CN104910095A - Preparation method of 4-substituted-2-aminothiazole compound - Google Patents
Preparation method of 4-substituted-2-aminothiazole compound Download PDFInfo
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- -1 4-substituted-2-aminothiazole compound Chemical class 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 11
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 claims abstract description 11
- 229940116357 potassium thiocyanate Drugs 0.000 claims abstract description 10
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- 230000035484 reaction time Effects 0.000 claims abstract description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims abstract description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims abstract description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims abstract description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical group CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 9
- 239000012044 organic layer Substances 0.000 claims description 3
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 5
- 239000007787 solid Substances 0.000 description 32
- PYSJLPAOBIGQPK-UHFFFAOYSA-N 4-phenyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1 PYSJLPAOBIGQPK-UHFFFAOYSA-N 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 13
- RLFSDDJVTKEUBW-UHFFFAOYSA-N 5-azido-5-ethenylcyclohexa-1,3-diene Chemical compound [N-]=[N+]=NC1(C=C)CC=CC=C1 RLFSDDJVTKEUBW-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000010189 synthetic method Methods 0.000 description 6
- NBQUWOCIFFHZTM-UHFFFAOYSA-N 4-naphthalen-1-yl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C3=CC=CC=C3C=CC=2)=C1 NBQUWOCIFFHZTM-UHFFFAOYSA-N 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- HBAOQMFTWSDKDV-UHFFFAOYSA-N 4-(2-bromophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=CC=CC=2)Br)=C1 HBAOQMFTWSDKDV-UHFFFAOYSA-N 0.000 description 3
- PDNKBFMOKUBDDR-UHFFFAOYSA-N 4-(3-bromophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(Br)C=CC=2)=C1 PDNKBFMOKUBDDR-UHFFFAOYSA-N 0.000 description 3
- CHBDOPARQRNCDM-UHFFFAOYSA-N 4-(3-nitrophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(C=CC=2)[N+]([O-])=O)=C1 CHBDOPARQRNCDM-UHFFFAOYSA-N 0.000 description 3
- ZBRNKOLWXWMLTA-UHFFFAOYSA-N 4-(4-bromophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC(Br)=CC=2)=C1 ZBRNKOLWXWMLTA-UHFFFAOYSA-N 0.000 description 3
- ARLHWYFAPHJCJT-UHFFFAOYSA-N 4-(4-methylphenyl)-1,3-thiazol-2-amine Chemical compound C1=CC(C)=CC=C1C1=CSC(N)=N1 ARLHWYFAPHJCJT-UHFFFAOYSA-N 0.000 description 3
- CLRFMMYTJJVQRI-UHFFFAOYSA-N 4-(anilinomethyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(CNC=2C=CC=CC=2)=C1 CLRFMMYTJJVQRI-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- BZMHWDRSBWYALX-UHFFFAOYSA-L dichlorocobalt tetrahydrate Chemical compound O.O.O.O.Cl[Co]Cl BZMHWDRSBWYALX-UHFFFAOYSA-L 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VPENSQHVCZUIBR-UHFFFAOYSA-N 1-(1-azidoethenyl)-2-bromobenzene Chemical compound N(=[N+]=[N-])C(=C)C1=C(C=CC=C1)Br VPENSQHVCZUIBR-UHFFFAOYSA-N 0.000 description 1
- SSMWDALECHYMGP-UHFFFAOYSA-N 1-(1-azidoethenyl)-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(C(=C)N=[N+]=[N-])=C1 SSMWDALECHYMGP-UHFFFAOYSA-N 0.000 description 1
- SNAAUGBFFVRPBH-UHFFFAOYSA-N 1-(1-azidoethenyl)-4-bromobenzene Chemical compound BrC1=CC=C(C(=C)N=[N+]=[N-])C=C1 SNAAUGBFFVRPBH-UHFFFAOYSA-N 0.000 description 1
- HJTMLKUQGRHHBV-UHFFFAOYSA-N 1-(1-azidoethenyl)naphthalene Chemical compound C1=CC=C2C(C(N=[N+]=[N-])=C)=CC=CC2=C1 HJTMLKUQGRHHBV-UHFFFAOYSA-N 0.000 description 1
- YIWGJFPJRAEKMK-UHFFFAOYSA-N 1-(2H-benzotriazol-5-yl)-3-methyl-8-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione Chemical compound CN1C(=O)N(c2ccc3n[nH]nc3c2)C2(CCN(CC2)C(=O)c2cnc(NCc3cccc(OC(F)(F)F)c3)nc2)C1=O YIWGJFPJRAEKMK-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- QLVLHVNIDBKBQA-UHFFFAOYSA-N BrC1=CC=CC(C(=C)N=[N+]=[N-])=C1 Chemical compound BrC1=CC=CC(C(=C)N=[N+]=[N-])=C1 QLVLHVNIDBKBQA-UHFFFAOYSA-N 0.000 description 1
- IREDZAIGTJEZEC-UHFFFAOYSA-N C1(=CC=CC=C1)C=1N=C(SC1)N.C1(=CC=CC=C1)C=1N=C(SC1)N Chemical compound C1(=CC=CC=C1)C=1N=C(SC1)N.C1(=CC=CC=C1)C=1N=C(SC1)N IREDZAIGTJEZEC-UHFFFAOYSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
- MQRWBMAEBQOWAF-UHFFFAOYSA-N acetic acid;nickel Chemical compound [Ni].CC(O)=O.CC(O)=O MQRWBMAEBQOWAF-UHFFFAOYSA-N 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940041010 fourth-generation cephalosporins Drugs 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229940078494 nickel acetate Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940041007 third-generation cephalosporins Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
Description
技术领域technical field
本发明涉及一种4-取代-2-氨基噻唑化合物的制备方法，即烯烃叠氮在醋酸钯的催化下与硫氰酸钾发生反应得到4-取代-2-氨基噻唑化合物。The invention relates to a preparation method of a 4-substituted-2-aminothiazole compound, that is, olefin azide reacts with potassium thiocyanate under the catalysis of palladium acetate to obtain a 4-substituted-2-aminothiazole compound.
