72909-34-3

Basic information

• Product Name: Pyrroloquinoline quinone
• Synonyms: PQQ Cofactor, Pyrroloquinoline quinone, 4,5-Dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid;Pyrroloquinoline quinone ,98%;Coenzime PQQ;Coenzyme PQQ;Methoxatine;Pyrroloquinoline quinone,4,5-Dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid, Methoxatin, PQQ;4,5-Dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid;Pyrroloquinoline quinone(PQQ)
• CAS NO: 72909-34-3
• Molecular Formula: C₁₄H₆N₂O₈
• Molecular Weight: 330.21
• EINECS: 200-001-8
• Product Categories: All Inhibitors;Inhibitors;PQQ
• Mol File: 72909-34-3.mol
• Article Data: 27

Chemical Properties

• Boiling Point: 1018.6 °C at 760 mmHg
• Flash Point: 569.8 °C
• Appearance: /
• Density: 1.963 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.801
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 1.88±0.20(Predicted)
• Stability: Light and Temperature Sensitive
• BRN: 3596812
• CAS DataBase Reference: Pyrroloquinoline quinone(CAS DataBase Reference)
• NIST Chemistry Reference: Pyrroloquinoline quinone(72909-34-3)
• EPA Substance Registry System: Pyrroloquinoline quinone(72909-34-3)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• F: 8
• Hazardous Substances Data: 72909-34-3(Hazardous Substances Data)

Usage

Description

Pyrroloquinoline quinone (PQQ) is a novel biofactor for which a proposition can be made for physiological importance. PQQ was first recognized as an enzyme cofactor in bacteria. It has recently been tentatively identified as a component of interstellar dust. Thus, PQQ may have been present throughout early biological conception and evolution. PQQ is also a potent plant growth factor. Consequently, for animals and humans, there has been constant exposure to PQQ. In animals, PQQ is reported to participate in a range of biological functions with apparent survival benefits (e.g., improved neonatal growth and reproductive performance). There are also benefits from PQQ supplementation related to cognitive, immune, and antioxidant functions, as well as protection from cardiac and neurological ischemic events. Although PQQ is not currently viewed as a vitamin, its involvement in cell signaling pathways, particularly those important to mitochondriogenesis in experimental animal models, may eventually provide a rationale for defining PQQ as vital to life. For humans, such evidence suggests there may be similar parallels or benefits from improving PQQ status.

Uses

Pyrroloquinoline quinone is an important growth factor for the body and a redox/cofactor found in a a class of enzymes called quinoproteins. It is a cofactor of microbial quinoprotein enzyme, and imidazopyrroline. it regulates the level of free radicals in the body, protects the body; anti-oxidative damage; enhances mitochondrial function; detoxification; disease, etc.

Application

Pyrroloquinoline quinone has been used:as a component of nanocurcumin formulation (NCF), to study its therapeutic effect on ameliorate hypoxia-induced stress in hypertrophied cardiomyocytes.as a standard in fluorescence analysis.to test its efficiency in suppressing restrained oxidative stress and hepatic fibrogenesis in mouse models.Pyrroloquinoline quinone(PQQ) has been reported to function as a water soluble vitamin/cofactor and as an antioxidant. PQQ disodium salt is proposed for use due to its nutritive value in the United States (U.S.) in foods, such as energy, sport, and isotonic drinks; non-milk based meal replacement beverages; water (bottled, enhanced, fortified); milk-based meal replacement beverages; cereal and granola bars; and energy, meal replacement, and fortified bars. PQQ is also intended for use in dietary supplements.

General Description

Pyrroloquinoline Quinone (PQQ), also referred as methoxatin, is a water soluble orthoquinone molecule with redox-cycling ability.

Biochem/physiol Actions

Pyrroloquinoline Quinone (PQQ) plays a vital role in gluconic acid production and biosynthesis by microbes. It acts as an effective microbial growth stimulant and biological control determinant for plant pathogens. PQQ also acts as an anti-melanogenic agent and is used to treat disorders related to hyper pigmentation. It exhibits diverse role in metabolism and cell signaling pathways. PQQ is used as a potential therapeutic to treat liver fibrosis.

