CN104262273B - Synthesis method of 1,3,5-triazine derivatives - Google Patents
Synthesis method of 1,3,5-triazine derivatives Download PDFInfo
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- CN104262273B CN104262273B CN201410458244.4A CN201410458244A CN104262273B CN 104262273 B CN104262273 B CN 104262273B CN 201410458244 A CN201410458244 A CN 201410458244A CN 104262273 B CN104262273 B CN 104262273B
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- triazines
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- amidine
- alcohol
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- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 125000003363 1,3,5-triazinyl group Chemical class N1=C(N=CN=C1)* 0.000 title abstract 4
- 239000002904 solvent Substances 0.000 claims abstract description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 8
- -1 amidine hydrochloride Chemical class 0.000 claims abstract description 7
- 238000004440 column chromatography Methods 0.000 claims abstract description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 4
- 238000001035 drying Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- 239000012043 crude product Substances 0.000 claims description 22
- 150000001409 amidines Chemical class 0.000 claims description 14
- 238000000746 purification Methods 0.000 claims description 14
- 150000000182 1,3,5-triazines Chemical class 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 11
- 238000010189 synthetic method Methods 0.000 claims description 11
- 239000006227 byproduct Substances 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 claims description 4
- 241001597008 Nomeidae Species 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000002024 ethyl acetate extract Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 23
- 230000015572 biosynthetic process Effects 0.000 abstract description 17
- 238000003786 synthesis reaction Methods 0.000 abstract description 17
- 239000000758 substrate Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 abstract 1
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 150000003918 triazines Chemical class 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000003513 alkali Substances 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 2
- NTEIZPBYXABJKN-UHFFFAOYSA-N 2-(4-chlorophenyl)-4,6-diphenyl-1,3,5-triazine Chemical class C1=CC(Cl)=CC=C1C1=NC(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=N1 NTEIZPBYXABJKN-UHFFFAOYSA-N 0.000 description 2
- YRRPMAVQIDXZQN-UHFFFAOYSA-N 2-(4-methoxyphenyl)-4,6-diphenyl-1,3,5-triazine Chemical class C1=CC(OC)=CC=C1C1=NC(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=N1 YRRPMAVQIDXZQN-UHFFFAOYSA-N 0.000 description 2
- ZXTHWIZHGLNEPG-UHFFFAOYSA-N 2-phenyl-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C1=CC=CC=C1 ZXTHWIZHGLNEPG-UHFFFAOYSA-N 0.000 description 2
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- MTDUPZAXNYELOU-UHFFFAOYSA-N hydron;4-methylbenzenecarboximidamide;chloride Chemical compound Cl.CC1=CC=C(C(N)=N)C=C1 MTDUPZAXNYELOU-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000003541 multi-stage reaction Methods 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 description 1
- SIRPHJCQZYVEES-UHFFFAOYSA-N 1-methylbenzimidazole-2-carbaldehyde Chemical compound C1=CC=C2N(C)C(C=O)=NC2=C1 SIRPHJCQZYVEES-UHFFFAOYSA-N 0.000 description 1
- NPNRPQIHDJKWMW-UHFFFAOYSA-N 2,4,6-trinitro-1,3,5-triazine Chemical compound [O-][N+](=O)C1=NC([N+]([O-])=O)=NC([N+]([O-])=O)=N1 NPNRPQIHDJKWMW-UHFFFAOYSA-N 0.000 description 1
- YENJALYDRXJPHB-UHFFFAOYSA-N 2-(2,4-dibromophenyl)-4-(4-propan-2-ylphenyl)-1,3,5-triazine Chemical class CC(C)C1=CC=C(C=C1)C2=NC(=NC=N2)C3=C(C=C(C=C3)Br)Br YENJALYDRXJPHB-UHFFFAOYSA-N 0.000 description 1
- SJVPUWOURQRDHF-UHFFFAOYSA-N 2-(4-methylphenyl)-4,6-diphenyl-1,3,5-triazine Chemical class C1=CC(C)=CC=C1C1=NC(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=N1 SJVPUWOURQRDHF-UHFFFAOYSA-N 0.000 description 1
