CN115124413B - 一种羟基香茅醇制备羟基香茅醛的方法 - Google Patents
一种羟基香茅醇制备羟基香茅醛的方法 Download PDFInfo
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- CN115124413B CN115124413B CN202210152167.4A CN202210152167A CN115124413B CN 115124413 B CN115124413 B CN 115124413B CN 202210152167 A CN202210152167 A CN 202210152167A CN 115124413 B CN115124413 B CN 115124413B
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- hydroxycitronellol
- hydroxycitronellal
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- FPCCDPXRNNVUOM-UHFFFAOYSA-N Hydroxycitronellol Chemical compound OCCC(C)CCCC(C)(C)O FPCCDPXRNNVUOM-UHFFFAOYSA-N 0.000 title claims abstract description 62
- WPFVBOQKRVRMJB-UHFFFAOYSA-N hydroxycitronellal Chemical compound O=CCC(C)CCCC(C)(C)O WPFVBOQKRVRMJB-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims abstract description 31
- 239000003054 catalyst Substances 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- 239000003446 ligand Substances 0.000 claims abstract description 33
- 229910052751 metal Inorganic materials 0.000 claims abstract description 30
- 239000002184 metal Substances 0.000 claims abstract description 30
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 239000007789 gas Substances 0.000 claims abstract description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000001301 oxygen Substances 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 230000009471 action Effects 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 239000000047 product Substances 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- QMVPMAAFGQKVCJ-UHFFFAOYSA-N citronellol Chemical compound OCCC(C)CCC=C(C)C QMVPMAAFGQKVCJ-UHFFFAOYSA-N 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000005265 energy consumption Methods 0.000 description 5
- QMVPMAAFGQKVCJ-SNVBAGLBSA-N (R)-(+)-citronellol Natural products OCC[C@H](C)CCC=C(C)C QMVPMAAFGQKVCJ-SNVBAGLBSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JGQFVRIQXUFPAH-UHFFFAOYSA-N beta-citronellol Natural products OCCC(C)CCCC(C)=C JGQFVRIQXUFPAH-UHFFFAOYSA-N 0.000 description 4
- 235000000484 citronellol Nutrition 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000010949 copper Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000000686 essence Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000234435 Lilium Species 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- -1 hydroxyl citronellol Chemical compound 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000012465 retentate Substances 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 239000005751 Copper oxide Substances 0.000 description 1
