CN103880699B - Method for synthesizing imides compounds - Google Patents
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- CN103880699B CN103880699B CN201410142432.6A CN201410142432A CN103880699B CN 103880699 B CN103880699 B CN 103880699B CN 201410142432 A CN201410142432 A CN 201410142432A CN 103880699 B CN103880699 B CN 103880699B
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- 238000000034 method Methods 0.000 title claims abstract description 12
- -1 imides compounds Chemical class 0.000 title abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- 238000010189 synthetic method Methods 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 239000012752 auxiliary agent Substances 0.000 claims description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 11
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- 229960001866 silicon dioxide Drugs 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 239000003054 catalyst Substances 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 238000002360 preparation method Methods 0.000 abstract description 6
- 238000002474 experimental method Methods 0.000 abstract description 3
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 229910021577 Iron(II) chloride Inorganic materials 0.000 abstract 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 abstract 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 7
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 238000006555 catalytic reaction Methods 0.000 description 5
- 150000003949 imides Chemical class 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 3
- 238000005576 amination reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229940059260 amidate Drugs 0.000 description 2
- 230000009435 amidation Effects 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- UXKCLTPQRBKROC-UHFFFAOYSA-N C(C)(C)C1=C(C(=CC(=C1)C(C)C)C(C)C)C1=CC=CC=C1.[P] Chemical group C(C)(C)C1=C(C(=CC(=C1)C(C)C)C(C)C)C1=CC=CC=C1.[P] UXKCLTPQRBKROC-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000032825 Ring chromosome 2 syndrome Diseases 0.000 description 1
- ZYPGADGCNXOUJP-CXVPHVKISA-N Variotin Chemical compound CCCC[C@@H](O)\C=C(/C)\C=C\C=C\C(=O)N1CCCC1=O ZYPGADGCNXOUJP-CXVPHVKISA-N 0.000 description 1
- XSWALQKVYPLUJA-UHFFFAOYSA-N [Ru].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical compound [Ru].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 XSWALQKVYPLUJA-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 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
- 238000013461 design Methods 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- ZYPGADGCNXOUJP-UHFFFAOYSA-N dl-Variotin Natural products CCCCC(O)C=C(C)C=CC=CC(=O)N1CCCC1=O ZYPGADGCNXOUJP-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 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
- 239000011737 fluorine Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical class Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 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
- 238000012423 maintenance Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 229930014626 natural product Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 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
- 150000003334 secondary amides Chemical class 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a method for synthesizing imides compounds. According to the method disclosed by the invention, efficient synthesis of imides compounds is promoted by a catalyst system with FeCl2 as an aid, and an optimal combination of components is optimized by means of a single factor experiment to obtain an optimal complex catalytic system; the preparation process has developed a method for preparing the imides compounds, ensures high reaction yield and has broad prospects for large-scale applications and potential market value.
Description
Technical field
The present invention relates to a kind of synthetic method of imide analog compounds, relate more specifically to a kind of FeCl
2the synthetic method of imide analog compounds is prepared in the catalysis of/auxiliary agent, belongs to organic medicinal synthesis field.
Background technology
At present, acid imide structure is extensively present in and manyly has among bioactive drug molecule, and in the pharmaceutical synthesis field of reality, is subject to extensive concern, such as, and Variotin, Anixidan and many synthesis comprising heterogeneous ring compound natural product.