- YONYPNNXOHWPBZ-UHFFFAOYSA-N 2-methyl-4,6-diphenyl-1,3,5-triazine Chemical class N=1C(C)=NC(C=2C=CC=CC=2)=NC=1C1=CC=CC=C1 YONYPNNXOHWPBZ-UHFFFAOYSA-N 0.000 description 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JKTYGPATCNUWKN-UHFFFAOYSA-N 4-nitrobenzyl alcohol Chemical compound OCC1=CC=C([N+]([O-])=O)C=C1 JKTYGPATCNUWKN-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- IUFUITYPUYMIHI-UHFFFAOYSA-N N-[1-(3,5-dimethylphenoxy)propan-2-yl]-6-(2-fluoropropan-2-yl)-1,3,5-triazine-2,4-diamine Chemical compound N=1C(N)=NC(C(C)(C)F)=NC=1NC(C)COC1=CC(C)=CC(C)=C1 IUFUITYPUYMIHI-UHFFFAOYSA-N 0.000 description 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- UMRSVAKGZBVPKD-UHFFFAOYSA-N acetic acid;copper Chemical compound [Cu].CC(O)=O UMRSVAKGZBVPKD-UHFFFAOYSA-N 0.000 description 1
- QXAITBQSYVNQDR-ZIOPAAQOSA-N amitraz Chemical compound C=1C=C(C)C=C(C)C=1/N=C/N(C)\C=N\C1=CC=C(C)C=C1C QXAITBQSYVNQDR-ZIOPAAQOSA-N 0.000 description 1
- 229960002587 amitraz Drugs 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- ACBQROXDOHKANW-UHFFFAOYSA-N bis(4-nitrophenyl) carbonate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)OC1=CC=C([N+]([O-])=O)C=C1 ACBQROXDOHKANW-UHFFFAOYSA-N 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- JKYMSKUDZIJFKI-UHFFFAOYSA-N cyanuric triazide Chemical compound [N-]=[N+]=NC1=NC(N=[N+]=[N-])=NC(N=[N+]=[N-])=N1 JKYMSKUDZIJFKI-UHFFFAOYSA-N 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- OIGWAXDAPKFNCQ-UHFFFAOYSA-N p-Isopropylbenzyl alcohol Natural products CC(C)C1=CC=C(CO)C=C1 OIGWAXDAPKFNCQ-UHFFFAOYSA-N 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000004449 solid propellant Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000010490 three component reaction Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/24—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to three ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a synthesis method of 1,3,5-triazine derivatives. The synthesis method comprises the steps of mixing amidine hydrochloride, alcohol, hydrated copper acetate and sodium carbonate, adding a solvent, reacting for 12 hours-24 hours in air at the temperature of 110 DEG C-120 DEG C to obtain a product, purifying the product, extracting, drying, concentrating and separating by virtue of column chromatography to obtain the 1,3,5-triazine derivatives. The synthesis method of the 1,3,5-triazine derivatives, which is disclosed by the invention has the advantages of low cost, available raw materials, high synthesis efficiency and wide application range and is suitable for reaction of a plurality of substrates.
Description
Technical field
The invention belongs to technical field of organic synthesis, particularly to a kind of synthetic method of triazine derivative.
Background technology
The research of triazine derivative starts from the 1950's mid-term, develops first triazine herbicide west at that time
Agate Tianjin makes crops obtain large-scale harvest.Hereafter abroad tens of kinds of such compound in triazine class have been developed, mainly
For weeding, parasite killing, sterilization and antiviral etc., such as triaziflam, 1,3,5-triazines -2,4- diketone, prometryn and Garagard
Deng.This kind of toxicity of compound is low, and residual is short, and mechanism of action is unique, is even more the extensive pass being subject to domestic and international research worker in recent years
Note.Additionally, triaizine compounds ring strain is less, stability is fine, and nitrogen content high (51.83%) has the higher enthalpy of formation,
And such compound has the advantages that high density, heat stability are good, therefore can fire as gas-forming agent, solid propellant
Material and pyrotechnic compound.1,3,5- triazine (tct) as chloro- in 2,4,6- tri-, 2,4,6- triazido -1,3,5- triazine (tat) and 2,
4,6- trinitro- -1,3,5- triazine (tnta) etc. is good energetic material.Therefore, explore 1,3,5-triazines analog derivative
Synthesis, biological activity are most one of research topics of vitality in organic chemistry.