- 241000080590 Niso Species 0.000 description 1
- 244000223014 Syzygium aromaticum Species 0.000 description 1
- 235000016639 Syzygium aromaticum Nutrition 0.000 description 1
- IOPQYDKQISFMJI-UHFFFAOYSA-N [1-[2-bis(4-methylphenyl)phosphanylnaphthalen-1-yl]naphthalen-2-yl]-bis(4-methylphenyl)phosphane Chemical compound C1=CC(C)=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC(C)=CC=1)C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 IOPQYDKQISFMJI-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- CXQRZKIIGJLWPJ-UHFFFAOYSA-N diphenylphosphane;1-naphthalen-1-ylnaphthalene Chemical group C=1C=CC=CC=1PC1=CC=CC=C1.C1=CC=C2C(C=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 CXQRZKIIGJLWPJ-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004134 energy conservation Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 238000005839 oxidative dehydrogenation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/37—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups
- C07C45/38—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups being a primary hydroxyl group
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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
- B01J31/2452—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
- B01J31/2452—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom
- B01J31/2457—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom comprising aliphatic or saturated rings, e.g. Xantphos
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- B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
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Abstract
本发明公开了一种羟基香茅醇制备羟基香茅醛的方法,包括:在金属配体催化剂的作用下,羟基香茅醇和含氧气体进行氧化反应,反应结束后得到所述羟基香茅醛。该制备方法采用了新的催化剂,有效地提高了反应的转化率和选择性,并且反应结束之后,后处理简单,催化剂能够方便地进行套用。
Description
技术领域
本发明属于精细化工技术领域,具体涉及一种羟基香茅醇制备羟基香茅醛的方法。
背景技术
羟基香茅醛,化学名称为3,7-二甲基-7-羟基辛醛,纯品为较粘稠的无色液体,具有细腻愉快的铃兰和百合似的花香香气,清甜有力,广泛应用于日化香精,常用作香料,配制丁香、百合等花香型香精,用于化妆品;也用作食用香料的稳定剂,配制柠檬、樱桃、柑橘等食用香精,并可起到调和作用,是一种重要的大宗香料。
羟基香茅醛的主要合成方法之一为:以香茅醇为原料,依次经过水合、氧化脱氢得到产品。
专利US3940446A公开以香茅醇为起始原料,先经端位双键水合生成羟基香茅醇,再以自制的氧化铜为催化剂,在280℃、15kPa真空下反应得到羟基香茅醛,转化率为55.6%,选择性为88.5%,催化剂仅能连续套用16次。该方法的反应条件苛刻,催化剂容易失活,且存在转化率低,高温下羟基香茅醛因聚合而发生变质等缺点,严重影响反应的收率和后期的产品质量,能耗浪费严重,不符合节能降耗的要求,限制了该方法的工业普及性。
