CN105884603A - Method for preparing substituted ketone compound through oxidization, dehydration and alkylation of secondary alcohol - Google Patents

Method for preparing substituted ketone compound through oxidization, dehydration and alkylation of secondary alcohol Download PDF

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CN105884603A
CN105884603A CN201610381667.XA CN201610381667A CN105884603A CN 105884603 A CN105884603 A CN 105884603A CN 201610381667 A CN201610381667 A CN 201610381667A CN 105884603 A CN105884603 A CN 105884603A
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secondary alcohol
reaction
alkylation
compound
ketone
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徐清
李洋
李双艳
李欢
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Wenzhou University
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Wenzhou University
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    • 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
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
    • C07C45/37—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups
    • C07C45/39—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups being a secondary hydroxyl group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
    • C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention discloses a method for preparing a substituted ketone compound through oxidization, dehydration and alkylation of secondary alcohol, and by means of the green synthetic method, substituted ketones are prepared from primary alcohol and the secondary alcohol through a dehydration C-alkylation-oxidization cascade reaction with the existence of alkali but without a transitional metal catalyst. According to the method, the alcohols which are low in price, easy to obtain, wide in source, stable and low in toxicity are used as alkylation reagent, common base metal inorganic base is used as an additive, methylbenzene is used as solvent, air is economical and safe oxidant, and the corresponding substituted ketone compound with secondary alcohol beta alkylated is directly synthesized through the dehydration C-alkylation-oxidization cascade reaction. The reaction method and condition are simple, no transitional metal catalyst is need, no inert gas protection is needed, the method is easy to operate, the by-product is water, compared with a precious metal catalyst, the inorganic base which is used is low in price and easy to obtain and can be removed conveniently through washing, and no heavy metal residue exists in the final product. Therefore, the method is wide in application scope and has certain research and industrial application prospect.

Description

The method that the oxidation dewatering alkylation preparation of a kind of secondary alcohol replaces ketone compounds
Technical field
The invention belongs to the field of chemical synthesis, be specifically related to one by primary and secondary alcohol by dehydration The method that C-alkylation-oxidation cascade reaction preparation replaces ketone compounds, it is a kind of nontoxic Environment-friendly preparation method thereof.
Background technology
The structure of C-C key is in vital effect, wherein a carbonyl in organic synthesis The conjunction that compound alpha-position official energy dough guides at heterocyclic compound, pharmaceutical intermediate, natural product Become to have important application, associated research to cause the weight of chemistry and biochemical research circle Depending on.In traditional synthetic method, usual alpha-position official can the carbonyl compound of dough be by with carbonyl Based compound and halohydrocarbons reaction, but these methods need have reactivity and the halogen of severe toxicity For hydrocarbon and substantial amounts of alkali, reaction the most inevitably generates substantial amounts of useless salt.Compare For, alcohol is a class organic compound more green than halogenated hydrocarbons, has evolved into green The alkylating reagent of color, and much halogenated hydrocarbons is also obtained through halogenation synthesis by alcohol.Closely Nian Lai, chemists developed under a series of transition metal-catalyzed oxygen free condition by means of hydrogen or hydrogen Automatically transfer method realizes dehydration N-or C-alkylated reaction, the most also includes methyl ketone Compound and the α-C-alkylated reaction of alcohol.But these methods still have obvious shortcoming, such as, need to make With expensive and have virose noble metal catalyst Ru, Ir, Pd etc. and the complicated part sent out, Using substantial amounts of dehydrating agent and alkali, reaction need to be carried out under anaerobic, otherwise metal catalytic Agent easily inactivates, and simultaneous reactions product there may be the residual of heavy metal and causes quality to reduce.
Therefore, exploitation realizes the reaction system of alcohol without new method one step that transition-metal catalyst participates in Being on the waiting list for ketone compounds is significantly to study.It is contemplated that exploitation is a kind of without transition Under metal participates in, alkali be reaction promoter, using green alcohol as the primary alconol of alkylating reagent with Secondary alcohol is synthesized the new method replacing ketone compounds.
