CN105085463B - A kind of microwave quickly prepares seven yuan of methods of lactone of biaryl - Google Patents
A kind of microwave quickly prepares seven yuan of methods of lactone of biaryl Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
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Abstract
Seven yuan of methods of lactone of biaryl are quickly prepared the invention provides a kind of microwave, it comprises the following steps：Step A：With compound 1 as reactant, with dissolved oxygen acetonitrile as solvent, with N heterocycle carbines as catalyst, there is pole reversal reaction under the microwave of 700 900W and in 25 80 DEG C of environment, obtain crude product, step B：Seven yuan of lactones of biaryl are extracted from the crude product；That is compound 2.The reaction equation of above-mentioned reaction is：
Description
Technical field
The present invention relates to organic synthesis field, seven yuan of lactones of biaryl are quickly prepared in particular to a kind of microwave
Method.
Background technology
Seven yuan of lactones of biaryl are a kind of bioactive compounds with antiarrhythmic activity, and it is also much many work(
The important feature part of energy epoxy resin, the constituent for be various adhesives, fluid sealant, covering glue is some chemical products
Necessary raw material.Existing many document reports in recent years, seven yuan of lactones of biaryl have various synthetic methods, including biaryl glycol or
The oxidation of person's dialdehyde lactonizes, the oxidation scission of biaryl alkene, the reduction of biaryl dicarboxylic acids etc., such as reaction equation ().
There is following technological deficiency in these synthetic methods：Need to be with valuable rare or be difficult to metallic catalyst, the toxicity/severe corrosive for preparing
Reagent, course of reaction is seriously polluted, and severe reaction conditions (anhydrous and oxygen-free, pressurization, for a long time high temperature, reaction etc.) and post processing are numerous
Trivial and yield is low.Even the intramolecular coupling method of Gerhard B reports, it is also desirable to urged with nickel composite and triphenyl phosphorus
Change and need butyl lithium reagent to participate in.
Reaction equation (one)
The organic catalytic reaction of polarity inversion has broken the understanding for synthon reactivity worth in traditional sense, opens
One approach that carbon-carbon bond is built with unorthodox method, is used for changing the conventional side of popular response pattern as organic chemist
Method.With the intensification understood polarity inversion mechanism, polarity inversion catalyst is increasingly developed, applies, and cyanide is acute due to it
The application that malicious characteristic is faded out in polarity inversion organic catalysis gradually, N- heterocycle carbines (NHCs) are unique due to its, species
The advantages of various and smaller toxicity and turn into one of the most frequently used organic micromolecule catalyst in such reaction.Having been reported will
The pole reversal reaction of NHCs effects is used to synthesize seven yuan of lactones of biaryl, although which overcomes many of prior synthesizing method and lacks
Fall into, also obtain yield higher, but still suffer from significant limitation, such as reaction time is long, at least needs 3h so that its
Using being restricted.
In view of this, it is special to propose the present invention.
The content of the invention
Seven yuan of methods of lactone of biaryl are quickly prepared it is an object of the invention to provide a kind of microwave, the method is in microwave
The lower reaction rate of radiation is fast, seven yuan of lactones of biaryl that yield is more than 85% can be obtained at most in 60min, with production
The advantages of efficiency high, process is simple.
In order to realize above-mentioned purpose of the invention, spy uses following technical scheme：
A kind of microwave quickly prepares seven yuan of methods of lactone of biaryl, comprises the following steps：
Step A：With compound 1 as reactant, with dissolved oxygen acetonitrile as solvent, with N- heterocycle carbines as catalyst, in 700-
There is pole reversal reaction under the microwave of 900W and in 25-80 DEG C of environment, obtain crude product, reaction equation is as follows：
Reaction equation (two)；
R, R ' separately selected from the one kind in following：Halogen, nitro, methyl, methoxyl group and phenyl ring have two altogether
The phenyl of same carbon atom；X is halogen；
Step B：Seven yuan of lactones of biaryl are extracted from the crude product；That is compound 2.
