CN112778231A - 一种4-甲基噻唑-5-甲醛的新型合成方法 - Google Patents
一种4-甲基噻唑-5-甲醛的新型合成方法 Download PDFInfo
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- JJVIEMFQPALZOZ-UHFFFAOYSA-N 4-methyl-1,3-thiazole-5-carbaldehyde Chemical compound CC=1N=CSC=1C=O JJVIEMFQPALZOZ-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 238000001308 synthesis method Methods 0.000 title claims abstract description 13
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical group O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims abstract description 21
- ZSPCITYHOYJDBW-UHFFFAOYSA-N (4-methyl-1,3-thiazol-5-yl)methanol Chemical compound CC=1N=CSC=1CO ZSPCITYHOYJDBW-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 230000003197 catalytic effect Effects 0.000 claims abstract description 16
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 12
- -1 piperidine nitroxide free radical Chemical class 0.000 claims abstract description 10
- 239000007800 oxidant agent Substances 0.000 claims abstract description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 230000001590 oxidative effect Effects 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 10
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 4
- 235000010288 sodium nitrite Nutrition 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 claims description 3
- 239000012414 tert-butyl nitrite Substances 0.000 claims description 3
- QQZWEECEMNQSTG-UHFFFAOYSA-N Ethyl nitrite Chemical compound CCON=O QQZWEECEMNQSTG-UHFFFAOYSA-N 0.000 claims description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 2
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 claims description 2
- 229910000360 iron(III) sulfate Inorganic materials 0.000 claims description 2
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 claims description 2
- BLLFVUPNHCTMSV-UHFFFAOYSA-N methyl nitrite Chemical compound CON=O BLLFVUPNHCTMSV-UHFFFAOYSA-N 0.000 claims description 2
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004304 potassium nitrite Substances 0.000 claims description 2
- 235000010289 potassium nitrite Nutrition 0.000 claims description 2
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 16
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 2
- 229910001882 dioxygen Inorganic materials 0.000 abstract description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- WKBQQWDVVHGWDB-UHFFFAOYSA-N 1,3-thiazol-5-ylmethanol Chemical compound OCC1=CN=CS1 WKBQQWDVVHGWDB-UHFFFAOYSA-N 0.000 description 1
- CSGAUKGQUCHWDP-UHFFFAOYSA-N 1-hydroxy-2,2,6,6-tetramethylpiperidin-4-ol Chemical compound CC1(C)CC(O)CC(C)(C)N1O CSGAUKGQUCHWDP-UHFFFAOYSA-N 0.000 description 1