Summary of the invention
The invention aims to the shortcoming and defect overcoming prior art to exist, and provide one Planting the method that secondary alcohol oxidation dewatering alkylation preparation replaces ketone compounds, the method uses originates Extensively, alcohols cheap and easy to get, that stablize low toxicity be alkylating reagent, without transition metal-catalyzed In the presence of agent, under the promotion of alkali, solvent made by toluene, air is oxidant, it is achieved primary alconol and The water C-alkylation of secondary alcohol-oxidation cascade reaction preparation replaces the green method of ketone compounds, By-product is water, efficient pollution-free.
For achieving the above object, the technical scheme is that
Primary alconol and secondary alcohol alkali metal inorganic base and at air conditions under, with the oxygen in air be Oxidant directly carries out dewatering alkylation-oxidation reaction and obtains replacing ketone compounds, reaction temperature Degree is 100～130 DEG C, and the response time is 12-60 hour, and by-product is water, and reaction equation is:
Arranging further is in secondary alcohol, R1It is that H or various group is substituted in 2-, 3-, 4-position Phenyl or other aryl, polysubstituted phenyl or other aryl；Or R1It is various carbochains The secondary alcohol of length and the fatty alkyl of substitution in side chain or naphthane alcohol class formation (is tied as follows Structure).
Arranging further is in primary alconol, R2It is that phenyl, various group are substituted in 2-, 3-, 4- The phenyl of position or other aryl, polysubstituted phenyl or other aryl or substituted heteroaryl Base.
Arrange further be alkali metal inorganic base be NaOH, KOH or CsOH.
Arrange further be the consumption of alkali metal inorganic base be 50～200mol%.
Arranging further is to react in organic solvent or carry out under condition of no solvent.
Arrange further is that reaction is carried out using toluene as solvent.
Arranging further is that described reaction is carried out at air balls.
Arrange further be reaction temperature be 110 DEG C, the response time is 24 hours.
It is an advantage of the invention that used alkali metal inorganic base can directly be commercially available.With literary composition The method of offering is compared, and this method can use cheap and easy to get, wide material sources, stablize low toxicity, green Alcohol compound is alkylating reagent, does not use any transition-metal catalyst and part, reaction Without inert gas shielding, can the most directly carry out, it is easy to operation, by-product is water, Environmental protection is pollution-free.Therefore, this method is relatively low to the requirement of reaction condition, the scope of application relatively Extensively, with the obvious advantage compared with known method, have and potential be widely applied prospect.
Below in conjunction with detailed description of the invention, the present invention is described further.
Detailed description of the invention
Below by embodiment, the present invention is specifically described, is served only for the present invention is carried out Further illustrate, it is impossible to be interpreted as limiting the scope of the present invention, the technical staff in this field The present invention is made some nonessential improvement and adjustment according to the content of foregoing invention by Cheng Shike.