背景技术Background technique
氨基噻唑化合物是重要的含氮杂环化合物，近年来被广泛应用于工业生产、药物研发等多个领域。其中4-取代-2-氨基噻唑化合物常常作为医药、染料、净水剂等的合成中间体，在第三、四代头孢菌素的合成中应用广泛。4-取代-2-氨基噻唑化合物因为具有重要的应用价值，其合成方法一直受到广泛的关注，其中最为经典的是Hantzsch等提出的噻唑合成法(Hantzsch,A.；Weber,J.H.Chemische Berichte.1887,20,3118)，它以α-卤代酮和硫脲作用，得到4-取代-2-氨基噻唑化合物(式1)。Aminothiazole compounds are important nitrogen-containing heterocyclic compounds, which have been widely used in many fields such as industrial production and drug research and development in recent years. Among them, 4-substituted-2-aminothiazole compounds are often used as synthetic intermediates of medicines, dyes, water purifiers, etc., and are widely used in the synthesis of third and fourth generation cephalosporins. 4-substituted-2-aminothiazole compound is because of having important application value, and its synthetic method has been widely paid attention to, wherein the most classic is the thiazole synthetic method proposed by Hantzsch etc. (Hantzsch, A.; Weber, J.H.Chemische Berichte.1887 , 20,3118), it reacts with α-halogenated ketone and thiourea to obtain 4-substituted-2-aminothiazole compound (Formula 1).
该方法存在反应时间较长，大量使用挥发性有毒有机溶剂，产率较低等缺点。同时该合成方法通常采用原料α-卤代酮，α-卤代酮的制备需要与卤素发生取代反应，如果底物中含有碳碳不饱和键，就会与卤素发生加成反应受到破坏，因此传统的4-取代-2-氨基噻唑合成方法对于含有碳碳不饱和键的底物通常是不适用的。This method has the disadvantages of long reaction time, large use of volatile toxic organic solvents, and low yield. Simultaneously, this synthetic method usually adopts raw material α-halogenated ketones, and the preparation of α-halogenated ketones requires a substitution reaction with a halogen. If the substrate contains a carbon-carbon unsaturated bond, the addition reaction with the halogen will be destroyed, so The traditional synthesis method of 4-substituted-2-aminothiazoles is usually not suitable for substrates containing carbon-carbon unsaturated bonds.
发明内容Contents of the invention
本发明要解决的技术问题是提供一种4-取代-2-氨基噻唑化合物的制备方法，该方法对于底物含有碳碳不饱和键的情况同样适用。The technical problem to be solved by the present invention is to provide a preparation method of 4-substituted-2-aminothiazole compound, which is also applicable to the case where the substrate contains carbon-carbon unsaturated bonds.
为了解决上述技术问题，本发明提供一种4-取代-2-氨基噻唑化合物的制备方法：在溶剂中，如式Ⅰ所示的烯烃叠氮在醋酸钯的催化下与硫氰酸钾发生反应得到4-取代-2-氨基噻唑化合物；烯烃叠氮类化合物、硫氰酸钾、醋酸钯的摩尔比为20：59～61：1(较佳为20：60：1)；反应温度为75～85℃(较佳为80℃)，反应时间为11～13小时(较佳为12小时)；In order to solve the above-mentioned technical problem, the present invention provides a kind of preparation method of 4-substituted-2-aminothiazole compound: in solvent, olefin azide as shown in formula I reacts with potassium thiocyanate under the catalysis of palladium acetate Obtain 4-substituted-2-aminothiazole compound; the molar ratio of olefin azide compound, potassium thiocyanate and palladium acetate is 20:59～61:1 (preferably 20:60:1); the reaction temperature is 75 ~85°C (preferably 80°C), the reaction time is 11-13 hours (preferably 12 hours);
式Ⅰ中：R1为苯基、2-溴苯基、3-溴苯基、4-溴苯基、4-甲基苯基、4-乙氧基-3-溴苯基、3-硝基苯基、4-甲氧酰基苯基、1-萘基、苯胺基甲基或反式-4-(3-苯基烯丙基氧甲基)。In formula Ⅰ: R 1 is phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-methylphenyl, 4-ethoxy-3-bromophenyl, 3-nitrate phenyl, 4-methoxyacylphenyl, 1-naphthyl, anilinomethyl or trans-4-(3-phenylallyloxymethyl).