The reaction principle of above-mentioned preparation method is：In the presence of dissolved oxygen acetonitrile and N- heterocycle carbines occur polarity inversion and
Oxidation reaction, generates seven yuan of lactones of biaryl.Because the reaction is microwave and the 25-80 DEG C of condition generation in 700-900W
, therefore compared to traditional pole reversal reaction, reaction rate is greatly improved, and yield higher still can be obtained,
Yield can at least reach 85% in 60min.
In addition, from said process, preparation method of the invention only needs single step reaction to can be prepared by product, and need not
Harsh operating condition, therefore there is process is simple, easy to operate.
Preferably, the feed postition of the N- heterocycle carbines is：Add alkali and N- heterocycle carbine thiazole salts.
The property of free N- heterocycle carbines is unstable, adds alkali and N- heterocycle carbine thiazole salts, is now given birth in reaction system
Into N- heterocycle carbines, reaction effect can be improved.
Preferably, the alkali is the mixture of DBU and potassium carbonate, adds DBU to improve seven yuan of products of lactone of biaryl
Rate.
Preferably, reaction temperature is 50-80 DEG C, and in this temperature range, reaction rate is faster.In addition, at this temperature,
Yield basically reaches peak in 15min.
Preferably, the mol ratio of potassium carbonate and N- heterocycle carbine thiazole salts is：1.8-2：1；It is high using this ratio yield, also
20-25 μ L DBU can be added in further preferably every 1mmol potassium carbonate.
Preferably, the N- heterocycle carbines are 3,4,5- trimethylthiazoles, compared to other types of N- heterocycle carbines, 3,4,
Yield is higher when 5- trimethylthiazoles are catalyzed.
Preferably, the N- heterocycle carbines and compound 1 are equimolar addition.When rubbing for N- heterocycle carbines and compound 1
You reach 1 by ratio:Yield basically reaches maximum when 1.
Preferably, the method for the extraction is：It is 1 with volume ratio:The ethyl acetate/petroleum ether of 35-40 is mobile phase, is entered
Row column chromatography；Seven yuan of lactones of biaryl of high-purity can be within a short period of time extracted using column chromatography.In order to improve post layer
The efficiency of analysis, can be pre-processed, for example, before the column chromatography, first filtering, concentrating.
Preferably, the pole reversal reaction is carried out in Microwave-assisted synthesis/extractive reaction instrument.Give birth in this device
Product is safe, easy to operate, and available Microwave-assisted synthesis/extractive reaction instrument is：The new instrument MAS-I type normal pressure microwaves of SINEO
Auxiliary synthesis/extractive reaction instrument.
Compared with prior art, beneficial effects of the present invention are：
(1) both overcome that expensive reagents existing for prior synthesizing method, toxicity/corrosivity is strong, seriously polluted, condition is severe
The shortcomings of quarter, preferable reaction speed and yield are obtained again, also there is process is simple, easy to operate.
(2) applied widely, preparation method of the invention is adapted to prepare seven yuan of lactone compounds of most aryl.
(3) short this advantage reaction time is especially protruded, and compared to existing advanced synthetic method, the time at least shortens
67%, and the yield of phase same level can also be reached.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the present invention.It is unreceipted specific in embodiment
Condition person, the condition advised according to normal condition or manufacturer is carried out.Agents useful for same or the unreceipted production firm person of instrument, are
The conventional products that can be obtained by commercially available purchase.
Hereafter the pole reversal reaction of all embodiments is in the new instrument MAS-I types normal pressure microwave auxiliary synthesis/extractions of SINEO
Carried out in reaction instrument.
Embodiment 1 biphenyl [c, e] oxa-The synthetic method one of -5 (7H) -one 2a：
Reaction equation (three)
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 50 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 41mg are separated to obtain, yield is 98%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 2 biphenyl [c, e] oxa-The synthesis synthetic method two of -5 (7H) -one 2a：
Reaction equation (four)
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt II 63mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 50 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 38mg are separated to obtain, yield is 90%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 3 biphenyl [c, e] oxa-The synthesis synthetic method three of -5 (7H) -one 2a：
Reaction equation (five)
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt III 48mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add
3mL dries dissolved oxygen acetonitrile, and stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature to set Microwave-assisted synthesis reaction instrument
50 DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 39mg are separated to obtain, yield is 92%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 4 biphenyl [c, e] oxa-The synthetic method four of -5 (7H) -one 2a：
Reaction equation (six)
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dry dissolved oxygen acetonitrile.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.Reaction
After end, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) separate
Product 2a 12mg, yield is 30%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 5 biphenyl [c, e] oxa-The synthetic method five of -5 (7H) -one 2a：
Reaction equation is with embodiment 1.