The method of the synthesis of triazine compound reported in document mainly has following several:
(1) reacted under microwave with isosulfocyanate compound and amidine and obtain 1,3,5- compound in triazine class.
This method employs microwave condition, and the alkali used is the highly basic such as naoh, and yield is not high, and industrial enforcement is more tired
Difficult.
(2) with isosulfocyanate compound and n, react under n- diethyl amidine compound room temperature in thf solvent
24h obtains intermediate product, then with hgcl2For catalyst, triethanolamine is alkali, reacts 4h at room temperature with the hydrochlorate of amidine and obtains
1,3,5- triazine derivative.
Although the method is carried out at room temperature, use hgcl2 this severe toxicity class material and do catalyst, and the product obtaining
Produce rate is all not ideal.
(3) make catalyst using ru coordination compound, amidine obtains 1,3,5-triazines with alcohol reaction.
This reaction is to make catalyst with noble metal ru coordination compound, and the alkali used is cs2co3, reaction cost height, it is unfavorable for
Industrial mass production.
(4) reacted with dmf with the hydrochlorate of amidine and obtain 1,3,5- compound in triazine class.
The method use pyridine and do part, and need the o of 1atm2Condition, reaction is more harsh, and substrate is applicable
Property is not high, and yield is also undesirable.
(5) carry out three component reaction and obtain containing 1,3,5- triazine with cyanamide and triethyl orthoformate with 1,2,4- triazole
The material of structure.
This reaction employs microwave reaction, and reaction temperature is higher, and yield is general, is unfavorable for commercial production.
(6) carry out multistep reaction using p-nitrophenyl carbonate resin and obtain 1,3,5- triazine derivative.
(i) s- methyl-isourea (6equiv, 0.1m), cs2co3(12equiv, 0.2m), dmf, room temperature, 48h.
(ii)r1Nco (6equiv, 0.1m), dcm, room temperature, a night.(iii)r2nh2(6equiv, 0.1m), thf, 50 DEG C, a night.
(iv) koet (3equiv, 0.1m), etoh, 60 DEG C, a night.(v) tfa/dcm (1:1), 1h.The method is multistep reaction, this
Determine final product yield not high.
The method that prior art synthesizes 1,3,5-triazines class compound is a lot, but some needs of these methods are through complicated
Synthesis step, side reaction is more, and most of productivity ratio is relatively low；Some are easily caused using highly toxic substrate or organic solvent
Environmental pollution, some use rare earth metal etc. is catalyst, and cost costly, is not suitable for commercial production.Therefore it provides one
The new green synthesis method of kind of synthesis 1,3,5- compound in triazine class is necessary.
Content of the invention
For the deficiencies in the prior art, it is an object of the invention to provide a kind of synthesis side of 1,3,5-triazines analog derivative
Method, it is oxidant, acetic acid copper catalysis amidine and alcohol direct reaction that the present invention utilizes air, synthetic method low cost of the present invention, raw material
It is easy to get, efficiency high, range is wide, is suitable for multiple substrate reactions.
The technical solution used in the present invention is:
A kind of synthetic method of 1,3,5-triazines derivant, step includes:
A, the hydrochlorate of amidine, alcohol are mixed with copper acetate monohydrate, sodium carbonate after, add solvent, at 110 DEG C -120 DEG C
Under the conditions of in the air reaction 12h-24h；
B, by product purification, through extraction, be dried, concentrate after 1,3,5-triazines analog derivative is obtained by column chromatography for separation.