Embodiment 1
1-(4-methoxyphenyl) ethanol and 4-methoxy benzyl alcohol prepare 1,3-bis-(4-methoxybenzene Base)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 4-methoxy benzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122 G, 100mol%), add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C Reaction 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates Yield 60%.1H NMR(500MHz,CDCl3): δ 7.93 (d, J=9.0Hz, 2H), 7.16 (d, J=8.5Hz, 2H), 6.91 (d, J=8.5Hz, 2H), 6.83 (d, J=9.0Hz, 2H), 3.85 (s, 3H), 3.77 (s, 3H), 3.20 (t, J=8.0Hz, 2H), 2.99 (t, J=8.0Hz, 2H).13C NMR(125.4MHz, CDCl3):δ198.0,163.4,158.0,133.5,130.3,130.1,129.4, 114.0,113.7,55.5,55.3,40.4.MS (EI): m/z (%) 271 (6), 270 (33),136(8),135(100),134(12),121(54),108(8),107(8), 92(8),77(19)。
Embodiment 2
1-(4-methoxyphenyl) ethanol and 2-thenyl alcohol prepare 1-(4-methoxyphenyl)-3-(2- Thienyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 2-thenyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 24%.1H NMR(500MHz,CDCl3):δ7.95-7.92(m,2H),7.11-7.10 (m,1H),6.93-6.90(m,3H),6.85-6.84(m,1H),3.85(s, 3H),3.32-3.25(m,4H).13C NMR(125.4MHz,CDCl3):δ197.1, 163.6,144.1,130.3,129.9,126.9,124.6,123.3,113.8,55.5, 40.2,24.4.MS (EI): m/z (%) 247 (5), 246 (26), 136 (9), 135 (100),111(5),110(9),107(9),97(10),92(9),77(16)。
Embodiment 3
1-(4-methoxyphenyl)-3-(2-prepared by 1-(4-methoxyphenyl) ethanol and 2-furancarbinol Furyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 2-furancarbinol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 14%.1H NMR(500MHz,CDCl3): δ 7.95 (d, J=8.5Hz, 2H), 7.30 (s, 1H), 6.92 (d, J=8.5Hz, 2H), 6.28 (s, 1H), 6.04 (s, 1H), 3.86 (s, 3H), 3.28 (t, J=7.5Hz, 2H), 3.07 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3):δ197.2,163.5, 155.0,141.1,130.3,129.9,113.8,110.2,105.3,55.5,36.6, 22.7.MS (EI): m/z (%) 230 (29), 137 (11), 136 (9), 135 (100), 134(6),107(12),94(11),92(9),81(12),77(18)。
Embodiment 4
1-(4-methoxyphenyl) ethanol and 1-naphthalene methanol prepare 1-(4-methoxyphenyl)-3-(1-naphthalene Base)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 1-naphthalene methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 69%.1H NMR(500MHz,CDCl3): δ 8.08 (d, J=8.0Hz, 1H), 7.95 (d, J=8.5Hz, 2H), 7.89 (d, J=8.0Hz, 1H), 7.77-7.75 (m,1H),7.56-7.50(m,2H),7.43-7.42(m,2H),6.92(d, J=8.5Hz, 2H), 3.87 (s, 3H), 3.55 (t, J=8.0Hz, 2H) 3.39 (t, J=8.0Hz, 2H).13C NMR(125.4MHz,CDCl3):δ197.9, 163.5,137.6,134.0,131.7,130.3,130.0,129.0,127.0,126.2, 126.1,125.7,125.6,123.6,113.7,55.5,39.4,27.4.MS(EI): M/z (%) 291 (7), 290 (32), 141 (15), 136 (9), 135 (100), 115 (7),105(7),92(5),77(11)。
Embodiment 5
1-(4-methoxyphenyl) ethanol and 2-fluorophenyl methanol prepare 1-(4-methoxyphenyl)-3-(2- Fluorophenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 2-fluorophenyl methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 23%.1H NMR(500MHz,CDCl3): δ 7.96 (d, J=9.0Hz, 2H), 7.29-7.26(m,1H),7.22-7.18(m,1H),7.09-7.02(m,2H), 6.93 (d, J=9.0Hz, 2H), 3.87 (s, 3H), 3.26 (t, J=7.5 Hz, 2H), 3.09 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3): δ197.6,163.4,161.3(d,JC-F=243.8Hz), 130.9 (d, JC-F= 5.0Hz),130.3,129.9,128.2(d,JC-F=15.0Hz), 127.9 (d, JC-F=8.8Hz), 124.1 (d, JC-F=3.8Hz), 115.3 (d, JC-F=22.5 Hz),113.8,55.5,38.5(d,JC-F=1.2Hz), 24.1 (d, JC-F=2.5 Hz) .MS (EI): m/z (%) 259 (5), 258 (28), 136 (9), 135 (100), 121(3),109(4),107(9),92(7),77(13),64(3)。