- KRNWYBIEWUXCOB-UHFFFAOYSA-N 1-hydroxy-4-methoxy-2,2,6,6-tetramethylpiperidine Chemical compound COC1CC(C)(C)N(O)C(C)(C)C1 KRNWYBIEWUXCOB-UHFFFAOYSA-N 0.000 description 1
- RVWUHFFPEOKYLB-UHFFFAOYSA-N 2,2,6,6-tetramethyl-1-oxidopiperidin-1-ium Chemical compound CC1(C)CCCC(C)(C)[NH+]1[O-] RVWUHFFPEOKYLB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- AFZFFLVORLEPPO-UVYJNCLZSA-N cefditoren pivoxil Chemical compound S([C@@H]1[C@@H](C(N1C=1C(=O)OCOC(=O)C(C)(C)C)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1\C=C/C=1SC=NC=1C AFZFFLVORLEPPO-UVYJNCLZSA-N 0.000 description 1
- 229960002142 cefditoren pivoxil Drugs 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910000314 transition metal oxide Inorganic materials 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- 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
- C07D277/22—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
- B01J31/28—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24 of the platinum group metals, iron group metals or copper
- B01J31/30—Halides
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明提出了一种4‑甲基噻唑‑5‑甲醛的新型合成方法，包括如下步骤：以4‑甲基噻唑‑5‑甲醇为原料，进行催化氧化反应得到4‑甲基噻唑‑5‑甲醛；所述催化氧化反应中，氧化剂为分子氧(氧气或空气)，催化体系由催化剂A、催化剂B、催化剂C组成；催化剂A为哌啶类氮氧自由基及其衍生物，催化剂B为氮氧化物及其等价物，催化剂C为质子酸、溴化物或三价铁盐。本发明所述反应原料绿色、廉价，催化体系高效、环保，整个反应过程清洁、安全，从经济或环保角度考虑都极具优势。
Description
技术领域
本发明涉及医药中间体合成技术领域，具体涉及一种4-甲基噻唑-5甲醛的新型合成方法。
背景技术
4-甲基噻唑-5-甲醛是制备第三代头孢类抗菌药物头孢妥仑匹酯片的一个重要中间体，其化学结构为
实际生产中，以4-甲基噻唑-5-甲醇为起始原料合成4-甲基噻唑-5-甲醛时，多使用价格昂贵且有毒的氧化剂，如铬试剂、锰试剂及其他过渡金属氧化物、高价碘试剂等，且氧化剂的用量大多过量，从而产生大量废弃污染物，对环保造成了巨大的压力。
目前，2,2,6,6-四甲基哌啶-氮-氧自由基(TEMPO)及其衍生物在醇氧化反应中表现出了突出的选择性和催化活性。TEMPO作为有机小分子可避免有毒金属离子对环境造成的污染，并且反应条件温和、好回收，在实际生产中有着广泛应用。
专利CN1628108A中公开了由4-甲基噻唑-5-甲醇制备4-甲基噻唑-5-甲醛的两种方法。一种使用的是TEMPO/KBr/NaClO氧化体系，另一种使用氯铬酸吡啶嗡盐(PCC)做氧化剂。前一种方法收率较高，但是次氯酸钠要在低温下使用,条件较苛刻；后一种方法产品纯度较高，但收率不高，重金属氧化剂的使用也导致固废量增加、环境污染及产品质量不稳定等缺点。
专利CN103030604A中使用TEMPO做催化剂，次氯酸钙或次溴酸钠为氧化剂的方法将4-甲基噻唑-5-甲醇氧化得到4-甲基噻唑-5-甲醛，虽然不需要使用溴化钾一类的助催化剂，但是反应收率不高。
发明内容
基于背景技术存在的问题，本发明提供了一种以4-甲基噻唑-5-甲醇为原料，绿色、高效、经济的4-甲基噻唑-5-甲醛的合成方法。
本发明是通过如下技术方案实现的：
以4-甲基噻唑-5-甲醇为原料，一步催化氧化制备得到4-甲基噻唑-5-甲醛；所述催化氧化反应中，氧化剂为分子氧(氧气或空气)，催化体系由催化剂A、催化剂B、催化剂C组成；催化剂A为哌啶类氮氧自由基及其衍生物，催化剂B为氮氧化物及其等价物，催化剂C为质子酸、溴化物或三价铁盐。
其中，所述哌啶类氮氧自由基及其衍生物为以下结构化合物中一种或多种的组合：
所述氮氧化物及其等价物为亚硝酸钠、亚硝酸钾、亚硝酸甲酯、亚硝酸乙酯、亚硝酸叔丁酯、亚硝酸异戊酯中一种或多种的组合。
所述质子酸为盐酸。溴化物为溴化氢、溴化钠、溴化钾中一种或多种的组合。三价铁盐为氯化铁、溴化铁、硫酸铁、硝酸铁、铁氰化钾中一种或多种的组合。
其中，所述催化氧化反应的溶剂为二氯甲烷、氯仿、1,2-二氯乙烷、氯苯、氟苯、三氟甲苯、乙腈、乙酸中一种或多种的组合。
其中，所述催化氧化反应的温度为0-120℃，优选为20-80℃。