The structural formula of the hydrochlorate of described amidine is:
Wherein r is h, br, ch3；
The structural formula of described alcohol is:
Wherein r is selected from h, ch3、ch3ch2ch2、(ch3)2ch、ph、2-ch3-c6h4、3-ch3-c6h4、4-ch3-c6h4、4-
och3-c6h4、2-cl-c6h4、3-cl-c6h4、4-cl-c6h4、4-br-c6h4、4-f-c6h4、4-cf3-c6h4、2-no2-c6h4、3-
no2-c6h4、4-no2-c6h4、4-(ch3)2ch-c6h4One of；
The hydrochlorate of described amidine, alcohol, copper acetate monohydrate, the amount ratio of the material of sodium carbonate are: 2:(1-1.5): 0.2:2；
The hydrochlorate of described amidine concentration in a solvent is: 0.40-0.67mol/l；
Described solvent is toluene；
Purification in described step b particularly as follows: products therefrom is extracted with ethyl acetate, anhydrous sodium sulfate drying, decompression dense
Contracting, obtain crude product, with volume ratio as petroleum ether: the mixed solvent of ethyl acetate=80-100:1 as developing solvent, by column chromatography
Separate and obtain 1,3,5- compound in triazine class.
A kind of synthetic method of 1,3,5-triazines derivant that the present invention provides, compared with prior art, has the advantage that
(1) carry out in air atmosphere, low cost；(2) not using noble metal, highly basic and organic oxidizing agent, but using a hydration
Schweinfurt green makees catalyst, cost-effective；(3) amidine and alcohol is utilized to be reaction raw materials, raw material is easy to get；(4) this synthetic method efficiency high,
Range is wide, is suitable for multiple substrate reactions.
Specific embodiment
Embodiment 1
The synthesis of 2,4,6- triphenyls -1,3,5-triazines, comprises the following steps:
Take 20mmol benzamidine hydrochlorid and 12mmol benzyl alcohol in the round-bottomed flask of 100ml, then add 2mmolcu toward it
(oac)2·h2O, 20mmol na2co3And 30ml toluene, stirring reaction after 24 hours at 110 DEG C, by product acetic acid second
Ester is extracted, and is dried to obtain crude product, by crude product purified by silica gel column chromatography (solvent volume is than for petroleum ether: ethyl acetate=
100:1) purification obtains white solid is 2,4,6- triphenyls -1,3,5-triazines, yield 88%, and fusing point is 238 DEG C.
1h nmr(300mhz,cdcl3)δ8.80-8.78(m,6h),7.65-7.56(m,9h)；
13c nmr(75mhz,d6-dmso)δ166.6,134.6,129.8,128.9.
Embodiment 2
The synthesis of 2- (4- chlorphenyl) -4,6- diphenyl -1,3,5-triazines, comprises the following steps:
Take 20mmol benzamidine hydrochlorid and 13mmol 4- chlorobenzene methanol in the round-bottomed flask of 100ml, then toward its addition
2mmolcu(oac)2·h2O, 20mmol na2co3And 30ml toluene, stirring reaction after 12 hours at 110 DEG C, by product
Extracted with ethyl acetate, be dried to obtain crude product, (solvent volume is than for petroleum ether: second by crude product purified by silica gel column chromatography
Acetoacetic ester=80:1) to obtain white solid be 2- (4- chlorphenyl) -4,6- diphenyl -1,3,5-triazines to purification, yield 88%, fusing point
For 198 DEG C.
1h nmr(300mhz,cdcl3)δ8.74-8.66(m,6h),7.59-7.50(m,8h)；
13c nmr(75mhz,cdcl3)δ172.0,171.0,139.1,136.4,135.1,133.0,130.6,129.3,
129.3,129.0.