Embodiment 6
1-(4-methoxyphenyl) ethanol and 2-methoxy benzyl alcohol prepare 1-(4-methoxybenzene Base)-3-(2-methoxyphenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 2-methoxy benzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122 G, 100mol%), add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C Reaction 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates Yield 63%.1H NMR(500MHz,CDCl3): δ 7.99 (d, J=9.0Hz, 2H),7.24-7.21(m,2H),6.95-6.87(m,4H),3.88(s,3H), 3.85 (s, 3H), 3.23 (t, J=7.5Hz, 2H), 3.06 (t, J=7.5 Hz,2H).13C NMR(125MHz,CDCl3):δ198.6,163.4,157.6,130.4, 130.2,130.1,129.7,127.5,120.6,113.7,110.3,55.5,55.2, 38.7,26.0.MS (EI): m/z (%) 271 (5), 270 (24), 136 (9), 135(100),134(10),107(7),105(3),92(8),91(4),77(13)。
Embodiment 7
1-(4-methoxyphenyl) ethanol and 2-chlorobenzene methanol prepare 1-(4-methoxyphenyl)-3-(2- Chlorphenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 2-chlorobenzene methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 74%.1H NMR(500MHz,CDCl3): δ 7.94 (d, J=8.5Hz, 2H), 7.35-7.28 (m, 2H), 7.19-7.12 (m, 2H), 6.90 (d, d, J=9.0 Hz,2H),3.84(s,3H),3.26-3.21(m,2H),3.18-3.14(m, 2H).13C NMR(125MHz,CDCl3):δ197.6,163.5,139.0,134.0, 130.8,130.3,130.0,129.6,127.7,127.0,113.8,55.5,38.1, 28.6.MS (EI): m/z (%) 240 (13), 239 (74), 136 (9), 135 (100), 107(12),103(4),92(12),77(22),64(5),63(3)。
Embodiment 8
1-(4-methoxyphenyl) ethanol and 2-bromobenzene methanol prepare 1-(4-methoxyphenyl)-3-(2- Bromophenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 2-bromobenzene methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C of reactions 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, separation yield 65%.1H NMR(500MHz,CDCl3): δ 7.86 (d, J=8.0Hz, 2H), 7.45 (d, J=8.0Hz, 1H), 7.22 (d, J=8.0Hz, 1H), 7.17-7.13 (m, 1H), 6.99-6.96 (m, 1H), 6.83 (d, J=8.0Hz, 2H), 3.76 (s, 3H), 3.16 (t, J=7.5Hz, 2H), 3.07 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3):δ197.5,163.5,140.7,132.9,130.8, 129.9,127.9,127.6,124.4,113.8,55.5,38.3,31.0.MS(EI): M/z (%) 319 (1), 240 (18), 239 (100), 136 (8), 135 (94), 121 (5),119(4),107(11),92(10),77(20),64(4)。
Embodiment 9
1-(4-methoxyphenyl) ethanol and 3-methylbenzyl alcohol prepare 1-(4-methoxybenzene Base)-3-(3-aminomethyl phenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 3-methylbenzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 75%.1H NMR(500MHz,CDCl3): δ 7.97 (d, J=9.0Hz, 2H), 7.21 (t, J=7.5Hz, 1H), 7.09-7.04 (m, 3H), 6.94 (d, J =9.0Hz, 2H), 3.88 (s, 3H), 3.26 (t, J=8.0Hz, 1H), 3.04 (t, J=8.0Hz, 1H), 2.36 (s, 3H).13C NMR(125.4MHz,CDCl3): δ197.9,163.5,141.4,138.1,130.3,130.0,129.3,128.4, 126.8,125.4,113.7,55.5,40.2,30.3,21.4.MS (EI): m/z (%) 255(6),254(33),136(9),135(100),118(3),107(7),105 (3),92(6),77(13)。
Embodiment 10