作为本发明的4-取代-2-氨基噻唑化合物的制备方法的改进，其包括以下步骤：As an improvement of the preparation method of the 4-substituted-2-aminothiazole compound of the present invention, it comprises the following steps:
1)、将烯烃叠氮化合物(Ⅰ)、硫氰酸钾(Ⅱ)和醋酸钯(Ⅲ)分别加入溶剂中进行上述反应；1), adding olefin azide compound (I), potassium thiocyanate (II) and palladium acetate (III) into the solvent respectively to carry out the above reaction;
每1mmol的烯烃叠氮配用1.5～2.5ml(例如为2.0ml)的溶剂；Use 1.5-2.5ml (for example, 2.0ml) of solvent per 1mmol of olefin azide;
2)、步骤1)所得的反应液旋干(经旋转蒸发仪)后，用乙酸乙酯萃取，所得的有机层(位于上层)经洗涤(用饱和食盐水洗涤)后、干燥、浓缩(经旋转蒸发仪)；2), the reaction solution obtained in step 1) was spin-dried (via a rotary evaporator), extracted with ethyl acetate, and the obtained organic layer (located in the upper layer) was washed (washed with saturated brine), dried, and concentrated (via Rotary evaporator);
3)、将步骤2)所得浓缩物进行硅胶柱层析，得4-取代-2-氨基噻唑化合物。3), the concentrate obtained in step 2) is subjected to silica gel column chromatography to obtain a 4-substituted-2-aminothiazole compound.
作为本发明的4-取代-2-氨基噻唑化合物的制备方法的进一步改进：溶剂为正丙醇。As a further improvement of the preparation method of the 4-substituted-2-aminothiazole compound of the present invention: the solvent is n-propanol.
本发明通过Pd(OAc)2作催化剂合成了4-取代-2-氨基噻唑化合物(如式2所示)：The present invention has synthesized 4-substituted-2-aminothiazole compound (as shown in formula 2 ) by Pd(OAc) as catalyst:
所得的目标物(Ⅳ)为4-取代-2-氨基噻唑化合物。The obtained object (IV) is a 4-substituted-2-aminothiazole compound.
本发明的4-取代-2-氨基噻唑化合物合成方法具有以下特点：The 4-substituted-2-aminothiazole compound synthetic method of the present invention has the following characteristics:
(1)本方法所用催化剂用量很少，经济高效；(1) the used catalyst consumption of this method is seldom, economical and efficient;
(2)反应温度温和，不需要高温回流，安全方便；(2) The reaction temperature is mild, no high-temperature reflux is required, and it is safe and convenient;
(3)产率高，大部分产物收率在55％以上。(3) The yield is high, and most of the product yields are above 55%.
(4)本合成方法对于底物含有碳碳不饱和键的情况同样适用，克服了传统方法的缺点，本发明的合成方法未见文献报道。(4) This synthetic method is equally applicable to the situation that the substrate contains carbon-carbon unsaturated bonds, and overcomes the shortcomings of traditional methods. The synthetic method of the present invention has no bibliographical information.
具体实施方式Detailed ways
下面将通过实施例对本发明作进一步的说明。The present invention will be further described below through embodiment.
实施例1、 4-苯基-2-氨基噻唑(m1)Embodiment 1, 4-phenyl-2-aminothiazole (m1)
将1-叠氮苯乙烯145.2mg(1mmol)、硫氰酸钾291.5mg(3mmol)，加至反应瓶中，后加入CH3CH2CH2OH(正丙醇)2.0ml，醋酸钯11.2mg(0.05mmol)，加料完毕后，80℃搅拌反应12小时，TLC检测反应(石油醚：乙酸乙酯＝1:1的体积比)。Add 145.2 mg (1 mmol) of 1-azidostyrene and 291.5 mg (3 mmol) of potassium thiocyanate to the reaction flask, then add 2.0 ml of CH 3 CH 2 CH 2 OH (n-propanol) and 11.2 mg of palladium acetate (0.05mmol), after the addition was completed, the reaction was stirred at 80°C for 12 hours, and the reaction was detected by TLC (petroleum ether:ethyl acetate=1:1 volume ratio).
反应结束后，反应液经旋转蒸发仪旋干后，用3×20mL乙酸乙酯萃取三次，有机层(位于上层)合并并用3*30mL饱和食盐水洗涤三次，然后用无水硫酸钠(2.0g)干燥30分钟，旋转蒸发仪浓缩，柱层析(石油醚：乙酸乙酯＝3:1的体积比)，得到产物4-苯基-2-氨基噻唑158.6mg，收率90％。After the reaction, the reaction solution was spin-dried by a rotary evaporator, extracted three times with 3×20mL ethyl acetate, the organic layer (located on the upper layer) was combined and washed three times with 3*30mL saturated brine, and then washed with anhydrous sodium sulfate (2.0g ) was dried for 30 minutes, concentrated by a rotary evaporator, and column chromatographed (petroleum ether: ethyl acetate = 3:1 volume ratio) to obtain 158.6 mg of the product 4-phenyl-2-aminothiazole with a yield of 90%.