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 25 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 31mg are separated to obtain, yield is 74%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 6 biphenyl [c, e] oxa-The synthetic method six of -5 (7H) -one 2a：
Reaction equation is with embodiment 1.
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 25 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 30min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 34mg are separated to obtain, yield is 81%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 7 biphenyl [c, e] oxa-The synthetic method seven of -5 (7H) -one 2a：
Reaction equation is with embodiment 1.
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 25 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 60min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 36mg are separated to obtain, yield is 85%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 8 biphenyl [c, e] oxa-The synthetic method eight of -5 (7H) -one 2a：
Reaction equation is with embodiment 1.
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 75 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 40mg are separated to obtain, yield is 95%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 9 biphenyl [c, e] oxa-The synthetic method nine of -5 (7H) -one 2a：
Reaction equation is with embodiment 1.
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 700W, reaction temperature 50 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 38mg are separated to obtain, yield is 90%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 10 biphenyl [c, e] oxa-The synthetic method ten of -5 (7H) -one 2a：
Reaction equation is with embodiment 1.
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.16mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 50 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：40) product 2a 33mg are separated to obtain, yield is 78%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 11 biphenyl [c, e] oxa-The synthetic method 11 of -5 (7H) -one 2a：
Reaction equation is with embodiment 1.
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 10.It is power 900W, reaction temperature 50 to set Microwave-assisted synthesis reaction instrument
DEG C, reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (acetic acid second
Ester：Petroleum ether=1：35) product 2a 41mg are separated to obtain, yield is 98%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 12 biphenyl [c, e] oxa-The synthetic method 12 of -5 (7H) -one 2a：
Reaction equation (seven)
To dry microwave reaction bottle in sequentially add 2 '-(chloromethyl) xenyl -2- formaldehyde (1a ') 46mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), add 3mL
Dissolved oxygen acetonitrile (being prepared according to the description in the content of the invention) is dried, stirring is lower to add the μ L of DBU 10.Setting microwave radiation technology is closed
It is power 900W, 50 DEG C of reaction temperature, reaction time 15min into reaction instrument.After reaction terminates, reaction solution suction filtration, filtrate is revolving
Turn evaporimeter concentration, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2a 37mg are separated to obtain, yield is 88%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 13 biphenyl [c, e] oxa-The synthetic method 13 of -5 (7H) -one 2a：
To dry microwave reaction bottle in sequentially add 2 '-(bromomethyl) xenyl -2- formaldehyde (1a) 55mg
(0.2mmol), N- heterocycle carbines thiazole salt I 51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.36mmol), add 3mL
Dissolved oxygen acetonitrile is dried, stirring is lower to add the μ L of DBU 7.It is power 900W to set Microwave-assisted synthesis reaction instrument, 50 DEG C of reaction temperature,
Reaction time 15min.After reaction terminates, reaction solution suction filtration, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Stone
Oily ether=1：40) product 2a 36mg are separated to obtain, yield is 85%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.880 (dd, J=7.0,1.5Hz, 1H), 7.796-
7.732 (m, 3H), 7.652-7.600 (m, 3H), 7.512 (td, J=6.0,1.0Hz, 1H), 5.128 (d, J=9.0Hz, 1H),
5.023 (d, J=9.0Hz, 1H) .LRMS:[M]+,210.07。
Embodiment 14 3- bromobiphenyls [c, e] oxa-The synthesis of -5 (7H) -one 2b：
Reaction equation (eight)
To dry microwave reaction bottle in sequentially add compound 1b 70mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2b is separated to obtain
48mg, yield is 83%.
To the sign of product：1H NMR (500MHz, DMSO) δ 8.002 (d, J=8.0Hz, 1H), 7.837-7.772 (m,
3H), (d, J=9.0Hz, the 1H) .LRMS of 7.478-7.432 (m, 3H), 5.510 (d, J=9.0Hz, 1H), 5.488:[M]+,
287.98。
Embodiment 15 9- bromobiphenyls [c, e] oxa-The synthesis of -5 (7H) -one 2c：
Reaction equation (nine)
To dry microwave reaction bottle in sequentially add compound 1c 70mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2c is separated to obtain
46mg, yield is 80%.