1-(4-methoxyphenyl) ethanol and 3-methoxy benzyl alcohol prepare 1-(4-methoxybenzene Base)-3-(3-methoxyphenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 3-methoxy benzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122 G, 100mol%), add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C Reaction 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates Yield 59%.1H NMR(500MHz,CDCl3): δ 7.93 (d, J=7.5Hz, 2H), 7.21-7.19 (m, 1H), 7.91 (d, J=7.5Hz, 2H), 6.84-6.80 (m, 2H), 6.75-6.73 (m, 1), 3.84 (t, J=7.5Hz, 2H), 3.78 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3):δ197.8,163.5, 159.8,143.1,130.3,130.0,129.5,120.8,114.3,113.8,111.4, 55.5,55.2,40.0,30.4.MS (EI): m/z (%) 271 (5), 270 (26), 252 (7),136(9),135(100),121(12),107(9),92(7),91(10), 77(13)。
Embodiment 11
1-(4-methoxyphenyl) ethanol and 3-fluorophenyl methanol prepare 1-(4-methoxyphenyl)-3-(3- Fluorophenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 3-fluorophenyl methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 69%.1H NMR(500MHz,CDCl3): δ 7.94 (d, J=9.0Hz, 2H), 7.26-7.22 (m, 1H), 7.02 (d, J=7.5Hz, 2H), 6.96-6.86 (m, 4H), 3.86 (s, 3H), 3.24 (t, J=7.5Hz, 2H), 3.05 (t, J =7.5Hz, 2H).13C NMR(125.4MHz,CDCl3):δ197.4,163.9,163.5, 161.9,144.0(d,JC-F=7.5Hz), 130.3,129.9 (d, JC-F=8.8 Hz),124.1,115.3(d,JC-F=21.2Hz), 113.8,112.9 (d, JC-F =21.2Hz), 55.5,39.6,29.9.
Embodiment 12
1-(4-methoxyphenyl) ethanol and 3-chlorobenzene methanol prepare 1-(4-methoxyphenyl)-3-(3- Chlorphenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 3-chlorobenzene methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 62%.1H NMR(500MHz,CDCl3): δ 7.91 (d, J=9.0Hz, 2H), 7.22-7.10 (m, 4H), 6.90 (d, J=9.0Hz, 2H), 3.83 (s, 3H), 3.20 (t, J=7.5Hz, 2H), 3.01 (t, J=7.5Hz, 2H).13C NMR (125.4MHz,CDCl3):δ197.2,163.6,143.6,134.2,130.3,129.9, 129.8,128.6,126.8,113.8,55.5,39.6,29.9.MS (EI): m/z (%) 240(14),239(83),136(9),135(100),125(3),107(10),103 (3),92(9),77(17),64(4)。
Embodiment 13
1-(4-methoxyphenyl) ethanol and 3-bromobenzene methanol prepare 1-(4-methoxyphenyl)-3-(3- Bromophenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 3-bromobenzene methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 63%.1H NMR(500MHz,CDCl3): δ 7.92 (d, J=9.0Hz, 2H), 7.40(s,1H),7.33-7.31(m,1H),7.18-7.12(m,2H),6.91 (d, J=9.0Hz, 2H), 3.85 (s, 3H), 3.22 (t, J=7.5Hz, 2H), 3.01 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3): δ197.2,163.6,143.9,131.5,130.3,130.1,129.8,129.2, 127.2,122.5,113.8,55.5,39.7,29.8.MS (EI): m/z (%) 320 (3), 319(14),318(3),317(14),136(9),135(100),107(7),92 (6),77(12),64(13)。
Embodiment 14
1-(4-methoxyphenyl) ethanol and 4-fluorophenyl methanol prepare 1-(4-methoxyphenyl)-3-(4- Fluorophenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 4-fluorophenyl methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 55%.1H NMR(500MHz,CDCl3): δ 7.94 (d, J=9.0Hz, 2H), 7.23-7.20 (m, 2H), 7.00-6.96 (m, 2H), 6.93 (d, J=9.0Hz, 2H), 3.87 (s, 3H), 3.23 (t, J=7.5Hz, 2H), 3.04 (t, J =7.5Hz, 2H).13C NMR(125.4MHz,CDCl3):δ197.6,163.5,161.4 (d,JC-F=242.5Hz), 137.1 (d, JC-F=2.5Hz), 130.3,129.9, 129.8(d,JC-F=7.5Hz), 115.2 (d, JC-F=21.25Hz), 113.8, 55.5,40.1,29.5.MS (EI): m/z (%) 259 (5), 258 (29), 136 (9), 135(100),121(4),109(6),108(4),107(9),92(7),77(12)。
Embodiment 15