As everyone knows, acyl chlorides is comparatively traditional synthesis strategy as acylating reagent for constructing imide compound, but the acyl chlorides reagent involved by this kind of method has many shortcoming such as unstable, corrodibility.In addition, by the direct oxidation coupling between c h bond and N-H key be used for the structure of C-N key be also prior art the method commonly used, the NH nucleophilic reagent that it mainly adopts has aminated compounds or specific acid amides (as picolinamide or primary amide etc.), and example is as follows:
Liang Chungen etc. (" Efficient Diastereoselective IntermolecularRhodium-Catalyzed C-H Amination ", Angew.Chem.Int.Ed., 2006,45,4641-4644) report a kind of C-H amination reaction of rhodium catalysis, its adopt sulfimide amide compound be nitrene precursor and containing c h bond substrate as restriction component, for C-H amination reaction in the molecule of rhodium catalysis, reaction formula is as follows:
Philip Wai Hong Chan etc. (" Highly Efficient Ruthenium (II) Phorphyrin Catalyzed Amidation of Aldehydes ", Angew.Chem.Int.Ed., 2008,47,1138-1140) reporting a kind of is nitrogenous source with PhI=NTs, under the catalysis of ruthenium-porphyrin complex, realize the amidate action of C-H, its reaction formula is as follows:
(" the Synthesis of Imides by Palladium-Catalyzed C-H such as Bian Yong-Jun
Functionalization of Aldehydes with Secondary Amides "; Chem.Eur.J.2013; 19; 1129-1133) to report the N-aromatic ring-2-methane amide that a kind of aldehyde compound and N-replace be raw material; the method for synthesizing secondary imide compound under palladium catalyst effect, its reaction formula is as follows:
Wang Long etc. (" Highly Efficient Copper-Catalyzed Amidation ofAldehydes by C-H Activation ", Chem.Eur.J.2008,14,10722-10726) disclose a kind of amidate action of aldehyde compound of copper catalysis under NBS exists, the method is simple, practical and economy is strong, and its reaction formula is as follows:
But above-mentioned prior art still can not meet current medical intermediate, the synthesis of chemical intermediate and research and development, its mainly due to: 1, the product yield of prior art is still not high enough; 2, catalyzer relates generally to expensive precious metal or complex compound, significantly increases production cost.The defect that the present inventor exists for prior art, is intended to be explored by Design Theory and experimental study a kind of novel preparation process of practical, imide compound that reaction yield is high, thus fully meets the Production requirement in the fields such as chemical and medicine industry.
Summary of the invention
In order to overcome above-mentioned pointed many defects, the present inventor, to this has been further investigation, after having paid a large amount of creative work, thus develops a kind of novel preparation process of imide compound, and then completes the present invention.
Specifically, technical scheme of the present invention and content relate to the synthetic method of a kind of formula (III) compound, and described method comprises the steps: in reactor, add formula (I) compound and FeCl
2, stir and pass into nitrogen maintenance nitrogen atmosphere, then in system, adding solvent toluene, under stirring, add formula (II) compound, TBHP (tertbutyl peroxide) and auxiliary agent again, continue logical
Seal after passing into nitrogen, temperature reaction, add that shrend is gone out, extracted with diethyl ether after completion of the reaction, merge after organic phase after anhydrous sodium sulfate drying, filtration, vacuum concentration, residue by silicagel column chromatogram purification, can obtain formula (III) compound:
Wherein:
R
1for with substituting group or unsubstituted C
1-C
6alkyl, with substituting group or unsubstituted phenyl;
R
2, R
3be with substituting group or unsubstituted C independently of one another
1-C
6alkyl, with substituting group or unsubstituted phenyl or benzyl;
R
1-R
3in described substituting group be C
1-C
6alkyl, C
1-C
6alkoxy or halogen.
In described synthetic method of the present invention, described halogen is fluorine, chlorine, bromine or iodine atom.
In described synthetic method of the present invention, described C
1-C
6alkyl refers to the alkyl with 1-6 carbon atom, and it can be straight or branched, such as can be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl, n-hexyl etc. in non-limiting manner.
In described synthetic method of the present invention, described C
1-C
6alkoxyl group refers to C
1-C
6the group that alkyl is connected with Sauerstoffatom.
In described synthetic method of the present invention, described auxiliary agent is 2-dicyclohexylphosphontetrafluoroborate-2', 4', 6'-tri isopropyl biphenyl (Xphos), 1,10-o-phenanthroline and I
2o
5mixture, wherein 2-dicyclohexyl phosphorus-2', 4', 6'-tri isopropyl biphenyl, 1,10-phenanthroline and I
2o
5mass ratio be 1:0.2-0.5:0.1-0.3, preferred 1:0.4:0.2.
In described synthetic method of the present invention, described formula (I) compound and FeCl
2mol ratio be 1:0.02-0.1, such as can be 1:0.02,1:0.03,1:0.04,1:0.05,1:0.06,1:0.07,1:0.08,1:0.09 or 1:0.1, be preferably 1:0.04-0.07.
In described synthetic method of the present invention, the mol ratio of described formula (I) compound and formula (II) compound is 1:2-5, can be 1:2,1:2.5,1:3,1:3.5,1:4,1:4.5 or 1:5 in non-limiting manner, is preferably 1:2.5-4.
