CN105016998A - Synthesis method of aryldione compound - Google Patents
Synthesis method of aryldione compound Download PDFInfo
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- CN105016998A CN105016998A CN201510429932.2A CN201510429932A CN105016998A CN 105016998 A CN105016998 A CN 105016998A CN 201510429932 A CN201510429932 A CN 201510429932A CN 105016998 A CN105016998 A CN 105016998A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 55
- 238000001308 synthesis method Methods 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 238000010189 synthetic method Methods 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 239000010948 rhodium Substances 0.000 claims description 18
- 239000012752 auxiliary agent Substances 0.000 claims description 16
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 15
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 15
- JNGRYGYMVRKYBE-UHFFFAOYSA-N copper;2,2,2-trifluoroacetic acid Chemical compound [Cu].OC(=O)C(F)(F)F JNGRYGYMVRKYBE-UHFFFAOYSA-N 0.000 claims description 13
- -1 (1,5-cyclooctadiene) Tetrafluoroboric acid rhodium Chemical compound 0.000 claims description 12
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 241000545067 Venus Species 0.000 claims description 4
- QNZRVYCYEMYQMD-UHFFFAOYSA-N copper;pentane-2,4-dione Chemical compound [Cu].CC(=O)CC(C)=O QNZRVYCYEMYQMD-UHFFFAOYSA-N 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- FWBOFUGDKHMVPI-UHFFFAOYSA-K dicopper;2-oxidopropane-1,2,3-tricarboxylate Chemical compound [Cu+2].[Cu+2].[O-]C(=O)CC([O-])(C([O-])=O)CC([O-])=O FWBOFUGDKHMVPI-UHFFFAOYSA-K 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 239000004160 Ammonium persulphate Substances 0.000 claims description 3
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 3
- 235000019395 ammonium persulphate Nutrition 0.000 claims description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 3
- LYXVJDLJDXAJNW-UHFFFAOYSA-N cycloocta-1,5-diene;rhodium;trifluoromethanesulfonic acid Chemical compound [Rh].C1CC=CCCC=C1.OS(=O)(=O)C(F)(F)F LYXVJDLJDXAJNW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- MBHINSULENHCMF-UHFFFAOYSA-N n,n-dimethylpropanamide Chemical compound CCC(=O)N(C)C MBHINSULENHCMF-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 239000003054 catalyst Substances 0.000 abstract description 3
- 239000007800 oxidant agent Substances 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 150000005624 indolones Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003284 rhodium compounds Chemical class 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthesis method of an aryldione compound shown in the formula (III). The synthesis method comprises that a compound shown in the formula (I) and a compound shown in the formula (II) undergo a reaction in an organic solvent in the presence of a catalyst, an oxidizing agent and an assistant to produce the compound shown in the formula (III). In the formula, R1 and R2 respectively represent H, C1-C6 alkyl or halogen. Through reasonable selection and combination of the catalyst, the oxidizing agent, the assistant and the organic solvent, a product yield is high. The synthesis method is novel method for synthesis of the aryldione compound and has a good industrial application value and a good industrial production potential.
Description
Technical field
The present invention relates to a kind of synthetic method of ketone compounds, relate more particularly to a kind of synthetic method of aryl cyclohexadione compounds, belong to organic intermediate synthesis field.
Background technology
In organic chemical synthesis field, aryl cyclohexadione compounds has the structural unit of bioactive heterocycle as compounds such as imidazoles, quinoxaline, indolones for building.In addition, cyclohexadione compounds also Chang Zuowei synthesizes the precursor compound of N-heterocycle carbine, its for organometallics and field of catalytic chemistry very important.
Just because of so important advantage and the purposes of cyclohexadione compounds, therefore, the novel method for synthesizing developing cyclohexadione compounds has attracted the unremitting effort for it of numerous science researcher.
Up to now, in prior art, report the synthesis technique of multiple cyclohexadione compounds, such as:
Chen Shulin etc. (" Ruthenium-Catalyzed Oxidation of Alkenes atRoom Temperature:A Practical and Concise Approach to r-Diketones ", Organic Letters, 2011,13 (9), alkene 2274-2277) reporting a kind of ruthenium catalysis prepares through oxidizing reaction the novel method that α-diketone carrys out compound, it has good functional group tolerance, and reaction formula is as follows:
Su Yijin etc. (" Catalyst-Controlled Highly Selective Coupling andOxygenation of Olefins:A Direct Approach to Alcohols; Ketones; andDiketones ", Angew.Chem.Int.Ed., 2013,52,9808-9812) disclose a kind of 1, the synthetic method of 2-cyclohexadione compounds, its reaction formula is as follows:
As mentioned above, although disclose the synthetic method of some cyclohexadione compounds in prior art, however these methods more or less there is many defects, such as, need to prepare lead compound, reaction yield undesirable, relate to harsh reaction conditions etc.
