mono-bromo ketone and ɑ, ɑ-two brominated ketone compound be the important intermediate of the fine chemicals such as medicine, agricultural chemicals, therefore their preparation method receives the extensive concern of investigator.ɑ-mono-bromo ketone and ɑ, ɑ-two preparation method of brominated ketone compound, normally directly carry 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.processRes.Dev., 2003,7,851; C.C.Silveira, C.R.Bernardi, A.L.Braga, T.S.Kaufman, TetrahedronLett., 2001,42 (51), 8947).But the simple substance bromine that this bromination process uses has, and toxicity is large, highly volatile, the unsafe feature of operation, pollute the environment in the industrial production and etching apparatus, and selectivity is poor, prepared product is often ɑ-mono-bromo ketone and ɑ, the mixture of ɑ-two brominated ketone compound, wherein the utilization ratio of bromine atoms is the highest is also only 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) be all better than simple substance bromine in selectivity and security, 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),, but potassium hydrogen persulfate has extremely strong corrodibility, is unfavorable for industrial production 3627); N-brominated reagent is as N-bromo-succinimide (M.V.Adihikar, S.D.Samant, UltrasonicsSonochem., 2002,9,107; I.Pravst, M.Zupan, S.Stavber, TetrahedronLett., 2006,47,4707), C5H6Br2N2O2 (Gao Guorui, Guan Xixia, Zou Xinzhuo, organic chemistry, 2007,27 (1), 109; And tribromo tricarbimide (L.S.deAlmeida CN1733677A), P.M.Esteves, M.C.S.deMattos, Synlett, 2006,1515) etc. bromo-reaction can be carried out under mild conditions, and alternative preparation ɑ-mono-bromo ketone and ɑ, ɑ-two brominated ketone compound, but such brominated reagent price is relatively high, and after sloughing bromine atoms, generate the by products such as succimide, dimethyl hydantion or isocyanide uraturia.Hydrogen peroxide and Hydrogen bromide mixture are the most green generally acknowledged brominated reagents, come into one's own in recent years, but their activity is not high, often need to use catalyzer as lithium chloride etc., and the reaction times reaches more than 24 hours, yield (A.Podgorsek, S.Stavber about medium-sized just can be reached, M.Zupan, J.Iskra, GreemChem., 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
A kind of selective bromination ketone compounds is the object of the present invention is to provide to prepare ɑ-mono-bromo ketone and ɑ respectively, the method of ɑ-two brominated ketone compound, this preparation method prepares ɑ-mono-brominated ketone compound and ɑ by the regulation and control highly selective of brominated reagent consumption, ɑ-two 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, and low toxicity, 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 selective bromination ketone compounds prepares ɑ-mono-bromo ketone and ɑ, the method of ɑ-two brominated ketone compound, wherein the method using ketone compounds as reactant, bromic acid or mineral acid exist under bromate and metal bromide as brominated reagent, alcohol as solvent, can be corresponding ɑ-mono-bromo ketone by ketone compounds selective bromination;
For being corresponding ɑ-mono-bromo ketone by ketone compound selective bromination, 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 selective bromination ketone compounds prepares ɑ-mono-bromo ketone and ɑ, the method of ɑ-two brominated ketone compound, wherein the method using ketone compounds as reactant, bromic acid or bromate and Hydrogen bromide as brominated reagent, alcohol as solvent, can be corresponding ɑ-mono-bromo ketone by ketone compounds selective bromination;
For being corresponding ɑ-mono-bromo ketone by ketone compound selective bromination, 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 selective bromination, ɑ-two bromo ketone.
For being corresponding ɑ by ketone compound selective bromination, ɑ-two 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).
For being corresponding ɑ, ɑ-two bromo ketone by ketone compound selective bromination, 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 containing-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, to react at room temperature ~ 90 DEG C reaction 1.5 ~ 8 hours;
C, revolve and steam except desolventizing, add ethyl acetate, organic layer washed with water, anhydrous sodium sulfate drying, filter, revolve and steam to obtain ɑ-mono-bromo ketone or ɑ, ɑ-two brominated ketone compound.
Described alcohol is methyl alcohol or ethanol, is preferably methyl alcohol.
