CN104098476B - A kind of synthetic method of building the aminated compounds of unit as medicine structure - Google Patents
A kind of synthetic method of building the aminated compounds of unit as medicine structure Download PDFInfo
- Publication number
- CN104098476B CN104098476B CN201410378364.3A CN201410378364A CN104098476B CN 104098476 B CN104098476 B CN 104098476B CN 201410378364 A CN201410378364 A CN 201410378364A CN 104098476 B CN104098476 B CN 104098476B
- Authority
- CN
- China
- Prior art keywords
- formula
- synthetic method
- nickel complex
- reaction
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 40
- 238000010189 synthetic method Methods 0.000 title claims abstract description 19
- 239000003814 drug Substances 0.000 title description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 76
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 67
- 229910052759 nickel Inorganic materials 0.000 claims abstract description 38
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 34
- 239000003446 ligand Substances 0.000 claims abstract description 33
- 239000003960 organic solvent Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 48
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 239000000047 product Substances 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- -1 nitrogenous compound Chemical class 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 239000007810 chemical reaction solvent Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 239000012046 mixed solvent Substances 0.000 description 8
- 238000010926 purge Methods 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 238000009834 vaporization Methods 0.000 description 8
- 230000008016 vaporization Effects 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 3
- 235000010338 boric acid Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 1
- 241000545067 Venus Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical group 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 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
- 230000000052 comparative effect Effects 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 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
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002816 nickel compounds Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 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
- 239000012265 solid product Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Abstract
The present invention relates to a kind of synthetic method of aminated compounds, described method is using specific nickel complex as catalyzer, and uses Phosphine ligands, makes aminocompound and organic borate react in organic solvent, and obtains object product.The method has good products collection efficiency, and aftertreatment is simple, is a kind of brand-new synthetic method very with research and industrial value.
Description
Technical field
The present invention relates to a kind of synthetic method of nitrogenous compound, particularly a kind of synthetic method that can be used as the aminated compounds of medicine structure block unit, belongs to medicine intermediate synthesis field.
Background technology
Aminated compounds is a kind of very important compound, can be used to many active substances such as synthetic drugs, dyestuff, agricultural chemicals, liquid crystalline cpd, Photoactive compounds, has important function and position in organic chemical synthesis field.
Up to now, be developed the synthesis of multiple aminated compounds, such as nitroreduction becomes amino, thus obtain corresponding amine compound, and as more complicated aminated compounds, be developed cross-coupling reaction, thus obtain all kinds of aromatic amine compounds.
In addition, researcher also have developed the synthetic method using boric acid, and such as, under venus crystals exists, aminocompound can be obtained by reacting corresponding novel arylamine compound by aryl boric acid.
In the synthetic method of all use aryl boric acids, all need to use various Cu compounds as catalyzer, and use various catalyst aids etc., and for the catalyzer outside Cu, have little research, and reactions steps is long mostly, thus causes productive rate too low.
Therefore, how to obtain aminated compounds with a simpler process, this is for organic chemical synthesis worker, is still a very interested problem.
Summary of the invention
In order to overcome shortcoming existing in prior art, the present inventor finds to use nickel catalyzator, cycliborate and specific Phosphine ligands, thus corresponding aminated compounds can be obtained by aminocompound to organic borate one step, and the purity of product and yield are very high, thus complete the present invention.
The present invention relates to a kind of synthetic method of aminated compounds.
More specifically, the present invention relates to the synthetic method of aminated compounds shown in a kind of formula (I);
Described method is specially: using nickel complex as catalyzer, and under Phosphine ligands exists and in organic solvent, formula (II) compound and (III) compound react and obtain amine chemical combination shown in formula (I)
thing;
Wherein R is selected from H, halogen, C
1-C
4alkyl, C
1-C
4alkoxyl group, halo C
1-C
4alkyl or halo C
1-C
4alkoxyl group;
Ar is aryl, and described aryl can with 1-5 substituting group, and described substituting group is selected from halogen, C independently of one another
1-C
4alkyl, C
1-C
4alkoxyl group, halo C
1-C
4alkyl or halo C
1-C
4alkoxyl group;
R
1be selected from H, halogen or C
1-C
4alkyl;
X is basic metal, such as Li, Na or K, is preferably K.