In view of this, the present inventor is intended to by developing the summary of existing document and reagent, and a kind of novel method for synthesizing of aryl cyclohexadione compounds is provided, the method is by adopting choose reasonable and the combination of catalyzer, oxygenant, auxiliary agent and organic solvent, thus high yield can obtain object product, for the synthesis of this compounds provides completely new approach, industrially there are good using value and production potential.
Summary of the invention
In order to overcome above-mentioned pointed many defects, present inventor has performed deep research and exploration, after having paid enough creative works, thus completing the present invention.
Specifically, technical scheme of the present invention and content relate to the synthetic method of aryl cyclohexadione compounds shown in a kind of following formula (III),
Described method comprises: in organic solvent, and under catalyzer, oxygenant and auxiliary agent exist, following formula (I) compound and following formula (II) compound react, thus obtain described formula (III) compound,
Wherein, R
1, R
2be selected from H, C independently of one another
1-C
6alkyl or halogen.
In described synthetic method of the present invention, described C
1-C
6the implication of alkyl refers to the straight or branched alkyl with 1-6 carbon atom, such as can be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl or n-hexyl etc. in non-limiting manner.
In described synthetic method of the present invention, the implication of described halogen refers to haloid element, non-exclusively such as can be F, Cl, Br or I.
In described synthetic method of the present invention, described catalyzer is selected from Rh (COD)
2bF
4(two (1,5-cyclooctadiene) Tetrafluoroboric acid rhodium), Rh (NBD)
2bF
4(two (norbornadiene) Tetrafluoroboric acid rhodium), Rh (COD)
2sO
3cF
3any one in (two (1,5-cyclooctadiene) trifluoromethanesulfonic acid rhodium), most preferably is Rh (COD)
2sO
3cF
3.
In described synthetic method of the present invention, described oxygenant is any one in metachloroperbenzoic acid, tertbutyl peroxide, hydrogen peroxide, t-butyl per(oxy)benzoate, DDQ (DDQ), ammonium persulphate or ceric ammonium nitrate etc., most preferably is metachloroperbenzoic acid.
In described synthetic method of the present invention, described auxiliary agent is any one in venus crystals, trifluoroacetic acid copper, acetylacetone copper or Cuprocitrol, most preferably is trifluoroacetic acid copper.
In described synthetic method of the present invention, described organic solvent is the mixture of N, N-dialkyl amide compounds and ethanol, and the volume ratio of described N, N-dialkyl amide compounds and ethanol is 1:4.
Wherein, described N, N-dialkyl amide compounds is any one in DMF, N,N-dimethylacetamide or N, N-dimethylpropionamide, most preferably is N,N-dimethylacetamide.
The consumption of described organic solvent is not particularly limited, and can select according to the common practise in organic synthesis field, such as, select to make to react the amount steadily can carrying out, be easy to control, or is convenient to the amount etc. of aftertreatment.
In described synthetic method of the present invention, the mol ratio of described formula (I) compound and formula (II) compound is 1:1.2-1.8, such as, can be 1:1.2,1:1.4,1:1.6 or 1:1.8.
In described synthetic method of the present invention, the mol ratio of described formula (I) compound and catalyzer is 1:0.03-0.06, such as can be 1:0.03,1:0.04,1:0.05 or 1:0.06 in non-limiting manner.
In described synthetic method of the present invention, the mol ratio of described formula (I) compound and oxygenant is 1:2-3, such as can be 1:2,1:2.5 or 1:3 in non-limiting manner.
In described synthetic method of the present invention, the mol ratio of described formula (I) compound and auxiliary agent is 1:0.1-0.2, such as can be 1:0.1,1:0.15 or 1:0.2 in non-limiting manner
In described synthetic method of the present invention, temperature of reaction is 40-60 DEG C, such as, can be 40 DEG C, 50 DEG C or 60 DEG C.
In described synthetic method of the present invention, the reaction times is 3-6 hour, such as, can be 3 hours, 4 hours, 5 hours or 6 hours.
In described synthetic method of the present invention, aftertreatment after reaction terminates is as follows: after reaction terminates, naturally cool to room temperature, filters, filtrate is fully washed with deionized water, then be extracted with ethyl acetate 2-3 time, merge organic phase, and with anhydrous magnesium sulfate drying, concentrating under reduced pressure, residue is crossed silica gel column chromatography and is separated, and take volume ratio as the normal hexane of 1:2 and the mixed solution of ethyl acetate is eluting solvent, thus obtains described formula (III) compound.