专利CN112473704A公开在固定床中,以羟基香茅醇为原料,蜂窝双金属陶瓷为催化剂,在150~180℃,控制体系绝对压力0.95bar~1.05bar,汽化的羟基香茅醇和氧气、氮气混合后进入固定床,进行脱氢-氧化反应得到羟基香茅醛。该方法使用的催化剂虽然能高收率、高选择性的获得羟基香茅醛,但是该催化剂的成分及制备过程较为复杂,且使用价格昂贵的钯、铂、钌、铑作为活性成分,不利于其在工业上的大规模推广和使用。
专利CN111068668A公开以羟基香茅醇为原料,负载型双金属为催化剂,在80~150℃下,反应压力0.1~2MPa,在固定床、滴流床或反应釜等反应器中反应,生成羟基香茅醛。该方法使用的催化剂的活性成分为贵金属钯、金、铂、铱、铑、钌和锇,价格昂贵,导致生产成本较高,不利于羟基香茅醛的工业化大生产。
专利CN113666809A公开了以羟基香茅醇为原料,以羟基香茅醇为原料,采用2,2,6,6-四甲基哌啶氧化物(TEMPO)/NaClO催化氧化体系合成羟基香茅醛。该方法的催化体系中的二氯乙烷具有致癌性,对羟基香茅醛使用的安全性存在潜在影响。另外,该方法在后处理时,使用5%亚硫酸钠和5%碳酸氢钠洗涤油相,会产生废盐和废水,不符合清洁生产的环保理念。
专利CN113666810A公开以羟基香茅醇为原料,基于Fe(NO3)3/4-OH-TEMPO催化体系,30~70℃,催化分子氧化羟基香茅醇合成羟基香茅醛。该方法的催化剂为Fe(NO3)3/4-OH-TEMPO,难以回收,无法实现催化剂的循环套用,不仅增加了生产成本,对环境也存在潜在威胁。另外,该方法的产率最高为71.6%,有待提升。
综上,现有技术中,羟基香茅醇氧化生成羟基香茅醛的反应中,均存在明显的缺陷,如转化率低,副反应多,收率不佳,能耗浪费等。因此迫切需要开发一种环保高效经济的羟基香茅醇氧化脱氢合成羟基香茅醛的工艺,以满足工业化大生产的需求。
发明内容
本发明提供了一种羟基香茅醇制备羟基香茅醛的方法,该羟基香茅醛的制备方法中采用了新的催化剂,在温和的反应条件下,高转化率、高选择性的得到了羟基香茅醛,很好的解决现有技术中存在的转化率低、选择性低、能耗高的技术问题,具有较好的工业化应用前景。
为了实现上述发明目的,本发明的技术方案如下:
一种羟基香茅醇制备羟基香茅醛的方法,包括:在金属配体催化剂的作用下,羟基香茅醇和含氧气体进行氧化反应,反应结束后得到所述羟基香茅醛粗品;粗品经精馏得到所述羟基香茅醛成品。
所述的金属配体催化剂包含活性金属和膦配体;
所述膦配体的结构式如下:
R1、R2、R3、R4独立地选自环己基、取代或者未取代的苯基,所述苯基上的取代基选自C1~C6烃基、C1~C4烷氧基、卤素中的一个、两个或者多个;
所述活性金属含有Fe、Co、Mn、Cu、Ni、Sn、Pb、Zn元素中的一种、两种或者多种。
本发明中,采用新的催化剂催化制备羟基香茅醛,有效地提高了反应的转化率和选择性,并且反应结束之后,后处理简单,催化剂能够方便地进行套用。
作为优选,所述金属配体催化剂,采用以下方法制备得到:
(1)将金属盐或其水合物和溶剂混合后搅拌至完全溶解,得到体系1;
(2)将配体和甲醇混合后搅拌至无浑浊,得到体系2;
(3)在50~80℃条件下,将体系2滴加到体系1中进行反应,反应结束之后,经过后处理得到所述的金属配体催化剂,其中,所述后处理包括浓缩、过滤、洗涤、烘干等步骤。
作为优选,所述的R1、R2、R3、R4可以相同,也可以不同,独立地选自Ph-,4-CH3C6H4-(配体记为p-Tol-BINAP),4-CH3OC6H4-(配体记为p-MeO-BINAP),3-CH3C6H4-(配体记为m-Tol-BINAP),3,5-(CH3)2C6H4-(配体记为3,5-Xylyl-BINAP),3,5-(tBu)2C6H3-(配体记为3,5-(tBu)2-BINAP),4-FC6H4-(配体记为4-F-BINAP),4-ClC6H4-(配体记为4-Cl-BINAP),-环己基(配体记为Cy-BINAP)中的一种、两种或者多种。
作为优选,在所述金属配体催化剂的制备步骤中,所述金属盐为硝酸盐、氯盐、硫酸盐、醋酸盐、乙酰丙酮盐、碱式碳酸盐中的一种、两种或者多种;作为进一步的优选,所述的金属盐为Fe(NO3)2、FeSO4、Fe(OAc)2、FeCl2、Ni(NO3)2、NiSO4、NiCl2、Ni(OAc)2、Ni(acac)2、ZnSO4、ZnCl2、Zn(NO3)2、Zn(OAc)2、CuSO4、Cu(OAc)2、Cu(NO3)2、Cu2(OH)2CO3、Mn(NO3)2、MnSO4、Mn(NO3)2、MnCl2、Co(NO3)2、CoSO4、CoCl2、Co(OAc)2、Pb(NO3)2、SnCl2或其水合物中的一种、两种或者多种。
作为优选,在所述金属配体催化剂的制备步骤中,所述金属盐和所述配体的摩尔比为1.0:1.0~1.5。
作为优选,在所述金属配体催化剂的制备步骤(1)和(2)中,溶剂独立地为水或有机溶剂,其中所述的有机溶剂为乙醇、甲醇、丙酮中的一种,其中催化剂制备步骤(1)和(2)的溶剂可以相同,也可以不同。
所述金属配体催化剂和所述羟基香茅醇的质量比为0.005~0.07:1.0。
作为优选,所述氧化反应温度为60~120℃,进一步优选为80~100℃。
作为优选,所述氧化反应的氧为分子氧,选自纯氧或空气;所述氧化反应为常压或微正压反应。
作为优选,所述氧化反应在无溶剂或有溶剂存在条件下均可进行。若使用有机溶剂,可根据反应工况进行选择,例如甲苯或二甲苯等。
本发明中,反应粗产物中未反应完全的羟基香茅醇以及溶剂,均可通过精馏分离回收利用,进一步提高原料羟基香茅醇和溶剂的利用率。