所述柱层析具体为：将浓缩液上硅胶柱(内装200目的硅胶80g)，洗脱液(石油醚：乙酸乙酯＝3:1的体积比)的流速为3mL/min；收集第30min～第40min的洗脱液；然后经旋转蒸发仪除去溶剂后，得到产物4-苯基-2-氨基噻唑(2-氨基-4-苯基噻唑)158.6mg，收率90％。The column chromatography is specifically as follows: put the concentrated solution on a silica gel column (80 g of 200 mesh silica gel inside), and the flow rate of the eluent (petroleum ether: ethyl acetate = 3:1 volume ratio) is 3 mL/min; ~The eluent at the 40th minute; after removing the solvent by a rotary evaporator, 158.6 mg of the product 4-phenyl-2-aminothiazole (2-amino-4-phenylthiazole) was obtained, with a yield of 90%.
该4-苯基-2-氨基噻唑的结构式为：The structural formula of this 4-phenyl-2-aminothiazole is:
Pale yellow solid；mp:151.6-152.2℃；1H NMR(500MHz,CDCl3)δ7.77(d,J＝7.28,2H),7.38(t,J＝7.63,2H),7.29(t,J＝7.36,1H),6.72(s,1H),5.34(s,2H)；HRMS(ESI):m/z calcd forC9H8N2S[M+H]+:177.0486,found:177.0489。Pale yellow solid; mp: 151.6-152.2℃; 1 H NMR (500MHz, CDCl 3 ) δ7.77(d, J=7.28, 2H), 7.38(t, J=7.63, 2H), 7.29(t, J= 7.36,1H),6.72(s,1H),5.34(s,2H); HRMS(ESI):m/z calcd for C 9 H 8 N 2 S[M+H] + :177.0486,found:177.0489.
以下为不同条件的对照实验：The following are control experiments under different conditions:
对比例1-1、用七水合硫酸亚铁代替醋酸钯，摩尔量改成0.5mmol，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑8.8mg，收率5％。Comparative Example 1-1. Ferrous sulfate heptahydrate was used instead of palladium acetate, and the molar weight was changed to 0.5 mmol, and the rest were the same as in Example 1. 8.8 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 5%.
对比例1-2、用四水合氯化钴代替醋酸钯，摩尔量改成0.5mmol，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑38.8mg，收率22％。Comparative example 1-2, replace palladium acetate with cobalt chloride tetrahydrate, change the molar weight into 0.5 mmol, and the rest are the same as in Example 1. 38.8 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 22%.
对比例1-3、用七水合硫酸亚铁代替醋酸钯，摩尔量不变，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑5.3mg，收率3％。Comparative example 1-3, replace palladium acetate with ferrous sulfate heptahydrate, the molar weight is constant, all the other are the same as embodiment 1. 5.3 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 3%.
对比例1-4、用四水合氯化钴代替醋酸钯，摩尔量不变，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑24.7mg，收率14％。Comparative example 1-4, replace palladium acetate with cobalt chloride tetrahydrate, the molar weight is constant, all the other are the same as embodiment 1. 24.7 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 14%.
对比例1-5、用醋酸镍代替醋酸钯，摩尔量不变，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑17.6mg，收率10％。Comparative example 1-5, replace palladium acetate with nickel acetate, molar weight is constant, all the other are the same as embodiment 1. 17.6 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 10%.
对比例1-6、用氯化钯代替醋酸钯，摩尔量不变，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑140.8mg，收率80％。Comparative example 1-6, replace palladium acetate with palladium chloride, molar weight is constant, all the other are the same as embodiment 1. 140.8 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 80%.
对比例1-7、将醋酸钯由0.05mmol改成0.1mmol，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑158.6mg，收率90％。Comparative Example 1-7, change palladium acetate from 0.05mmol to 0.1mmol, and the rest are the same as in Example 1. 158.6 mg of the product 4-phenyl-2-aminothiazole was obtained as a light yellow solid, with a yield of 90%.
对比例1-8、将醋酸钯由0.05mmol改成0.03mmol，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑82.8mg，收率47％。Comparative Example 1-8, change palladium acetate from 0.05mmol to 0.03mmol, and the rest are the same as in Example 1. 82.8 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 47%.
对比例1-9、用甲苯代替正丙醇，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑0mg，收率0％。Comparative example 1-9, replace n-propanol with toluene, all the other are the same as embodiment 1. 0 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, and the yield was 0%.
对比例1-10、用1,4-二氧六环代替正丙醇，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑105.7mg，收率60％。Comparative examples 1-10, using 1,4-dioxane instead of n-propanol, the rest are the same as in Example 1. 105.7 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 60%.