1-(4-methoxyphenyl) ethanol and 4-chlorobenzene methanol prepare 1-(4-methoxyphenyl)-3-(4- Chlorphenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 4-chlorobenzene methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 74%.1H NMR(500MHz,CDCl3): δ 7.83 (d, J=8.5Hz, 2H), 7.15 (d, J=8.5Hz, 2H), 7.08 (d, J=8.0Hz, 2H), 6.82 (d, J=9.0Hz, 2H), 3.76 (s, 3H), 3.12 (t, J=7.5Hz, 2H), 2.92 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3): δ197.4,163.5,140.0,131.8,130.3,129.9,128.6,113.8,55.5, 39.8,29.6.MS (EI): m/z (%) 240 (13), 239 (81), 136 (9), 135 (100),107(11),103(5),92(11),77(18),64(5)。
Embodiment 16
1-(4-methoxyphenyl) ethanol and 4-bromobenzene methanol prepare 1-(4-methoxyphenyl)-3-(4- Bromophenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 4-bromobenzene methanol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 82%.1H NMR(500MHz,CDCl3): δ 7.84 (d, J=8.5Hz, 2H), 7.31 (d, J=8.0Hz, 2H), 7.04 (d, J=8.5Hz, 2H), 6.83 (d, J=9.0Hz, 2H), 3.77 (s, 3H), 3.14 (t, J=7.5Hz, 2H), 2.92 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3): δ197.4,163.6,140.5,131.5,130.3,130.2,129.9,119.8, 113.8,55.5,39.7,29.6.MS (EI): m/z (%) 319 (13), 317 (15), 136(8),135(100),109(6),107(8),92(7),77(14),64(8)。
Embodiment 17
1-(4-methoxyphenyl) ethanol and 4-methylbenzyl alcohol prepare 1-(4-methoxybenzene Base)-3-(4-aminomethyl phenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-methoxyphenyl) ethanol (0.3042g, 2 Mmol), 4-methylbenzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), add toluene 4mL, be heated to 110 DEG C under the conditions of tube sealing fresh air ball instead Answer 24h.TLC and GC-MS monitors reaction, and product pillar layer separation purifies, and separates and receives Rate 52%.1H NMR(500MHz,CDCl3): δ 7.93 (d, J=9.0Hz, 2H), 7.14 (d, J=8.0Hz, 2H), 7.10 (d, J=8.0Hz, 2H), 6.90 (d, J=9.0Hz, 2H), 3.84 (s, 3H), 3.21 (t, J=7.5Hz, 2H), 3.00 (t, J=7.5Hz, 2H), 2.31 (s, 3H).13C NMR(125.4 MHz,CDCl3):δ197.9,163.5,138.4,135.6,130.3,130.0,129.2, 128.3,113.8,55.5,40.3,30.0,21.0.MS (EI): m/z (%) 255 (5),254(27),136(9),135(100),121(4),118(6),107(8), 105(6),92(7),77(13)。
Embodiment 18
1-(4-chlorphenyl) ethanol and 4-methoxy benzyl alcohol prepare 1-(4-chlorphenyl)-3-(4-methoxy Base phenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-chlorphenyl) ethanol (0.3121g, 2mmol), 4-methoxy benzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100 Mol%), add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C of reaction 24h. TLC and GC-MS monitors reaction, and product pillar layer separation purifies, separation yield 40%.1H NMR(500MHz,CDCl3): δ 7.90 (d, J=8.5Hz, 2H), 7.43 (d, J=8.5Hz, 2H), 7.17 (d, J=8.5Hz, 2H), 6.86 (d, J=8.5 Hz, 2H), 3.80 (s, 3H), 3.25 (t, J=7.5Hz, 2H), 3.02 (t, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3):δ198.2,158.1, 139.5,135.2,133.1,129.5,129.4,128.9,114.0,55.3,40.7, 29.2.MS (EI): m/z (%) 276 (12), 274 (35), 141 (8), 139 (24), 135(12),122(9),121(100),111(12),108(17),77(7)。
Embodiment 19
1-(4-fluorophenyl) ethanol and 4-methoxy benzyl alcohol prepare 1-(4-fluorophenyl)-3-(4-methoxy Base phenyl)-1-acetone