Purification Methods

Efflorescent yellow-orange needles of PQQ are formed on recrystallising from H2O by addition of Me2CO, or better from a supersaturated aqueous solution, as it forms an acetone adduct. [Forrest et al. Nature 280 843 1979.] It has also been purified by passage through a C-18 reverse phase silica cartridge or a silanized silica gel column in aqueous solution whereby methoxantin remains behind as a red-orange band at the origin. This band is collected and washed thoroughly with dilute aqueous HCl (pH 2) and is then eluted with MeOH/H2O (7:3) and evaporated in vacuo to give the coenzyme as a red solid. It has also been purified by dissolving it in aqueous 0.5M K2CO3 and acidified to pH 2.5 whereby PQQ precipitates as a deep red solid which is collected and dried in vacuo. Methoxantin elutes at 3.55 retention volumes from a C18 _Bondapak column using H2O/MeOH (95:5) + 0.1% AcOH pH 4.5. It has UV max at 247 and 330nm (shoulder at 270nm) in H2O and max at 250 and 340nm in H2O at pH 2.5. With excitation at ex 365nm it has a max emission at 483nm. The 13C NMR has : 113.86, 122.76, 125.97, 127.71, 130.68, 137.60, 144.63, 146.41, 147.62, 161.25, 165.48, 166.45, 173.30 and 180.00ppm. When a solution in 10% aqueous MeCO is adjusted to pH 9 with aqueous NH3 and kept at 25o for 30minutes, the acetone adduct is formed; UV has max at 250, 317 and 360nm (H2O, pH 5.5), and with ex at 360nm it has max fluorescence at max at 465nm; and the 13C NMR [(CD3)2SO, TMS] has : 29.77, 51.06, 74.82, 111.96, 120.75, 121.13, 125.59, 126.88, 135.21, 139.19, 144.92, 161.01, 161.47, 165.17, 168.61, 190.16 and 207.03ppm. It also forms a methanol adduct. When it is reacted with Me2SO4/K2CO3 in dry Me2NCHO at 80o for 4hours, it forms the trimethyl ester which has m 265-267o(dec) [260-263o(dec) also reported] after recrystallisation from hot MeCN (orange crystals) with UV max at 252 and 344nm (H2O) and 251, 321 and 373nm (in MeOH; MeOH adduct ). [Duine et al. Eur J Biochem 108 187 1980, Duine et al. Adv Enzymology 59 169 1987, Corey & Tramontano J Am Chem Soc 103 5599 1981, Gainor & Weinreb J Org Chem 46 4319 1981, Hendrickson & de Vries J Org Chem 17 1148 1982, McKenzie et al. J Chem Soc, Chem Commun 1372 1983.]

InChI:InChI=1/C14H6N2O8/c17-10-4-2-6(14(23)24)15-8(4)7-3(12(19)20)1-5(13(21)22)16-9(7)11(10)18/h1-2,15H,(H,19,20)(H,21,22)(H,23,24)

Synthetic route

trimethyl 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate (74447-88-4) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
With sodium carbonate In water at 30℃; for 24h;	100%
With water; potassium carbonate In water at 25 - 80℃; Green chemistry; Industrial scale;	91%
With potassium carbonate In water at 25 - 80℃; for 12h;	91%

5,5-Dimethoxy-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid trimethyl ester (78939-40-9) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
With potassium carbonate In water at 85℃; for 4h;	98%

4,5-Dihydro-4,5-dioxo-1H-pyrrolo<2,3-f>chinolin-2,7,9-tricarbonsaeure-(2-ethyl)(7,9-dimethyl)ester (80721-47-7) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Stage #1: 4,5-Dihydro-4,5-dioxo-1H-pyrrolo<2,3-f>chinolin-2,7,9-tricarbonsaeure-(2-ethyl)(7,9-dimethyl)ester With lithium hydroxide; water In tetrahydrofuran at 0 - 17℃; for 31.5h; Stage #2: With hydrogenchloride; potassium chloride In tetrahydrofuran; water at 0℃; for 1h; pH=5.3 - 6; Stage #3: With sulfuric acid In water at 20℃; for 2.5h;	97%
With lithium hydroxide In tetrahydrofuran; water at 25℃; for 6h;	89%
With lithium hydroxide In tetrahydrofuran for 6.5h;	89%