对比例1-11、用异丙醇代替正丙醇，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑144.5mg，收率82％。Comparative example 1-11, replace n-propanol with isopropanol, all the other are the same as embodiment 1. 144.5 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 82%.
对比例1-12、用丁醇代替正丙醇，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑141.0mg，收率80％。Comparative example 1-12, replace n-propanol with butanol, all the other are the same as embodiment 1. 141.0 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 80%.
对比例1-13、用乙醇代替正丙醇，反应温度为回流，其余同实施例1。得到淡黄色固体状产物4-苯基-2-氨基噻唑149.8mg，收率85％。Comparative example 1-13, replace n-propanol with ethanol, the reaction temperature is reflux, all the other are the same as embodiment 1. 149.8 mg of the product 4-phenyl-2-aminothiazole was obtained as a pale yellow solid, with a yield of 85%.
实施例2、 4-(2-溴苯基)-2-氨基噻唑(m2)Embodiment 2, 4-(2-bromophenyl)-2-aminothiazole (m2)
以1-(1-叠氮乙烯基)-2-溴苯代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到淡黄色固体状产物4-(2-溴苯基)-2-氨基噻唑227.1mg，收率89％。1-(1-azidovinyl)-2-bromobenzene is used to replace 1-azidostyrene, the molar weight is unchanged, and the rest is the same as in Example 1. 227.1 mg of the product 4-(2-bromophenyl)-2-aminothiazole was obtained as a pale yellow solid, with a yield of 89%.
其结构式为：Its structural formula is:
Pale yellow solid；mp:122.5-123.0℃；1H NMR(500MHz,CDCl3)δ7.70(d,J＝7.76,1H),7.63(d,J＝7.99,1H),7.33(t,J＝7.55,1H),7.16(t,J＝7.69,1H),6.95(s,1H),5.06(s,2H)；13C NMR(125MHz,CDCl3)δ166.64,149.11,135.72,133.75,131.54,129.15,127.46,121.79,107.81；HRMS(ESI):m/z calcd for C9H7BrN2S[M+H]+:254.9592,found:254.9594。Pale yellow solid; mp: 122.5-123.0℃; 1 H NMR (500MHz, CDCl 3 ) δ7.70(d, J=7.76,1H), 7.63(d, J=7.99,1H), 7.33(t, J= 7.55,1H),7.16(t,J=7.69,1H),6.95(s,1H),5.06(s,2H); 13 C NMR(125MHz,CDCl 3 )δ166.64,149.11,135.72,133.75,131.54,129.15 , 127.46, 121.79, 107.81; HRMS (ESI): m/z calcd for C 9 H 7 BrN 2 S[M+H] + : 254.9592, found: 254.9594.
实施例3、 4-(3-溴苯基)-2-氨基噻唑(m3)Embodiment 3, 4-(3-bromophenyl)-2-aminothiazole (m3)
以1-(1-叠氮乙烯基)-3-溴苯代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到淡黄色固体状产物4-(3-溴苯基)-2-氨基噻唑239.8mg，收率94％。1-(1-azidovinyl)-3-bromobenzene was used to replace 1-azidostyrene, the molar weight was unchanged, and the rest were the same as in Example 1. 239.8 mg of the product 4-(3-bromophenyl)-2-aminothiazole was obtained as a pale yellow solid, with a yield of 94%.
其结构式为：Its structural formula is:
Pale yellow solid；mp:129.7-131.5℃；1H NMR(500MHz,CDCl3)δ7.93(t,J＝1.61,1H),7.68(d,J＝7.81,1H),7.41(d,J＝7.93,1H),7.24(t,J＝7.88,1H),6.74(s,1H),5.18(s,2H)；13C NMR(125MHz,CDCl3)δ167.56,149.84.136.72,130.71,130.24,129.18,124.58,122.91,104.01；HRMS(ESI):m/z calcd for C9H7BrN2S[M+H]+:254.9592,found:254.9593。Pale yellow solid; mp: 129.7-131.5℃; 1 H NMR (500MHz, CDCl 3 ) δ7.93(t, J＝1.61, 1H), 7.68(d, J＝7.81, 1H), 7.41(d, J＝ 7.93,1H),7.24(t,J=7.88,1H),6.74(s,1H),5.18(s,2H); 13 C NMR(125MHz,CDCl 3 )δ167.56,149.84.136.72,130.71,130.24,129.18 , 124.58, 122.91, 104.01; HRMS (ESI): m/z calcd for C 9 H 7 BrN 2 S[M+H] + : 254.9592, found: 254.9593.
实施例4、 4-(4-溴苯基)-2-氨基噻唑(m4)Embodiment 4, 4-(4-bromophenyl)-2-aminothiazole (m4)
以1-(1-叠氮乙烯基)-4-溴苯代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到棕色固体状产物4-(4-溴苯基)-2-氨基噻唑219.4mg，收率86％。1-(1-azidovinyl)-4-bromobenzene was used to replace 1-azidostyrene, the molar weight was unchanged, and the rest were the same as in Example 1. 219.4 mg of the product 4-(4-bromophenyl)-2-aminothiazole was obtained as a brown solid, with a yield of 86%.