Tubular reactor is sequentially added into 1-(4-fluorophenyl) ethanol (0.2802g, 2mmol), 4-methoxy benzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100 Mol%), add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C of reaction 24h. TLC and GC-MS monitors reaction, and product pillar layer separation purifies, separation yield 17%.1H NMR (500MHz,CDCl3):δ8.00-7.98(m,2H),7.19-7.17(m,2H), 7.14-7.11(m,2H),6.86-6.85(m,2H),3.80(s,3H),3.25 (t, J=7.5Hz, 2H), 3.02 (t, J=7.5Hz, 2H).13C NMR(125.4 MHz,CDCl3):δ197.8,165.7(d,JC-F=253.8Hz) 158.0,133.4 (d,JC-F=3.8Hz), 133.2,130.7 (d, JC-F=8.8Hz), 129.4, 115.7(d,JC-F=21.2Hz), 114.0,55.3,40.6,29.3.MS (EI): M/z (%) 259 (9), 258 (52), 135 (13), 123 (34), 122 (10), 121 (100),108(18),95(20),91(7),77(7)。
Embodiment 20
1-phenylethanol and 4-methoxy benzyl alcohol prepare 1-phenyl-3-(4-methoxyphenyl)-1-third Ketone
Tubular reactor is sequentially added into 1-phenylethanol (0.2442g, 2mmol), 4-first Epoxide benzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), Add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C of reaction 24h.TLC With GC-MS monitoring reaction, product pillar layer separation purifies, separation yield 43%.1H NMR (500MHz,CDCl3): δ 7.85 (d, J=7.5Hz, 2H), 7.45-7.42 (m, 1H), 7.35-7.32 (m, 2H), 7.07 (d, J=8.5Hz, 2H), 6.74 (d, J=8.5Hz, 2H), 3.67 (s, 3H), 3.16 (d, J=7.5Hz, 2H), 2.91 (d, J=7.5Hz, 2H).13C NMR(125.4MHz,CDCl3):δ198.3, 156.9,135.8,132.2,132.0,128.3,127.5,127.0,112.9,54.2, 39.6,28.2.MS (EI): m/z (%) 241 (9), 240 (49), 135 (14), 122 (9),121(100),108(18),105(42),91(7),78(6),77(30)。
Embodiment 21
1-tetralol and 4-methoxy benzyl alcohol prepare 2-(4-methoxyphenyl)-ALPHA-tetralone
Tubular reactor is sequentially added into 1-tetralol (0.2962g, 2mmol), 4-first Epoxide benzyl alcohol (3mmol, 1.5equiv.) and potassium hydroxide (0.1122g, 100mol%), Add toluene 4mL, under the conditions of tube sealing fresh air ball, be heated to 110 DEG C of reaction 24h.TLC With GC-MS monitoring reaction, product pillar layer separation purifies, separation yield 33%.1H NMR (500MHz,CDCl3): δ 8.06 (d, J=8.0Hz, 1H), 7.46 (t, J =7.5Hz, 1H), 7.31 (t, J=7.5Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 7.14 (d, J=8.5Hz, 2H), 6.85 (d, J=8.5Hz, 2H), 3.79 (s, 3H), 3.40 (dd, J=13.5Hz, J=4.0Hz, 1H), 2.99-2.88 (m, 2H), 2.73-2.67 (m, 2H), 2.62 (dd, J=14.0Hz, J=9.5 Hz,1H),2.14-2.08(m,1H),1.82-1.74(m,1H).13C NMR(125.4 MHz,CDCl3):δ199.6,158.0,144.1,133.3,130.2,128.7,127.6, 126.6,113.8,55.3,49.6,34.8,28.6,27.6.MS (EI): m/z (%) 266(17),122(10),121(100),108(13),91(6),77(6)。

Claims (9)

1. the method that the preparation of secondary alcohol oxidation dewatering alkylation replaces ketone compounds, its feature exists In:
Primary alconol and secondary alcohol alkali metal inorganic base and at air conditions under, with the oxygen in air be Oxidant directly carries out dewatering alkylation-oxidation reaction and obtains replacing ketone compounds, reaction Temperature is 100～130 DEG C, and the response time is 12-60 hour, and by-product is water, reaction Formula is:
A kind of secondary alcohol oxidation dewatering alkylation preparation the most according to claim 1 replaces ketone The method of compound, it is characterised in that: in secondary alcohol, R1Be H or various group be substituted in 2-, The phenyl of 3-, 4-position or other aryl, polysubstituted phenyl or other aryl；Or Person R1It is various carbon chain lengths and the fatty alkyl of substitution in side chain or naphthane alcohols knot The secondary alcohol of structure.