Embodiment 3
The synthesis of 2,4- diphenyl -6- p-methylphenyls -1,3,5-triazines, comprises the following steps:
Take 20mmol benzamidine hydrochlorid and 14mmol 4- methylbenzyl alcohol in the round-bottomed flask of 100ml, then toward its addition
2mmol cu(oac)2·h2O, 20mmol na2co3And 30ml toluene, stirring reaction after 24 hours at 110 DEG C, by product
Extracted with ethyl acetate, be dried to obtain crude product, (solvent volume is than for petroleum ether: second by crude product purified by silica gel column chromatography
Acetoacetic ester=100:1) to obtain white solid be 2,4- diphenyl -6- p-methylphenyl -1,3,5-triazines to purification, yield 88%, fusing point
For 196 DEG C.
1h nmr(300mhz,cdcl3) δ 8.72 (d, j=6.0hz, 4h), 8.60 (d, j=7.8hz, 2h), 7.53 (d, j
=6.6hz, 6h), 7.3 (d, j=7.8hz, 2h)；
13c nmr(75mhz,d6-dmso)δ171.9,171.8,143.5,136.7,133.9,132.8,129.8,
129.3,129.0,22.2.
Embodiment 4
The synthesis of 2,4- diphenyl -6- (4- trifluoromethyl) -1,3,5-triazines, comprises the following steps:
Take 20mmol benzamidine hydrochlorid and 12mmol4- trifluoromethyl benzyl alcohol in the round-bottomed flask of 100ml, then toward it
Add 2mmol cu (oac)2·h2O, 20mmol na2co3And 30ml toluene, at 110 DEG C, stirring reaction, will after 18 hours
Product is extracted with ethyl acetate, is dried to obtain crude product, and by crude product purified by silica gel column chromatography, (solvent volume is than for oil
Ether: ethyl acetate=90:1) to obtain white solid be 2,4- diphenyl -6- (4- trifluoromethyl) -1,3,5-triazines to purification, produce
Rate 87%, fusing point is 183 DEG C.
1h nmr(300mhz,cdcl3) δ 8.84 (d, j=8.1hz, 2h), 8.76-8.73 (m, 4h), 7.81 (d, j=
8.1hz,2h),7.66-7.55(m,6h)；
13c nmr(75mhz,cdcl3)δ172.0,170.6,139.8,136.1,134.3,133.1,129.5,129.3,
129.0,125.8,125.8.
Embodiment 5
The synthesis of 2- (4- methoxyphenyl) -4,6- diphenyl -1,3,5-triazines, comprises the following steps:
Take 20mmol benzamidine hydrochlorid and 15mmol4- methoxy benzyl alcohol in the round-bottomed flask of 100ml, then toward itself plus
Enter 2mmol cu (oac)2·h2O, 20mmol na2co3And 30ml toluene, at 110 DEG C, stirring reaction, after 24 hours, will be produced
Thing is extracted with ethyl acetate, is dried to obtain crude product, by crude product purified by silica gel column chromatography (solvent volume is than for petroleum ether:
Ethyl acetate=80:1) to obtain white solid be 2- (4- methoxyphenyl) -4,6- diphenyl -1,3,5-triazines to purification, yield
91%, fusing point is 160 DEG C.
1h nmr(300mhz,cdcl3) δ 8.78-8.73 (m, 6h), 7.62-7.55 (m, 6h), 7.07 (d, j=8.7hz,
2h),3.92(s,3h)；
13c nmr(75mhz,d6-dmso)δ171.5,164.1,136.3,133.8,131.5,129.8,129.4,
128.4,115.2,56.4.
Embodiment 6
The synthesis of 2- (4- nitrobenzophenone) -4,6- diphenyl -1,3,5-triazines, comprises the following steps:
Take 20mmol benzamidine hydrochlorid and 14mmol 4- nitrobenzyl alcohol in the round-bottomed flask of 100ml, then toward its addition
2mmol cu(oac)2·h2O, 20mmol na2co3And 50ml toluene, stirring reaction after 12 hours at 110 DEG C, by product
Extracted with ethyl acetate, be dried to obtain crude product, (solvent volume is than for petroleum ether: second by crude product purified by silica gel column chromatography
Acetoacetic ester=100:1) to obtain white solid be 2- (4- nitrobenzophenone) -4,6- diphenyl -1,3,5-triazines to purification, yield 46%,
Fusing point is 217 DEG C.