Comprehensively above-mentioned, present inventors have proposed a kind of synthetic method of aryl cyclohexadione compounds, the method is by adopting choose reasonable and the combination of catalyzer, oxygenant, auxiliary agent and organic solvent, thus high yield can obtain object product, for the synthesis of this compounds provides completely new approach, industrially there are good using value and production potential.
Embodiment
Below by specific embodiment, the present invention is described in detail; but the purposes of these exemplary embodiments and object are only used for exemplifying the present invention; not any type of any restriction is formed to real protection scope of the present invention, more non-protection scope of the present invention is confined to this.
Embodiment 1
Under room temperature, (be the N of volume ratio 1:4 to appropriate organic solvent, the mixture of N-N,N-DIMETHYLACETAMIDE and ethanol) in, add 100mmol above formula (I) compound, 120mmol above formula (II) compound, 3mmol catalyzer Rh (COD)
2sO
3cF
3, 200mmol oxygenant metachloroperbenzoic acid and 10mmol auxiliary agent trifluoroacetic acid copper, then stir and be warming up to 40 DEG C, and stirring reaction 6 hours at such a temperature.
After reaction terminates, naturally cool to room temperature, filter, filtrate is fully washed with deionized water, then be extracted with ethyl acetate 2-3 time, merge organic phase, and with anhydrous magnesium sulfate drying, concentrating under reduced pressure, residue is crossed silica gel column chromatography and is separated, take volume ratio as the normal hexane of 1:2 and the mixed solution of ethyl acetate be eluting solvent, thus obtain above formula (III) compound, productive rate is 97.5%.
1H NMR(CDCl
3,400MHz):δ7.98(d,J＝8.0Hz,2H),7.86(d,J＝8.0Hz,2H),7.64(t,J＝8.0Hz,1H),7.51(t,J＝8.0Hz,2H),7.32(d,J＝8.0Hz,2H),2.46(s,3H)。
HRMS(ESI)([M+H]
+):224。
Embodiment 2
Under room temperature, (be the N of volume ratio 1:4 to appropriate organic solvent, the mixture of N-N,N-DIMETHYLACETAMIDE and ethanol) in, add 100mmol above formula (I) compound, 150mmol above formula (II) compound, 5mmol catalyzer Rh (COD)
2sO
3cF
3, 250mmol oxygenant metachloroperbenzoic acid and 15mmol auxiliary agent trifluoroacetic acid copper, then stir and be warming up to 50 DEG C, and stirring reaction 5 hours at such a temperature.
After reaction terminates, naturally cool to room temperature, filter, filtrate is fully washed with deionized water, then be extracted with ethyl acetate 2-3 time, merge organic phase, and with anhydrous magnesium sulfate drying, concentrating under reduced pressure, residue is crossed silica gel column chromatography and is separated, take volume ratio as the normal hexane of 1:2 and the mixed solution of ethyl acetate be eluting solvent, thus obtain above formula (III) compound (wherein t-Bu is the tertiary butyl), productive rate is 97.2%.
1H NMR(CDCl
3,400MHz):δ7.97(d,J＝8.0Hz,2H),7.90(d,J＝8.0Hz,2H),7.65(t,J＝8.0Hz,1H),7.54-7.47(m,4H),1.34(s,9H)。
HRMS(ESI)([M+H]
+):266。
Embodiment 3
Under room temperature, (be the N of volume ratio 1:4 to appropriate organic solvent, the mixture of N-N,N-DIMETHYLACETAMIDE and ethanol) in, add 100mmol above formula (I) compound, 180mmol above formula (II) compound, 4mmol catalyzer Rh (COD)
2sO
3cF
3, 300mmol oxygenant metachloroperbenzoic acid and 20mmol auxiliary agent trifluoroacetic acid copper, then stir and be warming up to 60 DEG C, and stirring reaction 3 hours at such a temperature.
After reaction terminates, naturally cool to room temperature, filter, filtrate is fully washed with deionized water, then be extracted with ethyl acetate 2-3 time, merge organic phase, and with anhydrous magnesium sulfate drying, concentrating under reduced pressure, residue is crossed silica gel column chromatography and is separated, take volume ratio as the normal hexane of 1:2 and the mixed solution of ethyl acetate be eluting solvent, thus obtain above formula (III) compound, productive rate is 97.1%.