其结构式为：Its structural formula is:
Brown solid；mp:181.3-181.7℃；1H NMR(500MHz,CDCl3)δ7.65(d,J＝8.10,2H),7.49(d,J＝8.06,2H),6.73(s,1H),5.02(s,2H)；13C NMR(125MHz,CDCl3)δ167.38,150.32,133.66,131.82,127.68,121.74,103.52；HRMS(ESI):m/z calcd for C9H7BrN2S[M+H]+:254.9592,found:254.9596。Brown solid; mp: 181.3-181.7℃; 1 H NMR (500MHz, CDCl 3 ) δ7.65(d, J＝8.10, 2H), 7.49(d, J＝8.06, 2H), 6.73(s, 1H), 5.02(s,2H); 13 C NMR(125MHz,CDCl 3 )δ167.38,150.32,133.66,131.82,127.68,121.74,103.52; HRMS(ESI):m/z calcd for C 9 H 7 BrN 2 S[M+ H] + :254.9592, found: 254.9596.
实施例5、 4-(4-甲基苯基)-2-氨基噻唑(m5)Embodiment 5, 4-(4-methylphenyl)-2-aminothiazole (m5)
以1-(1-叠氮乙烯基)-4-甲苯代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到淡黄色固体状产物4-(4-甲基苯基)-2-氨基噻唑156.0mg，收率82％。1-(1-azidovinyl)-4-toluene was used to replace 1-azidostyrene, the molar weight was unchanged, and the rest were the same as in Example 1. 156.0 mg of the product 4-(4-methylphenyl)-2-aminothiazole was obtained as a pale yellow solid, with a yield of 82%.
其结构式为：Its structural formula is:
Pale yellow solid；mp:132.5-133.1℃；1H NMR(500MHz,CDCl3)δ7.66(d,J＝8.03Hz,2H),7.19(d,J＝7.92Hz,2H),6.65(s,1H),5.30(s,2H),2.36(s,3H)；13C NMR(125MHz,CDCl3)δ167.57,151.43,137.64,132.09,129.40,126.00,102.05,21.37；HRMS(ESI):m/z calcd forC10H10N2S[M+H]+:191.0643,found:191.0641。Pale yellow solid; mp: 132.5-133.1℃; 1 H NMR (500MHz, CDCl 3 ) δ7.66(d, J＝8.03Hz, 2H), 7.19(d, J＝7.92Hz, 2H), 6.65(s, 1H), 5.30(s, 2H), 2.36(s, 3H); 13 C NMR (125MHz, CDCl 3 ) δ167.57, 151.43, 137.64, 132.09, 129.40, 126.00, 102.05, 21.37; HRMS (ESI): m/z calcd for C 10 H 10 N 2 S[M+H] + :191.0643,found:191.0641.
实施例6、 4-(4-乙氧基-3-溴苯基)-2-氨基噻唑(m6)Embodiment 6, 4-(4-ethoxy-3-bromophenyl)-2-aminothiazole (m6)
以1-(1-叠氮乙烯基)-4-乙氧基-3-溴苯代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到白色固体状产物4-(4-乙氧基-3-溴苯基)-2-氨基噻唑266.3mg，收率89％。1-(1-azidovinyl)-4-ethoxy-3-bromobenzene was used instead of 1-azidostyrene, the molar weight was unchanged, and the rest were the same as in Example 1. 266.3 mg of the product 4-(4-ethoxy-3-bromophenyl)-2-aminothiazole was obtained as a white solid, with a yield of 89%.
其结构式为：Its structural formula is:
White solid；mp:176.8-177.4℃；1H NMR(500MHz,CDCl3)δ7.97(d,J＝2.11,1H),7.65(dd,J＝8.54,2.12,1H),6.88(d,J＝8.57,1H),6.60(s,1H),5.02(s,2H),4.12(q,J＝6.97,2H),1.48(t,J＝6.97,3H)；13C NMR(125MHz,DMSO)δ167.35,155.07,149.85,131.11,128.92,126.18,113.17,112.47,102.07,65.05,14.85；HRMS(ESI):m/z calcd for C11H11BrN2OS[M+H]+:298.9854,found:298.9855。White solid; mp: 176.8-177.4℃; 1 H NMR (500MHz, CDCl 3 ) δ7.97(d, J＝2.11, 1H), 7.65(dd, J＝8.54, 2.12, 1H), 6.88(d, J =8.57,1H),6.60(s,1H),5.02(s,2H),4.12(q,J=6.97,2H),1.48(t,J=6.97,3H); 13 C NMR(125MHz,DMSO) δ167.35,155.07,149.85,131.11,128.92,126.18,113.17,112.47,102.07,65.05,14.85; HRMS(ESI):m/z calcd for C 11 H 11 BrN 2 OS[M+H] + :298.9854,found 298.9855.