A kind of secondary alcohol oxidation dewatering alkylation preparation the most according to claim 1 replaces ketone The method of compound, it is characterised in that: in primary alconol, R2It is that phenyl, various group are substituted in The phenyl of 2-, 3-, 4-position or other aryl, polysubstituted phenyl or other aryl Or substituted heteroaryl.
A kind of secondary alcohol oxidation dewatering alkylation preparation the most according to claim 1 replaces ketone The method of compound, it is characterised in that: alkali metal inorganic base is NaOH, KOH or CsOH.
5. aoxidize dewatering alkylation preparation according to a kind of secondary alcohol described in claim 1 or 4 and replace ketone The method of compounds, it is characterised in that: the consumption of alkali metal inorganic base is 50～200 Mol%.
A kind of secondary alcohol oxidation dewatering alkylation preparation the most according to claim 1 replaces ketone The method of compound, it is characterised in that: reaction in organic solvent or is entered under condition of no solvent OK.
A kind of secondary alcohol oxidation dewatering alkylation preparation the most according to claim 1 replaces ketone The method of compound, it is characterised in that: reaction is carried out using toluene as solvent.
A kind of secondary alcohol oxidation dewatering alkylation preparation the most according to claim 1 replaces ketone The method of compound, it is characterised in that: described reaction uses air balls to carry out under air.
A kind of secondary alcohol oxidation dewatering alkylation preparation the most according to claim 1 replaces ketone The method of compound, it is characterised in that: reaction temperature is 110 DEG C, and the response time is 24 little Time.
CN201610381667.XA 2016-06-01 2016-06-01 Method for preparing substituted ketone compound through oxidization, dehydration and alkylation of secondary alcohol Pending CN105884603A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112569936A (en) * 2020-12-14 2021-03-30 江南大学 Novel metal-doped catalyst for selectively synthesizing bisphenol F, and preparation method and application thereof
CN113480394A (en) * 2021-07-05 2021-10-08 温州大学 Green synthesis method of alkylene fluorene

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LAURA J. ET AL: "Green alcohol couplings without transition metal catalysts:base-mediated β-alkylation of alcohols in aerobic conditions", 《GREEN CHEMISTY》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112569936A (en) * 2020-12-14 2021-03-30 江南大学 Novel metal-doped catalyst for selectively synthesizing bisphenol F, and preparation method and application thereof
CN112569936B (en) * 2020-12-14 2022-04-15 江南大学 Novel metal-doped catalyst for selectively synthesizing bisphenol F, and preparation method and application thereof
CN113480394A (en) * 2021-07-05 2021-10-08 温州大学 Green synthesis method of alkylene fluorene

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