When preparing ɑ-mono-bromo ketone or ɑ, ɑ-two brominated ketone compound, forming mixed solution by the raw material except letones, comprising 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 utilize bromate (or bromic acid) cheap and easy to get and metal bromide bromide (or Hydrogen bromide) in the presence of a mineral acid original position produce bromine and carry out brominated ketone compound, by the regulation and control of simple brominated reagent consumption, achieve selectivity and prepare ɑ-mono-bromo ketone and ɑ, ɑ-two 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 selected low toxicity cheap and easy to get, and the utilization ratio of bromine is high, close to 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
α-bromoacetophenone is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, 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%.
1HNMR(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
α-bromo-4-chloro-acetophenone is prepared 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, revolve except after recovery ethanol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated-4-chloro-acetophenone, productive rate 94%.
1HNMR(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
α-bromo-3-bromoacetophenone is prepared 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, revolve except after recovery ethanol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated-3-bromoacetophenone, productive rate 91%.
1HNMR(CDCl
3,300MHz)δ7.20–8.20(m,4H,ArH),4.38(s,2H,CH
2Br).
Embodiment 4
α-bromo-4-bromoacetophenone is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated-4-bromoacetophenone, productive rate 91%.
1HNMR(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
α-bromo-4-methoxyacetophenone is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the alpha-brominated-4-methoxyacetophenone of white solid, productive rate 97%, fusing point: 68-70 DEG C.HNMR(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
α-bromo-4-methyl acetophenone is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the alpha-brominated-4-methyl acetophenone of white solid, productive rate 98%, fusing point: 44-47 DEG C.
1HNMR(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
α-bromo-4-nitro-acetophenone is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain 4-nitro-acetophenone, productive rate 91%.
1HNMR(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
Chloro-α-the bromoacetophenone of 4-(4 '-chlorophenoxy)-2-is prepared 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 after recovery 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%.
1HNMR(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
2-bromo-acetoacetic ester is prepared 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, revolve except after recovery ethanol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain colourless liquid 2-bromo-acetoacetic ester productive rate 90%.
1HNMR(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
2-bromo diethyl malonate is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, 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%.
1HNMR(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
α is prepared, α-dibromobenzene ethyl ketone from methyl phenyl ketone selectivity two bromo:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α-dibromobenzene ethyl ketone, productive rate 98%.
1HNMR(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
α is prepared, the reaction of the bromo-4-chloro-acetophenone of α-two from 4-chloro-acetophenone selectivity bromo:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the bromo-4-chloro-acetophenone of α, α-two, productive rate 94%.
1HNMR(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
α is prepared, α, the reaction of 3 '-tribromo-benzene ethyl ketone from 3-bromoacetophenone selectivity bromo:
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, and add ethyl acetate 10mL and dissolve, 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%.
1HNMR(CDCl
3,500MHz)δ7.20–8.28(m,4H,ArH),6.75(s,1H,CHBr
2),
Embodiment 14
4-bromoacetophenone selectivity list bromo prepares α, α, 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, and add ethyl acetate 10mL and dissolve, 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%.
1HNMR(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 prepares α, the reaction of the bromo-4-fluoro acetophenone of α-two:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the bromo-4-fluoro acetophenone of α, α-two, productive rate 92%.
1HNMR(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 prepares α, the reaction of the bromo-4-methoxyacetophenone of α-two:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the bromo-4-methoxyacetophenone of α, α-two, productive rate 92%.
1HNMR(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 prepares α, the reaction of the bromo-4-methyl acetophenone of α-two:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the bromo-4-methyl acetophenone of α, α-two, productive rate 98%.
1HNMR(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 prepares α, the reaction of the bromo-4-trifluoromethyl acetophenone of α-two:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain the bromo-4-trifluoromethyl acetophenone of α, α-two, productive rate 93%.
1HNMR(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 prepares 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, revolve except after recovery ethanol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain 2-bromo-acetoacetic ester productive rate 90%.
1HNMR(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 prepares 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain 2-bromo diethyl malonate, productive rate 92%.
1HNMR(CDCl
3,500MHz)δ4.31(q,J＝7Hz,2H,OCH
2),1.32(t,J＝7Hz,3H,CH
3).