本发明所述的氧化反应的方法可以采用本领域公知的工艺进行,包括但不限于间歇釜式、固定床等本领域技术人员所熟知的工艺,本发明采用间歇釜式。
现有技术相比,本发明具有的有益效果体现在:
(1)本发明提供了一种用于连续或间歇生产羟基香茅醛的催化剂,利用该催化剂催化羟基香茅醇发生氧化反应制备羟基香茅醛,原料转化率高、产物收率高、催化剂选择性好,有效减少了副反应的发生。
(2)本发明中生产羟基香茅醛的方法反应条件温和,降低能耗,符合当下节能降耗的环保理念。
(3)本发明使用的催化剂价格低廉,可以替代现有技术中的贵金属,且取得了较好的催化效果,经济性好,节省了生产成本。
具体实施方式
催化剂制备实施例
实施例1
30℃下,将0.1mol的FeCl2·4H2O溶于100mL的乙醇中,搅拌之后完全溶解,得到体系1;35℃下,将0.1mol的2,2`-双(二苯基膦)-1,1`-联萘(BINAP)配体和100mL甲醇混合,搅拌至无浑浊,得到体系2;将体系1的温度升高至50℃,将体系2的溶液匀速滴加到体系1中,30min滴加完毕后,继续升温至60℃,保温反应6小时,降温至20℃将反应后体系常压浓缩至无液相流出,过滤,将过滤所得截留物用水淋洗,将淋洗后截留物真空烘干,得到催化剂BINAP-FeCl2,备用。
实施例2~44
按照实施例1的方法,改变添加的金属盐和配体的种类,分别得到如下催化剂(表1)。
表1实施例2~44对应的催化剂的及制备参数
羟基香茅醛的制备实施例
氧化反应在烧瓶中进行,按比例加入羟基香茅醇(174.29g)和催化剂,使用空气鼓泡,开启搅拌,常压下保温反应。反应结束后,使用气相色谱仪分析反应液,计算羟基香茅醇转化率以及羟基香茅醛选择性。然后,粗品经精馏得到羟基香茅醛成品,并通过气相色谱仪分析成品纯度。结果如下表2。
表2羟基香茅醛的制备
催化剂套用实施例
将实施例49的催化剂3,5-(tBu)2-BINAP-Fe(NO3)2进行循环套用制备羟基香茅醛,操作同实施例49,具体如下如下:
氧化反应在烧瓶中进行,按比例加入羟基香茅醇(174.29g)和催化剂,使用空气鼓泡,开启搅拌,常压下保温反应。反应结束后,使用气相色谱仪分析反应液,计算羟基香茅醇转化率以及羟基香茅醛选择性。然后,将过滤得到的催化剂和精馏回收的溶剂在相同条件下进行循环套用,结果如表3所示。
表3催化剂套用数据
催化剂套用十次后,反应的转化率下降了0.8%,选择性下降了0.3%,说明本发明的催化剂非常稳定,可以重复使用。
除特殊说明的外,本发明所述的百分数均为质量百分数,所述的比值均为质量比。
以上所述的具体实施方式对本发明的技术方案和有益效果进行了详细说明,应理解的是以上所述仅为本发明的最优选实施例,并不用于限制本发明,凡在本发明的原则范围内所做的任何修改、补充和等同替换等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种羟基香茅醇制备羟基香茅醛的方法,其特征在于,包括:在金属配体催化剂的作用下,羟基香茅醇和含氧气体进行氧化反应,反应结束后得到所述羟基香茅醛;
所述的金属配体催化剂包含活性金属和膦配体;
所述膦配体的结构式如下:
R1、R2、R3、R4独立地选自环己基、取代或者未取代的苯基,所述苯基上的取代基选自C1~C6烃基、C1~C4烷氧基、卤素中的一个、两个或者多个;
所述活性金属含有Fe、Co、Mn、Cu、Ni、Sn、Pb、Zn元素中的一种、两种或者多种。
2.根据权利要求1所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,所述的金属配体催化剂采用以下方法制备得到:
(1)将含有所述活性金属的金属盐和溶剂混合后搅拌至完全溶解,得到体系1;
(2)将膦配体和溶剂混合后搅拌至无浑浊,得到体系2;
(3)在50~80℃条件下,将体系2加入到体系1中进行反应,反应结束之后,经过后处理得到所述的金属配体催化剂。
3.根据权利要求1所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,所述的R1、R2、R3、R4可相同或不同,独立地选自Ph-,4-CH3C6H4-,4-CH3OC6H4-,3-CH3C6H4-,3,5-(CH3)2C6H4-,3,5-(tBu)2C6H3-,4-FC6H4-,4-ClC6H4-,环己基中的一种、两种或者多种。
4.根据权利要求2所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,所述金属盐为硝酸盐、氯盐、硫酸盐、醋酸盐、乙酰丙酮盐、碱式碳酸盐或其水合物中的一种、两种或者多种。
5.根据权利要求2所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,所述金属盐和所述配体的摩尔比为1.0:1.0~1.5。
6.根据权利要求2所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,在所述金属配体催化剂的制备步骤(1)和(2)中,溶剂独立地为水或有机溶剂,其中所述的有机溶剂为乙醇、甲醇、丙酮中的一种。
7.根据权利要求1~6任一项所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,所述的氧化反应在无溶剂或有溶剂存在条件下均可进行;
当有溶剂时,溶剂为甲苯或二甲苯。
8.根据权利要求1~6任一项所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,在所述的氧化反应中,所述的金属配体催化剂和所述羟基香茅醇的质量比为0.005~0.07:1.0。