In described synthetic method of the present invention, the mol ratio of described formula (I) compound and TBHP is 1:2-3, such as can be 1:2,1:2.1,1:2.2,1:2.3,1:2.4,1:2.5,1:2.6,1:2.7,1:2.8,1:2.9 or 1:3, be preferably 1:2.2-2.5.
In described synthetic method of the present invention, described formula (I) compound is 1:5-8mol/L with the molecular volume ratio of toluene, namely every 1mol formula (I) compound uses 5-8L toluene, can be 1:5mol/L, 1:5.5mol/L, 1:6mol/L, 1:6.5mol/L, 1:7mol/L, 1:7.5mol/L or 1:8mol/L in non-limiting manner, be preferably 1:5.5-6.5mol/L.
In described synthetic method of the present invention, in mole described formula (I) compound with in gram the ratio of auxiliary agent for 1:8-12mol/g, namely every 1mol formula (I) compound uses 8-12g auxiliary agent, can be 1:8mol/g, 1:9mol/g, 1:10mol/g, 1:11mol/g or 1:12mol/g in non-limiting manner.
In described synthetic method of the present invention, the reaction times is without particular limitation, such as, can be 10-14h, can be 10h, 11h, 12h, 13h or 14h in non-limiting manner.
In described synthetic method of the present invention, temperature of reaction is 45-55 DEG C, such as, can be 45 DEG C, 50 DEG C or 55 DEG C.
In described synthetic method of the present invention, described silica gel chromatography can use any silica gel column chromatography as known in the art, such as use 200-400 object silica gel, elutriant is the mixture of n-propyl alcohol and sherwood oil, and wherein the volume ratio of n-propyl alcohol, sherwood oil is 1:1.5.Unless otherwise prescribed, the silica gel chromatography operation below in all embodiments be use 200-400 object silica gel, elutriant to be the volume ratio n-propyl alcohol that is 1:1.5 and sherwood oil mixture to carry out purification process.
Compared with prior art, beneficial effect of the present invention is:
1, FeCl is adopted first
2the catalyst system of/auxiliary agent, achieves acid amides and aldehyde compound and reacts and prepare imide compound, and significantly improve reaction yield.
2, have studied the impact of this factor of adjuvant component kind, filtered out the best of breed of adjuvant component, effective synergistic catalyst improves reactivity worth.
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
1mol formula (I) compound and 0.06mol FeCl is added in reactor
2stir and pass into nitrogen and maintain nitrogen atmosphere, then in system, 6L solvent toluene is added, 2-dicyclohexylphosphontetrafluoroborate-the 2' that 3mol formula (II) compound, 2.2mol TBHP and mass ratio are 1:0.4:0.2 is added again under stirring, 4', 6'-tri isopropyl biphenyl (Xphos), 1,10-o-phenanthroline and I
2o
5agent mixture (total mass is 10g), seal after continuing all to enter nitrogen, heat up 50 DEG C of reaction 14h, add shrend after completion of the reaction to go out, adopt extracted with diethyl ether, after merging organic phase after anhydrous sodium sulfate drying, filtration, vacuum concentration, residue by silicagel column chromatogram purification, can obtain formula (III) compound, yield is 93.8%, and purity is 98.9% (HPLC).
1H NMR(400MHz,CDCl
3)δ=7.62-7.49(m,5H),3.21(s,3H),2.33(s,3H)；
MS[M+H]
+:177.07。
Embodiment 2
1mol formula (I) compound and 0.04mol FeCl is added in reactor
2stir and pass into nitrogen and maintain nitrogen atmosphere, then in system, 5.5L solvent toluene is added, 2-dicyclohexylphosphontetrafluoroborate-the 2' that 2.5mol formula (II) compound, 2.5mol TBHP and mass ratio are 1:0.4:0.2 is added again under stirring, 4', 6'-tri isopropyl biphenyl (Xphos), 1,10-o-phenanthroline and I
2o
5agent mixture (total mass is 12g), seal after continuing all to enter nitrogen, heat up 55 DEG C of reaction 12h, add shrend after completion of the reaction to go out, adopt extracted with diethyl ether, after merging organic phase after anhydrous sodium sulfate drying, filtration, vacuum concentration, residue by silicagel column chromatogram purification, can obtain formula (III) compound, yield is 94.6%, and purity is 98.7% (HPLC).