Comparative example 1
α-bromoacetophenone is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, 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%.
1HNMR(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
α-bromoacetophenone is prepared 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, revolve except after recovery methyl alcohol, add ethyl acetate 10mL and dissolve, 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%.
1HNMR(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
α is prepared, α-dibromobenzene ethyl ketone from methyl phenyl ketone selectivity two bromo:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α-dibromobenzene ethyl ketone, productive rate 91%.
1HNMR(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
α is prepared, α-dibromobenzene ethyl ketone from methyl phenyl ketone selectivity two bromo:
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, and add ethyl acetate 10mL and dissolve, water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain α, α-dibromobenzene ethyl ketone, productive rate 78%.
1HNMR(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).
As can be seen from embodiment 6,11 and 17, when the temperature of reaction in preparation process step B is 76 DEG C-79 DEG C, now ɑ-mono-bromo ketone or ɑ, the yield of ɑ-two brominated ketone compound can arrive 98%, described mixed solution and the mass ratio of ketone compounds are: during 1 ︰ 1 ~ 3 ︰ 1, now ɑ-mono-bromo ketone or ɑ, ɑ-two the yield of brominated ketone compound can reach more than 90%, and outside this scope, yield is not all more than 80%.
Claims (6)
1. a selective bromination ketone compounds prepares ɑ, the method of ɑ-two bromo ketone, it is characterized in that the method using ketone compounds as reactant, bromic acid or mineral acid exist under bromate and metal bromide as brominated reagent, water as solvent, can be corresponding ɑ, ɑ-two bromo ketone by ketone compounds selective bromination; Or the method using ketone compounds as reactant, bromic acid or bromate and Hydrogen bromide as brominated reagent, water as solvent, can be corresponding ɑ, ɑ-two bromo ketone by ketone compounds selective bromination; When preparing ɑ, ɑ-two brominated ketone compound, being made up of the raw material except letones and being called mixed solution, 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, react at 20 ~ 90 DEG C react 2 ~ 8 hours;
C, revolve and steam except desolventizing, add ethyl acetate, organic layer washed with water, anhydrous sodium sulfate drying, filter, revolve and steam to obtain ɑ, ɑ-two brominated ketone compound; Wherein, during preparation ɑ, ɑ-two 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 is than for 1:(0.6 ~ 1.0): (0.6 ~ 2.0); Wherein said ketone compounds is
in formula: R
1for-CH
3,-OC
2h
5,-OCH
3, phenyl, or containing-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.
2. method according to claim 1, is characterized in that described bromate is sodium bromate, the one in potassium bromate.
3. 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.
4. method according to claim 1, is characterized in that described mineral acid is the one in sulfuric acid, hydrochloric acid, Hydrogen bromide, phosphoric acid.
5. method according to claim 1, is characterized in that the mass ratio of described mixed solution and ketone compounds is: 1 ︰ 1 ~ 3 ︰ 1.
6. method according to claim 1, is characterized in that the temperature of reaction in step B is 76 DEG C-79 DEG C.
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| CN105461496B (en) * | 2015-12-14 | 2018-01-30 | 江苏强盛功能化学股份有限公司 | A kind of preparation method of the Dicarbonyl derivatives of 2 halo 1,3 |
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| CN111777506A (en) * | 2020-08-14 | 2020-10-16 | 上海嘉化科技有限公司 | Green chemical synthesis method of organic bromoacetic acid and ester |
| CN112391645B (en) * | 2020-11-24 | 2021-09-14 | 武汉大学 | Synthesis method for preparing alpha, alpha-dibromo-ketone by electrochemically oxidizing alkyne and bromide |
| CN114805044A (en) * | 2021-01-19 | 2022-07-29 | 兰州大学 | Novel method for synthesizing dibromo compound |
| CN113801005B (en) * | 2021-06-16 | 2023-06-13 | 浙江师范大学 | Preparation method of alpha-bromoacetophenone compound |
| CN114539019B (en) * | 2022-03-01 | 2023-11-28 | 苏州大学张家港工业技术研究院 | Method for continuously synthesizing halogenated compound by photoinduction based on halogen salt instead of halogen simple substance |
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