In the present invention, C
1-C
4the implication of alkyl refers to the straight or branched alkyl with 1-4 carbon atom, that includes C
1alkyl, C
2alkyl, C
3alkyl or C
4alkyl, such as can be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl etc. in non-limiting manner.
In the present invention, C
1-C
4alkoxyl group refers to " C defined above
1-C
4alkyl " be connected with O atom after group.
In the present invention, halo C
1-C
4the implication of alkyl refers to the " C defined above be optionally substituted by halogen
1-C
4alkyl ".
In the present invention, halo C
1-C
4the implication of alkoxyl group refers to the " C defined above be optionally substituted by halogen
1-C
4alkoxyl group ".
In the present invention, the implication of " halogen " refers to haloid element, non-exclusively such as can be F, Cl, Br or I.
In the present invention, in structural formula (III)
with
represent positive charge and negative charge respectively.
In the present invention, Ar is aryl, and described aryl can be C
6-12aryl, such as, can be phenyl or naphthyl; Described aryl can with 1-5 substituting group, such as can with 1,2,3,4 or 5 substituting groups.
In the present invention, described nickel complex has following structural formula:
In the present invention, described Phosphine ligands has following structural formula:
In the present invention, described organic solvent is selected from any one or multiple in dimethyl formamide (DMF), chloroform, ether, tetracol phenixin, tetrahydrofuran (THF) (THF), toluene, chlorobenzene, acetone, ethyl acetate etc., be preferably dimethyl formamide (DMF), chloroform, ether, tetracol phenixin, in tetrahydrofuran (THF) (THF) any one or multiple, most preferably be dimethyl formamide (DMF).
In the present invention, according to a mole meter, formula (II) and the 1:1-3 of (III) compound, be preferably 1:2.
In the present invention, according to a mole meter, the ratio of formula (II) compound and nickel complex as catalyst agent is 1:0.04-0.1, is preferably 1:0.06-0.08.
In the present invention, according to a mole meter, the ratio of described nickel complex as catalyst agent and Phosphine ligands is 1:2-3.
In the present invention, temperature of reaction is 70-110 DEG C, such as, can be 70 DEG C, 80 DEG C, 90 DEG C, 100 DEG C or 110 DEG C.
In the present invention, the reaction times is 8-14 hour, is generally 8-10 hour.
In the present invention, described reaction can be carried out under atmosphere of inert gases.
In the present invention, the aftertreatment after reaction terminates completes by chromatography over CC, and wherein elutriant is the mixture of ethyl acetate and acetone, and both volumes are 1:1-3, is preferably 1:2.
As mentioned above, the present invention using nickel complex as catalyzer, under specific Phosphine ligands exists, can one step obtains object product by aminocompound and organic cyclic boronate salt, be a kind of brand-new synthetic method, there is good scientific research value.
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.
It should be noted that in all embodiments below and comparative example, unless otherwise indicated, otherwise the catalyzer used and part are nickel complex and Phosphine ligands that above-mentioned " summary of the invention " part gives concrete structure formula.
Embodiment 1
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 1 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:1, formula (II) is 1:0.04, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:2; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 14 hours at 70 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:1, collect elutriant, reduction vaporization removing elutriant, obtains object solid product.
Embodiment 2
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 2 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:2, formula (II) is 1:0.07, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:3; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 10 hours at 90 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:2, collect elutriant, reduction vaporization removing elutriant, obtains object product.
Embodiment 3
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 3 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:3, formula (II) is 1:0.1, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:2; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 8 hours at 110 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:3, collect elutriant, reduction vaporization removing elutriant, obtains object product.