1h nmr(300mhz,cdcl3) δ 8.93 (d, j=8.7hz, 2h), 8.78-8.75 (m, 4h), 8.41 (d, j=
9.0hz,2h),7.68-7.57(m,6h)；
13c nmr(75mhz,cdcl3)δ172.4,170.3,136.0,133.4,130.2,129.4,129.2,124.1.
Embodiment 7
2- phenyl -4, the synthesis of 6- bis--p-methylphenyl -1,3,5-triazines, comprise the following steps:
Take 20mmol 4- methyl Amidinobenzene hydrochloride and 13mmol benzyl alcohol in the round-bottomed flask of 100ml, then toward itself plus
Enter 2mmol cu (oac)2·h2O, 20mmol na2co3And 30ml toluene, at 110 DEG C, stirring reaction, after 24 hours, will be produced
Thing is extracted with ethyl acetate, is dried to obtain crude product, by crude product purified by silica gel column chromatography (solvent volume is than for petroleum ether:
Ethyl acetate=100:1) to obtain white solid be 2- phenyl -4 to purification, 6- bis--p-methylphenyl -1,3,5-triazines, yield 87%, melt
Point is 233 DEG C.
1h nmr(300mhz,cdcl3) δ 8.77 (d, j=6.0hz, 2h), 8.66 (d, j=8.1hz, 4h), 7.63-7.55
(m, 3h), 7.37 (d, j=7.8hz, 4h)；
13c nmr(75mhz,cdcl3)δ171.9,171.8,143.4,136.8,134.0,132.7,129.7,129.3,
129.3,128.9,22.1.
Embodiment 8
The synthesis of 2,4,6- tri--p-methylphenyls -1,3,5-triazines, comprises the following steps:
Take 20mmol 4- methyl Amidinobenzene hydrochloride and 12mmol 4- methylbenzyl alcohol in the round-bottomed flask of 100ml,
Add 2mmol cu (oac) toward it again2·h2O, 20mmol na2co3And 30ml toluene, at 110 DEG C, stirring reaction 24 is little
Shi Hou, product is extracted with ethyl acetate, is dried to obtain crude product, by crude product purified by silica gel column chromatography (solvent volume ratio
For petroleum ether: ethyl acetate=100:1) to obtain white solid be 2,4,6- tri--p-methylphenyls -1,3,5-triazines to purification, yield
86%, fusing point is 321 DEG C.
1h nmr(300mhz,cdcl3) δ 8.65 (d, j=6.3hz, 6h), 7.36 (d, j=6.3hz, 6h), 2.47 (s,
9h)；
13c nmr(75mhz,cdcl3)δ171.7,143.2,134.1,129.7,129.3,22.1.
Embodiment 9
The synthesis of 2,4- dibromo phenyl -6- (4- isopropyl phenyl) -1,3,5-triazines, comprises the following steps:
Take 20mmol 4- bromobenzene amitraz hydrochloride and 14mmol 4- isopropylbenzyl alcohol in the round-bottomed flask of 100ml,
Add 2mmol cu (oac) toward it again2·h2O, 20mmol na2co3And 30ml toluene, at 120 DEG C, stirring reaction 24 is little
Shi Hou, product is extracted with ethyl acetate, is dried to obtain crude product, by crude product purified by silica gel column chromatography (solvent volume ratio
For petroleum ether: ethyl acetate=100:1) to obtain white solid be 2,4- dibromo phenyl -6- (4- isopropyl phenyl) -1,3,5- to purification
Triazine, yield 66%, fusing point is 181 DEG C.
1h nmr(300mhz,cdcl3) δ 8.59-8.52 (m, 6h), 7.65 (d, j=8.1hz, 4h), 7.40 (d, j=
8.4hz, 2h), 3.10-2.97 (m, 1h), 1.34 (d, j=6.9hz, 6h)；
13c nmr(75mhz,cdcl3)δ172.1,170.0,154.6,135.4,133.8,132.2,130.7,129.5,
127.9,127.2,34.7,24.2.