To the sign of product：1H NMR (500MHz, DMSO) δ 8.452 (d, J=8.0Hz, 1H), 7.696-7.540 (m,
6H), 5.512 (d, J=9.0Hz, 1H), 5.450 (d, J=9.0Hz, 1H) .LRMS:[M]+,287.98。
Embodiment 16 3,9- bis- bromobiphenyl [c, e] oxa-The synthesis of -5 (7H) -one 2d：
Reaction equation (ten)
To dry microwave reaction bottle in sequentially add compound 1d 86mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2d is separated to obtain
53mg, yield is 72%.
To the sign of product：1H NMR (500MHz, DMSO) δ 8.382 (d, J=7.0Hz, 1H), 7.836-7.596 (m,
6H), 5.502 (d, J=9.0Hz, 1H), 5.432 (d, J=9.0Hz, 1H) .LRMS:[M]+,367.89。
Embodiment 17 3,9- dinitros biphenyl [c, e] oxa-The synthesis of -5 (7H) -one 2e：
Reaction equation (11)
To dry microwave reaction bottle in sequentially add compound 1e 73mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2e is separated to obtain
42mg, yield is 70%.
To the sign of product：1H NMR(500MHz,DMSO)δ8.410(s,1H),8.309-8.238(m,3H),8.058
(d, J=7.5Hz, 1H), 7.612 (d, J=7.5Hz, 1H), 5.366 (d, J=9.0Hz, 1H), 5.272 (d, J=9.0Hz,
1H).LRMS:[M]+,300.04。
Embodiment 18 3,9- dimethoxy-biphenyls [c, e] oxa-The synthesis of -5 (7H) -one 2f：
Reaction equation (12)
To dry microwave reaction bottle in sequentially add compound 1f 67mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2f is separated to obtain
39mg, yield is 73%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.886-7.702 (m, 3H), 7.235 (dd, J=7.5,
1.5Hz, 1H), 7.122 (d, J=1.5Hz, 1H), 7.004 (dd, J=7.5,1.5Hz, 1H), 5.174 (d, J=9.0Hz,
1H), (s, the 3H) .LRMS of 5.072 (d, J=9.0Hz, 1H), 4.092 (s, 3H), 4.020:[M]+,270.09。
Embodiment 19 3,9- dimethyl diphenyls [c, e] oxa-The synthesis of -5 (7H) -one 2g：
Reaction equation (13)
To dry microwave reaction bottle in sequentially add compound 1g 61mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2g is separated to obtain
33mg, yield is 68%.
To the sign of product：1H NMR(500MHz,DMSO)δ7.677-7.620(m,3H),7.412-7.388(m,3H),
(s, the 3H) .LRMS of 5.064 (d, J=9.0Hz, 1H), 4.922 (d, J=9.0Hz, 1H), 2.414 (s, 3H), 2.396:[M]+,
238.10。
Embodiment 20 3,10- dimethoxy-biphenyls [c, e] oxa-The synthesis of -5 (7H) -one 2h
Reaction equation (14)
To dry microwave reaction bottle in sequentially add compound 1h 67mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2h is separated to obtain
43mg, yield is 80%.
To the sign of product：1H NMR (500MHz, DMSO) δ 7.844-7.682 (m, 3H), 7.244 (dd, J=7.5,
1.5Hz, 1H), 7.129 (d, J=1.5Hz, 1H), 7.016 (dd, J=7.5,1.5Hz, 1H), 5.524 (d, J=9.0Hz,
1H), (s, the 3H) .LRMS of 5.432 (d, J=9.0Hz, 1H), 3.832 (s, 3H), 3.770:[M]+,270.09。
Embodiment 21 3,10- dimethyl diphenyls [c, e] oxa-The synthesis of -5 (7H) -one 2i：
Reaction equation (15)
To dry microwave reaction bottle in sequentially add compound 1g 61mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2g is separated to obtain
35mg, yield is 74%.