Embodiment 4
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 4 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:1.5, formula (II) is 1:0.1, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:2.5; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 9 hours at 100 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:1, collect elutriant, reduction vaporization removing elutriant, obtains object product.
Embodiment 5
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 5 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:2.5, formula (II) is 1:0.05, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:3; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 11 hours at 90 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:2, collect elutriant, reduction vaporization removing elutriant, obtains object product.
Embodiment 6
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 6 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:2, formula (II) is 1:0.08, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:2; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 12 hours at 100 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:3, collect elutriant, reduction vaporization removing elutriant, obtains object product.
Embodiment 7
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 7 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:1, formula (II) is 1:0.1, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:3; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 14 hours at 80 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:1, collect elutriant, reduction vaporization removing elutriant, obtains object product.
Embodiment 8
In reaction vessel, add appropriate but be enough to, for the organic solvent DMF needed for reaction, then add the formula (II) in table 1 corresponding to embodiment 8 and formula (III) compound, then add nickel complex and Phosphine ligands; The mol ratio that the mol ratio of its Chinese style (II) and formula (III) compound is 1:3, formula (II) is 1:0.04, nickel complex and Phosphine ligands with the mol ratio of nickel complex is 1:2; Nitrogen purging is thorough, then continues nitrogen and fills, replaces 2-3 time, be divided into, heat and react 14 hours at 70 DEG C until be entirely nitrogen in reaction vessel.After reaction reaches the time, filtered while hot, then Rotary Evaporators is used to remove reaction solvent from filtrate, gained residue silica gel column chromatography is separated, ethyl acetate and the acetone mixed solvent of elutriant to be volume ratio be 1:2, collect elutriant, reduction vaporization removing elutriant, obtains object product.
Table 1. differential responses thing and product and productive rate
The nuclear magnetic resonance data of above-described embodiment products therefrom is as follows respectively:
Embodiment 1:
1h NMR (CDCl
3, 500 MHz): δ 7.19-7.23 (m, 4H), 7.01-7.03 (m, 4H), 6.91 (m, 2H), 5.63 (s, 1H);
13c NMR (CDCl
3, 125MHz) and δ 142.1 (2C), 128.1 (4C), 121.2 (4C), 116.3 (2C).
Embodiment 2:
1h NMR (CDCl
3, 500 MHz): δ 7.27-7.21 (m, 2H), 7.19 (t, J=7.9 Hz, 1H), 7.11 (d, 2H), 6.94-6.84 (m, 3H), 6.74 (d, 1H), 5.71 (s, 1H), 2.34 (s, 3H);
13c NMR (CDCl
3, 125 MHz) and δ 143.6,143.3,139.5,129.1 (2C), 129.0,121.2,120.5 (2C), 118.1,117.2,114.2,22.3.
Embodiment 3:
1h NMR (CDCl
3, 500 MHz): δ 7.17-7.22 (m, 2H), 7.01-6.96 (m, 2H), 6.94-6.88 (m, 4H), 6.82-6.75 (m, 1H), 5.50 (s, 1H);
13c NMR (CDCl
3, 125 MHz) and δ 158.4,143.4,138.7,129.8 (2C), 121.2 (2C), 119.2 (2C), 116.2,115.1 (2C).
Embodiment 4:
1h NMR (CDCl
3, 500 MHz): δ 7.23-7.18 (m, 2H), 7.12 (t, 1H), 7.01 (d, 2H), 6.91-6.83 (m, 3H), 6.70 (d, 1H), 5.71 (s, 1H), 2.35 (s, 3H);
13c NMR (CDCl
3, 125 MHz) and δ 143.5,143.3,138.9,129.1 (2C), 128.3,121.5,120.1 (2C), 118.7,118.2,115.3,22.8.
Embodiment 5:
1h NMR (CDCl
3, 500 MHz): δ 7.20-7.24 (m, 2H), 7.11-7.16 (m, 2H), 7.01-7.09 (m, 2H), 6.93-6.82 (m, 3H), 5.51 (s, 1H);
13c NMR (CDCl
3, 125 MHz) and δ 143.7,142.2,129.6 (2C), 129.1 (2C), 125.1,120.7 (2C), 118.2 (2C), 117.5.