实施例7、 4-(3-硝基苯基)-2-氨基噻唑(m7)Embodiment 7, 4-(3-nitrophenyl)-2-aminothiazole (m7)
以1-(1-叠氮乙烯基)-3-硝基苯代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到淡黄色固体状产物4-(3-硝基苯基)-2-氨基噻唑143.8mg，收率65％。1-(1-azidovinyl)-3-nitrobenzene was used to replace 1-azidostyrene, the molar weight was unchanged, and the rest were the same as in Example 1. 143.8 mg of the product 4-(3-nitrophenyl)-2-aminothiazole was obtained as a pale yellow solid, with a yield of 65%.
其结构式为：Its structural formula is:
Pale yellow solid；mp:187.8-188.4℃；1H NMR(500MHz,d6-DMSO)δ8.61(s,1H),8.23(d,J＝4.54,1H),8.10(d,J＝5.14,1H),7.66(t,J＝8.41,1H),7.34(s,1H),7.23(s,2H)；13C NMR(125MHz,d6-DMSO)δ168.61,148.23,147.39,136.39,131.51,130.05,121.66,119.94,104.25；HRMS(ESI):m/z calcd for C9H7N3O2S[M+H]+:222.0337,found:222.0334。Pale yellow solid; mp:187.8-188.4℃; 1 H NMR (500MHz,d 6 -DMSO)δ8.61(s,1H),8.23(d,J=4.54,1H),8.10(d,J=5.14, 1H), 7.66(t, J=8.41, 1H), 7.34(s, 1H), 7.23(s, 2H); 13 C NMR (125MHz, d 6 -DMSO) δ168.61, 148.23, 147.39, 136.39, 131.51, 130.05 , 121.66, 119.94, 104.25; HRMS (ESI): m/z calcd for C 9 H 7 N 3 O 2 S[M+H] + : 222.0337, found: 222.0334.
实施例8、 4-(4-甲氧酰基苯基)-2-氨基噻唑(m8)Embodiment 8, 4-(4-methoxyacylphenyl)-2-aminothiazole (m8)
以4-(1-叠氮乙烯基)-苯甲酸甲酯代替1-叠氮苯乙烯，摩尔量不变，其余同实施例1。得到淡黄色固体状产物4-(4-甲氧酰基苯基)-2-氨基噻唑133.5mg，收率57％。Replace 1-azidostyrene with 4-(1-azidovinyl)-methyl benzoate, the molar weight is constant, and the rest are the same as in Example 1. 133.5 mg of the product 4-(4-methoxyacylphenyl)-2-aminothiazole was obtained as a pale yellow solid, with a yield of 57%.
其结构式为：Its structural formula is:
Pale yellow solid；mp:216.7-217.8℃；1H NMR(500MHz,d6-DMSO)δ7.96-7.92(m,4H),7.24(s,1H),7.15(s,2H),3.85(s,3H)；13C NMR(125MHz,d6-DMSO)δ168.41,166.07,148.74,139.17,129.55,127.87,125.61,104.52,52.06；HRMS(ESI):m/z calcd for C11H10N2O2S[M+H]+:235.0541,found:235.0541。Pale yellow solid; mp:216.7-217.8℃; 1 H NMR (500MHz,d 6 -DMSO)δ7.96-7.92(m,4H),7.24(s,1H),7.15(s,2H),3.85(s ,3H); 13 C NMR (125MHz, d 6 -DMSO) δ168.41, 166.07, 148.74, 139.17, 129.55, 127.87, 125.61, 104.52, 52.06; HRMS (ESI): m/z calcd for C 11 H 10 N 2 O 2 S[M+H] + :235.0541, found: 235.0541.
实施例9、 4-(1-萘基)-2-氨基噻唑(m9)Embodiment 9, 4-(1-naphthyl)-2-aminothiazole (m9)
以1-(1-叠氮乙烯基)萘代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到淡黄色固体状产物4-(1-萘基)-2-氨基噻唑95.0mg，收率42％。1-(1-azidovinyl)naphthalene is used to replace 1-azidostyrene, the molar weight is unchanged, and the rest are equal to Example 1. 95.0 mg of the product 4-(1-naphthyl)-2-aminothiazole was obtained as a light yellow solid, with a yield of 42%.
其结构式为：Its structural formula is:
Pale yellow solid；mp:161.3-161.8℃；1H NMR(500MHz,d6-DMSO)δ8.46-8.44(m,1H),7.95-7.93(m,1H),7.89(d,J＝8.13,1H),7.63(d,J＝6.26,1H),7.53-7.49(m,3H),7.11(s,2H),6.77(s,1H)；13C NMR(125MHz,d6-DMSO)δ168.01,150.08,133.53,133.52,130.77,128.16,127.95,126.62,126.26,125.92,125.82,125.46,105.03；HRMS(ESI):m/z calcd for C13H10N2S[M+H]+:227.0643,found:227.0645。Pale yellow solid; mp:161.3-161.8℃; 1 H NMR (500MHz,d 6 -DMSO)δ8.46-8.44(m,1H),7.95-7.93(m,1H),7.89(d,J＝8.13, 1H), 7.63 (d, J=6.26, 1H), 7.53-7.49 (m, 3H), 7.11 (s, 2H), 6.77 (s, 1H); 13 C NMR (125MHz, d 6 -DMSO) δ168. 01,150.08,133.53,133.52,130.77,128.16,127.95,126.62,126.26,125.92,125.82,125.46,105.03; HRMS(ESI):m/z calcd for C 13 H 10 N 2 S[M+H] + 0:4327. found: 227.0645.