1H NMR(CDCl
3,400MHz):δ7.99-7.91(m,4H),7.65(t,J＝8.0Hz,1H),7.55-7.47(m,4H)。
HRMS(ESI)([M+H]
+):244。
Embodiment 4
Under room temperature, (be the N of volume ratio 1:4 to appropriate organic solvent, the mixture of N-N,N-DIMETHYLACETAMIDE and ethanol) in, add 100mmol above formula (I) compound, 140mmol above formula (II) compound, 6mmol catalyzer Rh (COD)
2sO
3cF
3, 220mmol oxygenant metachloroperbenzoic acid and 12mmol auxiliary agent trifluoroacetic acid copper, then stir and be warming up to 45 DEG C, and stirring reaction 4 hours at such a temperature.
After reaction terminates, naturally cool to room temperature, filter, filtrate is fully washed with deionized water, then be extracted with ethyl acetate 2-3 time, merge organic phase, and with anhydrous magnesium sulfate drying, concentrating under reduced pressure, residue is crossed silica gel column chromatography and is separated, take volume ratio as the normal hexane of 1:2 and the mixed solution of ethyl acetate be eluting solvent, thus obtain above formula (III) compound, productive rate is 97.7%.
1H NMR(CDCl
3,400MHz):δ7.98(d,J＝8.0Hz,2H),7.84(d,J＝8.0Hz,2H),7.67(d,J＝8.0Hz,3H),7.53(t,J＝8.0Hz,2H)。
HRMS(ESI)([M+H]
+):290。
Embodiment 5-12
Embodiment 5-8: remove catalyzer wherein by Rh (COD)
2sO
3cF
3replace with Rh (COD)
2bF
4outward, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 5-8 in turn.
Embodiment 9-12: remove catalyzer wherein by Rh (COD)
2sO
3cF
3replace with Rh (NBD)
2bF
4outward, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 9-12 in turn.
The results are shown in following table 1.
Table 1
As can be seen here, in rhodium catalyst, Rh (COD)
2sO
3cF
3there is best catalytic effect, and the catalytic capability of other rhodium compound all there is remarkable reduction, reduce about 10 percentage points.
Embodiment 13-36
Embodiment 13-16: except replacing with except tertbutyl peroxide by metachloroperbenzoic acid wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 13-16 in turn.
Embodiment 17-20: except replacing with except hydrogen peroxide by metachloroperbenzoic acid wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 17-20 in turn.
Embodiment 21-24: except replacing with except t-butyl per(oxy)benzoate by metachloroperbenzoic acid wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 21-24 in turn.
Embodiment 25-28: remove metachloroperbenzoic acid wherein
2replace with outside DDQ, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 25-28 in turn.
Embodiment 29-32: except replacing with except ammonium persulphate by metachloroperbenzoic acid wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 29-32 in turn.
Embodiment 33-36: except replacing with except ceric ammonium nitrate by metachloroperbenzoic acid wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 33-36 in turn.
The results are shown in following table 2.
Table 2
As can be seen here, the kind of oxygenant has a strong impact on this final products collection efficiency, and wherein metachloroperbenzoic acid has best oxidation effectiveness, and other oxygenant all causes productive rate to have significantly or even significantly reduces.
Embodiment 37-52
Embodiment 37-40: except replacing with except venus crystals by trifluoroacetic acid copper wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 37-40 in turn.
Embodiment 41-44: except replacing with except acetylacetone copper by trifluoroacetic acid copper wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 41-44 in turn.
Embodiment 45-48: except replacing to except Cuprocitrol by trifluoroacetic acid copper wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 45-48 in turn.
Embodiment 49-52: except dispensing auxiliary agent, i.e. inapplicable trifluoroacetic acid copper, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 49-52 in turn.
The results are shown in following table 3.
Table 3
As can be seen here: 1, when not making used additives, products collection efficiency has significant reduction, and this proves that the existence of auxiliary agent can improve product, achieves the function of proof promoting reaction.2, in all auxiliary agents, trifluoroacetic acid copper has best facilitation effect, even if the venus crystals very similar with it, its products collection efficiency also has obvious reduction, and the reduction of acetylacetone copper and Cuprocitrol is then more obvious.
Embodiment 53-68
Embodiment 53-56: except replacing with except DMF by N,N-dimethylacetamide wherein, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 53-56 in turn.
Embodiment 57-60: except N,N-dimethylacetamide is wherein replaced with N, outside N-dimethylpropionamide, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 57-60 in turn.
Embodiment 61-64: except only using N,N-dimethylacetamide as except single solvent, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 61-64 in turn.
Embodiment 65-68: except only using ethanol as except single solvent, other operation is all identical, thus is repeated embodiment 1-4, obtains embodiment 65-68 in turn.
Experimental result is as shown in table 4 below.