Embodiment 6:
1h NMR (CDCl
3, 500 MHz): δ 7.11-7.02 (m, 3H), 6.82-6.89 (m, 2H), 6.42-6.36 (m, 2H), 6.31-6.37 (m, 1H), 5.49 (s, 1H), 3.71 (s, 3H), 3.69 (s, 3H);
13c NMR (CDCl
3, 125 MHz) and δ 161.5,155.1,145.2,136.1,131.2,121.6 (2C), 114.2 (2C), 107.7,104.2,102.1,56.1,54.6.
Embodiment 7:
1h NMR (CDCl
3, 500 MHz): δ 7.01-7.09 (m, 2H), 6.81-6.92 (m, 6H), 5.45 (s, 1H), 3.90 (s, 3H);
13c NMR (CDCl
3, 125MHz) and δ 155.4 (d, 1C), 153.7,141.2136.7,120.5 (2C), 118.2 (2C), 114.9 (d, 2C), 114.3 (2C), 54.6.
Embodiment 8:
1h NMR (CDCl
3, 500 MHz): δ 7.22-7.16 (m, 2H), 7.10 (t, 1H), 7.01 (d, 2H), 6.91-6.82 (m, 3H), 6.76 (d, 1H), 5.74 (s, 1H), 2.34 (s, 3H);
13c NMR (CDCl
3, 125 MHz) and δ 142.6,142.4,138.8,128.9 (2C), 128.1,122.3,121.2 (2C), 118.7,117.3,114.1,22.4.
Embodiment 9-16
Except nickel complex as catalyst agent is wherein replaced with except following organo-nickel compounds, implement embodiment 9-16 respectively in the mode identical with embodiment 1-8, use the yield of organo-nickel compounds, embodiment corresponding relation and corresponding product as shown in table 2 below.
Table 2. organo-nickel compounds and corresponding relation and products collection efficiency
Can be found out by upper table 2, when using other nickel compound as catalyzer, products collection efficiency sharply reduces, and even cannot react.
Embodiment 17-24
Replace with respectively except following phosphine compound except by Phosphine ligands wherein, implement embodiment 17-24 respectively in the mode identical with embodiment 1-8, use the yield of Phosphine ligands, embodiment corresponding relation and corresponding product as shown in table 3 below.
Table 3. Phosphine ligands, corresponding embodiment and products collection efficiency
Wherein, the structural formula of all Phosphine ligands L1-L8 is shown in as follows.As can be seen from the above table, when using other Phosphine ligands, productive rate all will be caused sharply to reduce, lost the meaning of research, and demonstrating described Phosphine ligands of the present invention thus, for present method, there is specific catalyzing cooperation effect.
Embodiment 25-32
Replace with respectively except following organic solvent except by organic solvent DMF wherein, implement embodiment 25-32 respectively in the mode identical with embodiment 1-8, with an organic solvent, the yield of embodiment corresponding relation and corresponding product is as shown in table 3 below.
Table 4. organic solvent, corresponding embodiment and products collection efficiency
As can be seen here, the selection of organic solvent also has a certain impact for reaction, wherein use productive rate when chloroform, ether, tetracol phenixin, tetrahydrofuran (THF) (THF) higher, but still have relative to DMF and significantly reduce, the phase product yield of toluene, chlorobenzene, acetone, ethyl acetate is then lower.
In sum, can clearly be found out by above-mentioned all embodiments, when applying the method according to the invention, when especially using described nickel complex as catalyzer and described Phosphine ligands, and select suitable organic solvent, object product can be obtained by aminocompound and organic borate single step reaction, and there is very high productive rate.