1H NMR(400MHz,CDCl
3)δ=7.61-7.59(m,2H),7.36-7.29(m,3H),7.07-7.04(m,2H),6.82(m,2H),3.71(s,3H),2.38(s,3H)；
MS[M+H]
+:269.10。
Embodiment 3
1mol formula (I) compound and 0.05molFeCl is added in reactor
2stir and pass into nitrogen and maintain nitrogen atmosphere, then in system, 6.5L solvent toluene is added, 2-dicyclohexylphosphontetrafluoroborate-the 2' that 4mol formula (II) compound, 2.4mol TBHP and mass ratio are 1:0.4:0.2 is added again under stirring, 4', 6'-tri isopropyl biphenyl (Xphos), 1,10-o-phenanthroline and I
2o
5agent mixture (total mass is 8g), seal after continuing all to enter nitrogen, heat up 50 DEG C of reaction 13h, add shrend after completion of the reaction to go out, adopt extracted with diethyl ether, after merging organic phase after anhydrous sodium sulfate drying, filtration, vacuum concentration, residue by silicagel column chromatogram purification, can obtain formula (III) compound, yield is 94.1%, and purity is 98.8% (HPLC).
1H NMR(400MHz,CDCl
3)δ=7.62(d,J=8.0Hz,2H),7.41-7.22(m,6H),7.16(d,J=8.0Hz,2H),2.44(s,3H)；
MS[M+H]
+:240.10。
Embodiment 4
1mol formula (I) compound and 0.07mol FeCl is added in reactor
2stir and pass into nitrogen and maintain nitrogen atmosphere, then in system, 6L solvent toluene is added, 2-dicyclohexylphosphontetrafluoroborate-the 2' that 3.5mol formula (II) compound, 2.3mol TBHP and mass ratio are 1:0.4:0.2 is added again under stirring, 4', 6'-tri isopropyl biphenyl (Xphos), 1,10-o-phenanthroline and I
2o
5agent mixture (total mass is 10g), seal after continuing all to enter nitrogen, heat up 55 DEG C of reaction 11h, add shrend after completion of the reaction to go out, adopt extracted with diethyl ether, after merging organic phase after anhydrous sodium sulfate drying, filtration, vacuum concentration, residue by silicagel column chromatogram purification, can obtain formula (III) compound, yield is 94.5%, and purity is 98.4% (HPLC).
1H NMR(400MHz,CDCl
3)δ=7.45-7.43(m,1H),7.38-7.36(m,1H),7.26-7.12(m,7H),4.95(s,2H),2.31(s,3H)；
MS[M+H]
+:271.10。
Embodiment 5-8
Remove FeCl
2replace with outside following component, implement embodiment 5-8 respectively in the mode identical with embodiment 1-4, the corresponding relation of component and experimental result is as shown in table 1 below.
Table 1
"--" expression is not added.
From the result of embodiment 1-4 and table 1, the present inventor studies discovery by experiment: the catalyzer that can produce optimum catalytic performance in this catalyzer/adjuvant system is FeCl
2, and show the low yield that differs greatly when other similar molysite compounds are catalyzer or do not react.Which demonstrating catalyst type is the important factor affecting reaction process, secondly also may there is obvious correlation between catalyzer and auxiliary agent.
Embodiment 9-12
Remove the 2-dicyclohexylphosphontetrafluoroborate-2' in auxiliary agent, 4', 6'-tri isopropyl biphenyl (Xphos) replaces with outside following component, implements embodiment 9-12 respectively in the mode identical with embodiment 1-4, and the corresponding relation of component and experimental result is as shown in table 2 below.
Table 2
Embodiment 13-16
Except being replaced with outside following component by 1,10-o-phenanthroline in auxiliary agent, implement embodiment 13-16 respectively in the mode identical with embodiment 1-4, the corresponding relation of component and experimental result is as shown in table 3 below.
Table 3
Embodiment 17-20
Except not adding I in auxiliary agent
2o
5, implement embodiment 17-20 respectively in the mode identical with embodiment 1-4 outward, the corresponding relation of component and experimental result is as shown in table 4 below.
Table 4
"--" expression is not added.