实施例10、 4-(苯氨基甲基)-2-氨基噻唑(m10)Embodiment 10, 4-(phenylaminomethyl)-2-aminothiazole (m10)
以N-(2-叠氮烯丙基)苯胺代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到棕色固体状产物4-(苯氨基甲基)-2-氨基噻唑143.5mg，收率56％。N-(2-azidoallyl)aniline was used to replace 1-azidostyrene, the molar weight was unchanged, and the rest were the same as in Example 1. 143.5 mg of the product 4-(anilinomethyl)-2-aminothiazole was obtained as a brown solid, with a yield of 56%.
其结构式为：Its structural formula is:
Brown solid；mp:113.5-114.7℃；1H NMR(500MHz,d6-DMSO)δ7.04(t,J＝7.47,2H),6.86(s,2H),6.59(d,J＝7.75,2H),6.51(t,J＝7.02,1H),6.25(s,1H),5.88(s,1H),4.02(s,2H)；13C NMR(125MHz,d6-DMSO)δ168.44,150.28,148.65,128.75,115.70,112.20,101.26,43.56；HRMS(ESI):m/z calcd for C10H11N3S[M+H]+:206.0752,found:206.0749。Brown solid; mp: 113.5-114.7℃; 1 H NMR (500MHz, d 6 -DMSO) δ7.04(t, J=7.47, 2H), 6.86(s, 2H), 6.59(d, J=7.75, 2H ),6.51(t,J=7.02,1H),6.25(s,1H),5.88(s,1H),4.02(s,2H); 13 C NMR(125MHz,d 6 -DMSO)δ168.44,150.28,148.65 ,128.75,115.70,112.20,101.26,43.56; HRMS(ESI):m/z calcd for C 10 H 11 N 3 S[M+H] + :206.0752,found:206.0749.
实施例11、反式-4-(3-苯基烯丙基氧甲基)-2-氨基噻唑(m11)Example 11, trans-4-(3-phenylallyloxymethyl)-2-aminothiazole (m11)
以反式-[3-(2-叠氮烯丙氧基)丙烯基]苯代替1-叠氮苯乙烯，摩尔量不变，其余等同于实施例1。得到淡黄色油状物反式-4-(3-苯基烯丙基氧甲基)-2-氨基噻唑137.9mg，收率56％。Trans-[3-(2-azidoallyloxy)propenyl]benzene was used to replace 1-azidostyrene, the molar weight was unchanged, and the rest were the same as in Example 1. 137.9 mg of trans-4-(3-phenylallyloxymethyl)-2-aminothiazole was obtained as a light yellow oily substance, yield 56%.
其结构式为：Its structural formula is:
Pale yellow oil；1H NMR(500MHz,CDCl3)δ7.38(d,J＝7.26,2H),7.31(t,J＝7.55,2H),7.23(t,J＝7.28,1H),6.62(d,J＝15.93,1H),6.42(s,1H),6.32(dt,J＝6.14,15.94,1H),5.34(s,2H),4.42(s,2H)4.22(d,J＝6.10,2H)；13C NMR(125MHz,DMSO)δ168.64,149.21,136.69,132.83,128.60,127.75,126.56,125.91,105.60,71.09,67.84；HRMS(ESI):m/z calcd for C13H14N2OS[M+H]+:247.0905,found:247.0905。Pale yellow oil; 1 H NMR (500MHz, CDCl 3 ) δ7.38(d, J=7.26, 2H), 7.31(t, J=7.55, 2H), 7.23(t, J=7.28, 1H), 6.62( d,J=15.93,1H),6.42(s,1H),6.32(dt,J=6.14,15.94,1H),5.34(s,2H),4.42(s,2H)4.22(d,J=6.10, 2H); 13 C NMR (125MHz, DMSO) δ168.64, 149.21, 136.69, 132.83, 128.60, 127.75, 126.56, 125.91, 105.60, 71.09, 67.84; HRMS (ESI): m/z calcd for C 13 H 14 N 2 OS [M+H] + :247.0905, found: 247.0905.
最后，还需要注意的是，以上列举的仅是本发明的若干个具体实施例。显然，本发明不限于以上实施例，还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形，均应认为是本发明的保护范围。Finally, it should be noted that the above examples are only some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and many variations are possible. All deformations that can be directly derived or associated by those skilled in the art from the content disclosed in the present invention should be considered as the protection scope of the present invention.
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| CN107586282A (en) * | 2017-10-12 | 2018-01-16 | 兰州大学 | A kind of method of the visible optical drive synthesis aminothiazole of 4 alkyl or aryl 2 |
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