其中，所述哌啶类氮氧自由基的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述氮氧化物及其等价物的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述质子酸的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述溴化物的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述三价铁盐的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％。
本发明的原料和试剂均市售可得。
本发明的有益效果为：
本发明所述反应原料绿色、廉价，所述催化体系高效、环保，整个反应过程清洁、安全，无论从经济还是环保角度考虑都极具优势。
附图说明
图1本发明提出的4-甲基噻唑-5-甲醛的合成路线
图2本发明制备得到的4-甲基噻唑-5-甲醛核磁氢谱图
具体实施方式
为了使本领域技术人员更好地理解本发明技术方案，下面结合具体实施例对本发明技术方案作进一步详细说明。
实施例1
1L三口瓶内依次加入4-甲基噻唑-5-甲醇129.2g(1.0mol)、4-羟基-2,2,6,6-四甲基哌啶氧化物3.44g(0.02mol)、三氯化铁8.1g(0.05mol)、亚硝酸钠3.5g(0.05mol)和1,2-二氯乙烷400mL，室温常压条件下，空气中搅拌反应8小时。
取样，检测至反应终点；将反应液转移至分液漏斗中，用饱和硫代硫酸钠溶液洗涤二次，分液后有机相用无水硫酸钠干燥过夜，减压蒸馏回收溶剂，得到淡黄色固体，再用正庚烷重结晶，得到淡黄色晶体粉末状4-甲基噻唑-5-甲醛，含量99％，收率83％。
实施例2
将4-甲基噻唑-5-甲醇129.2g(1mol)、2,2,6,6-四甲基哌啶氧化物5.4g(0.03mol)、30％盐酸12g(0.1mol)、亚硝酸钠3.5g(0.05mol)投入1L三口瓶中，加入二氯甲烷400mL，搅拌均匀后通入空气，常温下反应10小时。
反应结束，将反应液转移至分液漏斗中，用饱和碳酸氢钠溶液洗涤两次,分液后有机相用无水硫酸钠干燥过夜，减压蒸馏回收溶剂，得到淡黄色固体，再用正庚烷重结晶，得到淡黄色晶体粉末状4-甲基噻唑-5-甲醛含量99％，收率96％。
实施例3
将4-甲基噻唑-5-甲醇129.2g(1mol)、4-甲氧基-2,2,6,6-四甲基哌啶氧化物18.6g(0.1mol)、溴化钾11.9g(0.1mol)、亚硝酸叔丁酯10.3g(0.1mol)投入1L压力釜中，加入二氯甲烷400mL，搅拌均匀后通入氧气，升温至80℃，回流反应6小时。
反应结束，冷却至室温，小心卸去压力,将反应液转移至分液漏斗中，分液后有机相用无水硫酸钠干燥过夜，减压蒸馏回收溶剂，得到淡黄色固体，再用正庚烷重结晶，得到淡黄色晶体粉末状4-甲基噻唑-5-甲醛含量99％，收率91％。
以上所述，仅为本发明较佳的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，根据本发明的技术方案及其发明构思加以等同替换或改变，都应涵盖在本发明的保护范围之内。
Claims (9)
1.一种4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述方法包括以下步骤：以4-甲基噻唑-5-甲醇为原料，进行催化氧化反应得到4-甲基噻唑-5-甲醛；所述催化氧化反应中，氧化剂为氧气或空气，催化体系由催化剂A、催化剂B、催化剂C组成；催化剂A为哌啶类氮氧自由基及其衍生物，催化剂B为氮氧化物及其等价物，催化剂C为质子酸、溴化物或三价铁盐。
2.根据权利要求1所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述哌啶类氮氧自由基及其衍生物为以下结构的化合物中一种或多种的组合：
3.根据权利要求1或2所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述氮氧化物及其等价物为亚硝酸钠、亚硝酸钾、亚硝酸甲酯、亚硝酸乙酯、亚硝酸叔丁酯、亚硝酸异戊酯中一种或多种的组合。
4.根据权利要求1-3任一项所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述质子酸为盐酸。
5.根据权利要求1-4任一项所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述溴化物为溴化氢、溴化钠、溴化钾中一种或多种的组合。
6.根据权利要求1-5任一项所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述三价铁盐为氯化铁、溴化铁、硫酸铁、硝酸铁、铁氰化钾中一种或多种的组合。
7.根据权利要求1-6任一项所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述催化氧化反应的溶剂为二氯甲烷、氯仿、1,2-二氯乙烷、氯苯、氟苯、三氟甲苯、乙腈、乙酸中一种或多种的组合。
8.根据权利要求1-7任一项所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述催化氧化反应的温度为0-120℃。
9.根据权利要求1-8任一项所述4-甲基噻唑-5-甲醛的新型合成方法，其特征在于，所述哌啶类氮氧自由基的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述氮氧化物及其等价物的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述质子酸的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述溴化物的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％；所述三价铁盐的用量为4-甲基噻唑-5-甲醇摩尔量的0.1-20％。
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