Table 4
The result display of table 4, in all amidess, N,N-dimethylacetamide has best solvent effect; Also can finding out, when being used alone N,N-dimethylacetamide or ethanol as single solvent, products collection efficiency all will be caused to decrease, especially only use reduce during ethanol the most remarkable.This demonstrate that the mixed solvent only having and adopt N,N-dimethylacetamide and ethanol simultaneously, just can obtain excellent technique effect of the present invention.
Comprehensively above-mentioned, the present invention creatively proposes a kind of synthetic method of aryl cyclohexadione compounds, the method is by adopting choose reasonable and the combination of catalyzer, oxygenant, auxiliary agent and organic solvent, thus high yield can obtain object product, for the synthesis of this compounds provides completely new approach, industrially there are good using value and production potential.
Should be appreciated that the purposes of these embodiments is only not intended to for illustration of the present invention limit the scope of the invention.In addition; also should understand; after having read technology contents of the present invention, those skilled in the art can make various change, amendment and/or modification to the present invention, and these all equivalent form of values fall within the protection domain that the application's appended claims limits equally.
Claims (10)
1. a synthetic method for aryl cyclohexadione compounds shown in following formula (III),
Described method comprises: in organic solvent, and under catalyzer, oxygenant and auxiliary agent exist, following formula (I) compound and following formula (II) compound react, thus obtain described formula (III) compound,
Wherein, R
1, R
2be selected from H, C independently of one another
1-C
6alkyl or halogen.
2. synthetic method as claimed in claim 1, is characterized in that: described catalyzer is selected from Rh (COD)
2bF
4(two (1,5-cyclooctadiene) Tetrafluoroboric acid rhodium), Rh (NBD)
2bF
4(two (norbornadiene) Tetrafluoroboric acid rhodium), Rh (COD)
2sO
3cF
3any one in (two (1,5-cyclooctadiene) trifluoromethanesulfonic acid rhodium), most preferably is Rh (COD)
2sO
3cF
3.
3. synthetic method as claimed in claim 1 or 2, it is characterized in that: described oxygenant is any one in metachloroperbenzoic acid, tertbutyl peroxide, hydrogen peroxide, t-butyl per(oxy)benzoate, DDQ (DDQ), ammonium persulphate or ceric ammonium nitrate etc., most preferably is metachloroperbenzoic acid.
4. the synthetic method as described in any one of claim 1-3, is characterized in that: described auxiliary agent is any one in venus crystals, trifluoroacetic acid copper, acetylacetone copper or Cuprocitrol, most preferably is trifluoroacetic acid copper.
5. the synthetic method as described in any one of claim 1-4, is characterized in that: described organic solvent is the mixture of N, N-dialkyl amide compounds and ethanol, and the volume ratio of described N, N-dialkyl amide compounds and ethanol is 1:4;
Wherein, described N, N-dialkyl amide compounds is any one in DMF, N,N-dimethylacetamide or N, N-dimethylpropionamide, most preferably is N,N-dimethylacetamide.
6. the synthetic method as described in any one of claim 1-5, is characterized in that: the mol ratio of described formula (I) compound and formula (II) compound is 1:1.2-1.8.
7. the synthetic method as described in any one of claim 1-6, is characterized in that: the mol ratio of described formula (I) compound and catalyzer is 1:0.03-0.06.
8. the synthetic method as described in any one of claim 1-7, is characterized in that: the mol ratio of described formula (I) compound and oxygenant is 1:2-3.
9. the synthetic method as described in any one of claim 1-8, is characterized in that: the mol ratio of described formula (I) compound and auxiliary agent is 1:0.1-0.2.
10. the synthetic method as described in any one of claim 1-9, is characterized in that: temperature of reaction is 40-60 DEG C; Reaction times is 3-6 hour.
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| CN102070383A (en) * | 2011-01-27 | 2011-05-25 | 苏州大学 | Method for preparing 1,2-diketone by performing catalytic oxidation on olefin |
| CN103274917A (en) * | 2013-06-17 | 2013-09-04 | 浙江工业大学 | Method for catalyzing and synthesizing benzil derivatives from alkali type copper fluoride |
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| CN102070383A (en) * | 2011-01-27 | 2011-05-25 | 苏州大学 | Method for preparing 1,2-diketone by performing catalytic oxidation on olefin |
| CN103274917A (en) * | 2013-06-17 | 2013-09-04 | 浙江工业大学 | Method for catalyzing and synthesizing benzil derivatives from alkali type copper fluoride |
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| CN105294600B (en) * | 2015-11-29 | 2017-11-07 | 重庆天春科技有限公司 | A kind of synthetic method of medicine intermediate diketone aminated compounds |
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