To the sign of product：1H NMR(500MHz,DMSO)δ7.676-7.618(m,3H),7.453-7.378(m,3H),
(s, the 3H) .LRMS of 5.062 (d, J=9.0Hz, 1H), 4.919 (d, J=9.0Hz, 1H), 2.463 (s, 3H), 2.426:[M]+,
238.10。
Dinaphthyl [the 2,1-c of embodiment 22:1', 2'-e] oxa-The synthesis of -3 (5H) -one 2j：
Reaction equation (16)
To dry microwave reaction bottle in sequentially add compound 1j 75mg (0.2mmol), N- heterocycle carbine thiazole salts I
51mg (0.2mmol) and Anhydrous potassium carbonate 55mg (0.4mmol), adds 3mL and dries dissolved oxygen acetonitrile, and stirring is lower to add DBU 10
μL.It is power 900W, 50 DEG C of reaction temperature, reaction time 15min to set Microwave-assisted synthesis reaction instrument.After reaction terminates, instead
Liquid suction filtration is answered, filtrate is concentrated with Rotary Evaporators, preparative chromatography (ethyl acetate：Petroleum ether=1：40) product 2j is separated to obtain
53mg, yield is 85%.
To the sign of product：1H NMR (500MHz, DMSO) δ 8.225 (d, J=8.0Hz, 1H), 7.966 (d, J=
8.0Hz,1H),7.651-7.597(m,3H),7.363-7.314(m,5H),7.117-7.102(m,1H),6.992-6.977
(m, 1H), 5.238 (d, J=9.0Hz, 1H), 5.123 (d, J=9.0Hz, 1H) .LRMS:[M]+,310.10。
Although illustrate and describing the present invention with specific embodiment, but will be appreciated that without departing substantially from of the invention
Many other changes and modification can be made in the case of spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (9)
1. a kind of microwave quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that comprise the following steps：
Step A：With compound 1 as reactant, with dissolved oxygen acetonitrile as solvent, with N- heterocycle carbines as catalyst, in 700-900W
Microwave under and 25-80 DEG C of environment in there is pole reversal reaction, react 15-60min, obtain crude product, react
Formula is as follows：
R, R ' separately selected from the one kind in following：Halogen, nitro, methyl, methoxyl group and phenyl ring have two it is common
The phenyl of carbon atom；X is halogen；The feed postition of the N- heterocycle carbines is：Alkali and N- heterocycle carbine thiazole salts are added, anti-
Answer and locally produce in system N- heterocycle carbines, the alkali is the mixture of DBU and potassium carbonate；
Step B：Seven yuan of lactones of biaryl are extracted from the crude product；That is compound 2.
2. microwave according to claim 1 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that reaction temperature
It is 50-80 DEG C.
3. microwave according to claim 1 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that potassium carbonate and
The mol ratio of N- heterocycle carbine thiazole salts is：1.8-2：1.
4. microwave according to claim 1 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that per 1mmol
20-25 μ L DBU are added in potassium carbonate.
5. microwave according to claim 1 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that the N- is miscellaneous
Ring Cabbeen is 3,4,5- trimethylthiazoles.
6. microwave according to claim 1 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that the N- is miscellaneous
Ring Cabbeen is with the compound 1 for equimolar is added.
7. microwave according to claim 1 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that the extraction
Method be：It is 1 with volume ratio:The ethyl acetate/petroleum ether of 35-40 is mobile phase, carries out column chromatography.
8. microwave according to claim 7 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that in the post
Before chromatography, first filter, concentrate.
9. microwave according to claim 1 quickly prepares seven yuan of methods of lactone of biaryl, it is characterised in that the polarity
Reversion reaction is carried out in Microwave-assisted synthesis/extractive reaction instrument.
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| CN103772343A (en) * | 2014-01-07 | 2014-05-07 | 浙江医学高等专科学校 | Preparation method of polyaryl seven-membered lactone |
| CN103772314A (en) * | 2014-01-07 | 2014-05-07 | 浙江医学高等专科学校 | Preparation method of carbene dipolymer |
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| CN103772343A (en) * | 2014-01-07 | 2014-05-07 | 浙江医学高等专科学校 | Preparation method of polyaryl seven-membered lactone |
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