9.根据权利要求1~6任一项所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,所述的氧化反应的温度为60~120℃。
10.根据权利要求1~6任一项所述的羟基香茅醇制备羟基香茅醛的方法,其特征在于,所述氧化反应在纯氧或空气中进行,反应压力为常压或微正压反应。
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0002498A1 (de) * | 1977-12-15 | 1979-06-27 | BASF Aktiengesellschaft | Verfahren zur Herstellung von Hydroxycitronellol |
US4347387A (en) * | 1980-12-04 | 1982-08-31 | Takasago Perfumery Co., Ltd. | Process for preparing hydroxycitronellal |
CN102503787A (zh) * | 2011-10-24 | 2012-06-20 | 合肥工业大学 | 一步法制备香茅醛的方法 |
WO2015070026A1 (en) * | 2013-11-11 | 2015-05-14 | Massachusetts Institute Of Technology | Nickel pre-catalysts and related compositions and methods |
CN110963902A (zh) * | 2019-12-05 | 2020-04-07 | 万华化学集团股份有限公司 | 一种水油两相不对称氢化合成r-香茅醛的方法及用于该方法的催化剂 |
CN110981707A (zh) * | 2019-12-19 | 2020-04-10 | 万华化学集团股份有限公司 | 一种橙花醇或香叶醇异构合成手性香茅醛的方法 |
CN112194686A (zh) * | 2020-10-29 | 2021-01-08 | 西安凯立新材料股份有限公司 | [(s)-(-)-2,2`-双(二苯基膦)-1,1`-联萘]二氯化铂的制备方法 |
CN112642489A (zh) * | 2020-12-23 | 2021-04-13 | 山东新和成药业有限公司 | 一种均相双金属络合催化剂、其制备方法及其在醇制备醛中的应用 |
CN114988990A (zh) * | 2022-06-15 | 2022-09-02 | 万华化学集团股份有限公司 | 一种香兰素的制备方法 |
-
2022
- 2022-02-18 CN CN202210152167.4A patent/CN115124413B/zh active Active
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0002498A1 (de) * | 1977-12-15 | 1979-06-27 | BASF Aktiengesellschaft | Verfahren zur Herstellung von Hydroxycitronellol |
US4347387A (en) * | 1980-12-04 | 1982-08-31 | Takasago Perfumery Co., Ltd. | Process for preparing hydroxycitronellal |
CN102503787A (zh) * | 2011-10-24 | 2012-06-20 | 合肥工业大学 | 一步法制备香茅醛的方法 |
WO2015070026A1 (en) * | 2013-11-11 | 2015-05-14 | Massachusetts Institute Of Technology | Nickel pre-catalysts and related compositions and methods |
CN110963902A (zh) * | 2019-12-05 | 2020-04-07 | 万华化学集团股份有限公司 | 一种水油两相不对称氢化合成r-香茅醛的方法及用于该方法的催化剂 |
CN110981707A (zh) * | 2019-12-19 | 2020-04-10 | 万华化学集团股份有限公司 | 一种橙花醇或香叶醇异构合成手性香茅醛的方法 |
CN112194686A (zh) * | 2020-10-29 | 2021-01-08 | 西安凯立新材料股份有限公司 | [(s)-(-)-2,2`-双(二苯基膦)-1,1`-联萘]二氯化铂的制备方法 |
CN112642489A (zh) * | 2020-12-23 | 2021-04-13 | 山东新和成药业有限公司 | 一种均相双金属络合催化剂、其制备方法及其在醇制备醛中的应用 |
CN114988990A (zh) * | 2022-06-15 | 2022-09-02 | 万华化学集团股份有限公司 | 一种香兰素的制备方法 |
Non-Patent Citations (1)
Title |
---|
"Combined lignin defunctionalisation and synthesis gas formation by acceptorless dehydrogenative decarbonylation";Zhenlei Zhang等;《Green Chemistry》;第22卷;第3791-3801 * |
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