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 (8)
1. the synthetic method of aminated compounds shown in a formula (I), described method is specially: using nickel complex as catalyzer, under Phosphine ligands exists and in organic solvent, formula (II) compound and (III) compound react and obtain aminated compounds shown in formula (I);
Wherein R is selected from H, halogen, C
1-C
4alkyl or C
1-C
4alkoxyl group;
Ar is aryl, and described aryl can with 1-5 substituting group, and described substituting group is selected from halogen, C independently of one another
1-C
4alkyl or C
1-C
4alkoxyl group;
R
1be selected from H, halogen or C
1-C
4alkyl;
X is Li, Na or K;
Described nickel complex has following structural formula:
Described Phosphine ligands has following structural formula:
2. synthetic method as claimed in claim 1, is characterized in that: according to a mole meter, formula (II) is 1:1-3 with the ratio of (III) compound.
3. synthetic method as claimed in claim 1, is characterized in that: according to a mole meter, the ratio of formula (II) compound and nickel complex as catalyst agent is 1:0.04-0.1.
4. synthetic method as claimed in claim 1, is characterized in that: according to a mole meter, the ratio of described nickel complex as catalyst agent and Phosphine ligands is 1:2-3.
5. the synthetic method as described in claim 1, is characterized in that: temperature of reaction is 70-110 DEG C; Reaction times is 8-14 hour.
6. synthetic method as claimed in claim 1, is characterized in that: described reaction is carried out under atmosphere of inert gases.
7. synthetic method as claimed in claim 1, is characterized in that: the aftertreatment that reaction terminates is completed by chromatography over CC, and wherein elutriant is the mixture of ethyl acetate and acetone, and both volumes are 1:1-3.
8. the synthetic method as described in any one of claim 1-7, is characterized in that: described organic solvent is dimethyl formamide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410378364.3A CN104098476B (en) | 2014-08-04 | 2014-08-04 | A kind of synthetic method of building the aminated compounds of unit as medicine structure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410378364.3A CN104098476B (en) | 2014-08-04 | 2014-08-04 | A kind of synthetic method of building the aminated compounds of unit as medicine structure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104098476A CN104098476A (en) | 2014-10-15 |
| CN104098476B true CN104098476B (en) | 2015-10-14 |
Family
ID=51667062
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410378364.3A Expired - Fee Related CN104098476B (en) | 2014-08-04 | 2014-08-04 | A kind of synthetic method of building the aminated compounds of unit as medicine structure |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104098476B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105037073B (en) * | 2015-07-13 | 2016-12-28 | 青岛申达众创技术服务有限公司 | A kind of synthetic method of biaryl compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101374799A (en) * | 2006-06-01 | 2009-02-25 | 巴斯夫欧洲公司 | Process for preparing substituted biphenyls |
| CN103342651A (en) * | 2013-07-22 | 2013-10-09 | 温州大学 | Synthesis method of diaryl aniline compound |
-
2014
- 2014-08-04 CN CN201410378364.3A patent/CN104098476B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101374799A (en) * | 2006-06-01 | 2009-02-25 | 巴斯夫欧洲公司 | Process for preparing substituted biphenyls |
| CN103342651A (en) * | 2013-07-22 | 2013-10-09 | 温州大学 | Synthesis method of diaryl aniline compound |
Non-Patent Citations (2)
| Title |
|---|
| Aryl Triolborates: Novel Reagent for Copper-Catalyzed N Arylation of Amines, Anilines, and Imidazoles;Xiao-Qiang Yu, et al.;《Chem.Asian J.》;20080613;第3卷;1517-1522 * |
| Development of an Air-Stable Nickel Precatalyst for the Amination of Aryl Chlorides, Sulfamates, Mesylates, and Triflates;Nathaniel H.Park, et al.;《Org.Lett.》;20131127;第16卷;220-223 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104098476A (en) | 2014-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111704582B (en) | Preparation method of Favipiravir and derivatives thereof | |