Embodiment 10
2- methyl -4, the synthesis of 6- diphenyl -1,3,5-triazines, comprise the following steps:
Take 20mmol benzamidine hydrochlorid and 14mmol ethanol in the round-bottomed flask of 100ml, then add 2mmolcu toward it
(oac)2·h2O, 20mmol na2co3And 30ml toluene, stirring reaction after 24 hours at 110 DEG C, by product acetic acid second
Ester is extracted, and is dried to obtain crude product, by crude product purified by silica gel column chromatography (solvent volume is than for petroleum ether: ethyl acetate=
100:1) purification white solid is 2- methyl -4,6- diphenyl -1,3,5-triazines, yield 63%, and fusing point is 80 DEG C.
1h nmr(300mhz,cdcl3)δ8.58-8.55(m,4h),7.51-7.46(m,6h),2.71(s,3h)；
13c nmr(75mhz,cdcl3)δ177.4,171.6,136.3,132.9,129.3,129.2,26.5.
The above be only the preferred embodiment of the present invention it should be pointed out that: for a person skilled in the art,
Without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications, all should be considered as this
The protection domain of invention.
Claims (5)
1. a kind of synthetic method of 1,3,5-triazines derivant, step includes:
A, the hydrochlorate of amidine, alcohol are mixed with copper acetate monohydrate, sodium carbonate after, add solvent, in 110 DEG C -120 DEG C of condition
Lower in the air reacts 12h-24h；
B, by product purification, through extraction, be dried, concentrate after 1,3,5-triazines analog derivative is obtained by column chromatography for separation；
The hydrochlorate structural formula of described amidine is:
Wherein r is h, br, ch3；
The structural formula of described alcohol is:
Wherein: r is selected from h, ch3、ch3ch2ch2、(ch3)2ch、ph、2-ch3-c6h4、3-ch3-c6h4、4-ch3-c6h4、4-och3-
c6h4、2-cl-c6h4、3-cl-c6h4、4-cl-c6h4、4-br-c6h4、4-f-c6h4、4-cf3-c6h4、2-no2-c6h4、3-no2-
c6h4、4-no2-c6h4、4-(ch3)2ch-c6h4One of.
2. synthetic method as claimed in claim 1 it is characterised in that: the hydrochlorate of described amidine, alcohol, copper acetate monohydrate, carbon
The amount ratio of the material of sour sodium is: 2:(1-1.5): 0.2:2.
3. synthetic method as claimed in claim 1 it is characterised in that: the hydrochlorate of described amidine concentration in a solvent is:
0.40-0.67mol/l.
4. synthetic method as claimed in claim 1 it is characterised in that: described solvent be toluene.
5. synthetic method as claimed in claim 1 it is characterised in that: purification in described step b is particularly as follows: use products therefrom
Ethyl acetate extracts, anhydrous sodium sulfate drying, and concentrating under reduced pressure obtains crude product, with volume ratio as petroleum ether: ethyl acetate=80-
The mixed solvent of 100:1 is developing solvent, obtains 1,3,5-triazines class compound by column chromatography for separation.
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| CN108409672B (en) * | 2018-03-28 | 2020-01-10 | 安徽师范大学 | Method for synthesizing polysubstituted pyrimidine under catalysis of copper salt |
| CN109810069B (en) * | 2019-03-27 | 2020-10-30 | 郑州轻工业学院 | Preparation method of polysubstituted 1,3, 5-triazine |
| CN110054593B (en) * | 2019-05-16 | 2022-07-08 | 南京工业大学 | Method for synthesizing 1,3, 5-triazine derivative |
| CN110407759A (en) * | 2019-07-04 | 2019-11-05 | 深圳市格物致欣化学技术有限公司 | 1,3,5 replace triaizine compounds and preparation method thereof |
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