From the result of embodiment 1-4 and table 2-4, close association and synergy is there is between each component of auxiliary agent, by studying the kind of component 1 and component 2, optimized choice goes out 2-dicyclohexylphosphontetrafluoroborate-2', 4', 6'-tri isopropyl biphenyl (Xphos) and 1,10-o-phenanthroline, demonstrate component 3 by research component 3 indispensable in auxiliary agent, it can affect whole system reactivity worth.The method that the present inventor is combined with laboratory facilities by knowwhy, not only constructs the novel auxiliary system composite with iron salt catalyst, but also has carried out suitable selection to each component of auxiliary agent, achieves excellent technique effect simultaneously.
In sum, the present inventor is by a large amount of creative works, and have developed a kind of novel preparation process of imide compound, it is with FeCl
2the catalyst system of/auxiliary agent and achieve the efficient synthesis promoting imide compound, and be optimized by the best of breed of experiment of single factor means to component and obtain best catalyst system, this preparation technology has opened up the preparation method of imide compound, and has certain prospects for commercial application and market 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 (12)
1. a synthetic method for formula (III) compound, described method comprises the steps: in reactor, add formula (I) compound and FeCl
2stir and pass into nitrogen and maintain nitrogen atmosphere, then in system, solvent toluene is added, add formula (II) compound, TBHP and auxiliary agent under stirring again, seal after continuing to pass into nitrogen, temperature reaction, add that shrend is gone out, extracted with diethyl ether after completion of the reaction, after merging organic phase after anhydrous sodium sulfate drying, filtration, vacuum concentration, residue by silicagel column chromatogram purification, can obtain formula (III) compound:
Wherein:
R
1for with substituting group or unsubstituted C
1-C
6alkyl, with substituting group or unsubstituted phenyl;
R
2, R
3be with substituting group or unsubstituted C independently of one another
1-C
6alkyl, with substituting group or unsubstituted phenyl or benzyl;
R
1-R
3in described substituting group be C
1-C
6alkyl, C
1-C
6alkoxy or halogen;
Described auxiliary agent is 2-dicyclohexylphosphontetrafluoroborate-2', 4', 6'-tri isopropyl biphenyl, 1,10-o-phenanthroline and I
2o
5mixture, 2-dicyclohexylphosphontetrafluoroborate-2' in described auxiliary agent, 4', 6'-tri isopropyl biphenyl, 1,10-phenanthroline and I
2o
5mass ratio be 1:0.2-0.5:0.1-0.3.
2. synthetic method as claimed in claim 1, is characterized in that: 2-dicyclohexylphosphontetrafluoroborate-2' in described auxiliary agent, 4', 6'-tri isopropyl biphenyl, 1,10-phenanthroline and I
2o
5mass ratio be 1:0.4:0.2.
3. synthetic method as claimed in claim 1 or 2, is characterized in that: described formula (I) compound and FeCl
2mol ratio be 1:0.02-0.1.
4. synthetic method as claimed in claim 3, is characterized in that: described formula (I) compound and FeCl
2mol ratio be 1:0.04-0.07.
5. synthetic method as claimed in claim 1 or 2, is characterized in that: the mol ratio of described formula (I) compound and formula (II) compound is 1:2-5.
6. synthetic method as claimed in claim 5, is characterized in that: the mol ratio of described formula (I) compound and formula (II) compound is 1:2.5-4.
7. synthetic method as claimed in claim 1 or 2, is characterized in that: the mol ratio of described formula (I) compound and TBHP is 1:2-3.
8. synthetic method as claimed in claim 7, is characterized in that: the mol ratio of described formula (I) compound and TBHP is 1:2.2-2.5.
9. synthetic method as claimed in claim 1 or 2, is characterized in that: described formula (I) compound is 1:5-8mol/L with the molecular volume ratio of toluene.
10. synthetic method as claimed in claim 9, is characterized in that: described formula (I) compound is 1:5.5-6.5mol/L with the molecular volume ratio of toluene.
11. synthetic methods as claimed in claim 1 or 2, is characterized in that: in mole described formula (I) compound with in gram the ratio of auxiliary agent for 1:8-12mol/g.
12. synthetic methods as claimed in claim 1 or 2, is characterized in that: the reaction times is 10-14h; Temperature of reaction is 45-55 DEG C.
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