| CN104341342B (en) | A kind of high yield, highly purified DAST source powder synthesis technique | |
| WO2011035532A1 (en) | Preparation method of aromatic borate ester compound | |
| CN104230968A (en) | Cadmium-containing dual-core polymer with mixed-ligand and preparation method of cadmium-containing dual-core polymer | |
| CN101264456B (en) | High-efficiency catalyst for catalyzing amine and carbodiimide to process addition reaction and application | |
| Gopi et al. | Synthesis and conformational features of sym N, N′, N ″-triarylguanidines | |
| CN104098476B (en) | A kind of synthetic method of building the aminated compounds of unit as medicine structure | |
| Chen et al. | Structural characterization of the pentamolybdate anion,[(MoO4) 2 {Mo3O8 (OMe)}]-3, and isolation of the [Mo3O8 (OMe)]+ trinuclear core in the squarate complex [{Mo3O8 (OMe)}(C4O4) 2] 3 | |
| CN108368034A (en) | Preparation method for isocyanate compound | |
| CN110878104B (en) | Preparation method of chiral 1, 2-bis (2, 5-diphenylphosphino) ethane | |
| CN102321104A (en) | Alkyl-bridged N-heterocyclic dicarbene metal complex as well as preparation method and application thereof | |
| CN103641674B (en) | Method for preparing diaryl sulfone | |
| CN102241553B (en) | Method for preparing aromatic cross-coupled compound | |
| CN105237580A (en) | Bi-di triazole macrocyclic metal complex and synthesizing method and application thereof | |
| CN105209435A (en) | Pyridine- or pyrazine-containing compounds | |
| Slugovc et al. | Thermodynamically controlled formation of diastereopure three-legged piano-stool complexes. The substitution chemistry of [RuCp (aminophosphinoferrocene)(CH3CN)] PF6 | |
| CN103319526A (en) | Phenol derivative containing (Rp)-2-chiral phosphinate substituent and preparation method thereof | |
| CN103694264B (en) | A kind of Sulfydryl nitrogen heterocyclic compound and preparation method thereof | |
| Tang et al. | Synthesis and X-ray crystal structures of two trinuclear molybdenum clusters coordinated by p-nitrobenzoate: Mo3S4 (dtp) 3 (p-NO2C6H4COO)(L) | |
| CN102295663B (en) | Dianionic guanidine complex of rare earth and lithium and application thereof | |
| CN103242378B (en) | Ferrocenyl pyrimidine pincer ligand and preparation method thereof | |
| CN107011222A (en) | A kind of synthetic method of medicine intermediate carbonyl substituted aryl sulfide compound | |
| CN106543074B (en) | One-dimensional chirality Cu (II) chain complex of one kind and the preparation method and application thereof | |
| CN107827913A (en) | N heterocycle carbine copper containing 1,10 ferrosin shapes（I）Complex and purposes | |
| CN110128373B (en) | Piperazinyl tin complex, preparation method thereof, thin film and solar cell |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: GU XIANGMAO Free format text: FORMER OWNER: ZHUANG WEIPING Effective date: 20150907 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20150907 Address after: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Applicant after: Gu Xiangmao Address before: The village office in Shandong province Weifang City Liyuan 261000 Kuiwei District No. 415 Applicant before: Zhuang Weiping |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Hu Lichun Inventor before: Zhuang Weiping |
|
| COR | Change of bibliographic data | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170113 Address after: 510665 Guangdong city of Guangzhou province Tianhe District Software Park Building No. 59 Middle East block, Grand Building Room 501 Patentee after: Hu Lichun Address before: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Patentee before: Gu Xiangmao |
|
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhou Dong Inventor before: Hu Lichun |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170327 Address after: 101500 Beijing Miyun City Economic Development Zone No. 12 Building No. 1 Teng Lu Yun Patentee after: Beijing Mai Kang Pharmaceutical Co.,Ltd. Address before: 510665 Guangdong city of Guangzhou province Tianhe District Software Park Building No. 59 Middle East block, Grand Building Room 501 Patentee before: Hu Lichun |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20151014 Termination date: 20210804 |