4,5-dihydroxy-4,5-dioxo-1H-pyrrolo{2,3-f}quinoline-2,7,9-tricarboxylic acid (79127-57-4) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
With dihydrogen peroxide at 35℃; for 24h;	86.5%
With acetate and phosphate buffer; potassium chloride; oxygen In water; dimethyl sulfoxide at 30℃; Rate constant; Kinetics; Mechanism;

5-Methoxy-1H-pyrrolo<2,3-f>quinoline-2,7,9-tricarboxylic acid (116451-31-1) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
With ammonium cerium (IV) nitrate In 1,2-dichloro-ethane at 25℃; for 24h;	19.01%

5-Methoxy-1H-pyrrolo<2,3-f>chinolin-2,7,9-tricarbonsaeure-(2-ethyl)(7,9-dimethyl)ester (133706-80-6) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 69 percent / Ce(NH4)2(NO3)6 / acetonitrile; H2O / 0.5 h / -3 °C 2: 63 percent / LiOH*H2O / tetrahydrofuran; H2O / 20.5 h / Ambient temperature; purification with conc. H2SO4 View Scheme
Multi-step reaction with 2 steps 1: copper(II) acetate monohydrate / water / 1 h / -5 °C 2: lithium hydroxide monohydrate / water; tetrahydrofuran / 32 h / 16 °C View Scheme

6-amino-5-methoxy-2-ethoxycarbonylindole (107575-60-0) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 73 percent / CH2Cl2 / 8 h / Ambient temperature 2: 94.5 percent / Cu(OAc)2*H2O, HCl(g)/air / CH2Cl2 3: 69 percent / Ce(NH4)2(NO3)6 / acetonitrile; H2O / 0.5 h / -3 °C 4: 63 percent / LiOH*H2O / tetrahydrofuran; H2O / 20.5 h / Ambient temperature; purification with conc. H2SO4 View Scheme
Multi-step reaction with 3 steps 1.1: dichloromethane / 12 h / 20 °C 1.2: 8 h / 20 °C 2.1: copper(II) acetate monohydrate / water / 1 h / -5 °C 3.1: lithium hydroxide monohydrate / water; tetrahydrofuran / 32 h / 16 °C View Scheme

6-(Formylamino)-5-methoxyindol-2-carbonsaeure-ethylester (119825-27-3) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 84.5 percent / 18percent aq. HCl / acetone / 4 h / 80 °C 2: 73 percent / CH2Cl2 / 8 h / Ambient temperature 3: 94.5 percent / Cu(OAc)2*H2O, HCl(g)/air / CH2Cl2 4: 69 percent / Ce(NH4)2(NO3)6 / acetonitrile; H2O / 0.5 h / -3 °C 5: 63 percent / LiOH*H2O / tetrahydrofuran; H2O / 20.5 h / Ambient temperature; purification with conc. H2SO4 View Scheme
Multi-step reaction with 4 steps 1.1: 1-(3-sulfopropyl)pyridinium phosphotungstate; benzylamine / 1.5 h / 140 °C / Microwave irradiation 2.1: dichloromethane / 12 h / 20 °C 2.2: 8 h / 20 °C 3.1: copper(II) acetate monohydrate / water / 1 h / -5 °C 4.1: lithium hydroxide monohydrate / water; tetrahydrofuran / 32 h / 16 °C View Scheme

4-oxo-pent-2-enedioic acid dimethyl ester (78939-37-4) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 73 percent / CH2Cl2 / 8 h / Ambient temperature 2: 94.5 percent / Cu(OAc)2*H2O, HCl(g)/air / CH2Cl2 3: 69 percent / Ce(NH4)2(NO3)6 / acetonitrile; H2O / 0.5 h / -3 °C 4: 63 percent / LiOH*H2O / tetrahydrofuran; H2O / 20.5 h / Ambient temperature; purification with conc. H2SO4 View Scheme
Multi-step reaction with 5 steps 1: CH2Cl2 / 7 h / 25 °C 2: dry hydrogen chloride / CH2Cl2 / 10 h 3: 60 percent / ceric ammonium nitrate / acetonitrile; H2O / 0.17 h / 0 °C 4: 92 percent / p-tuluenesulfonic acid / methanol / 4 h / Heating 5: 98 percent / 0.5 M K2CO3 / H2O / 4 h / 85 °C View Scheme
Multi-step reaction with 3 steps 1.1: dichloromethane / 12 h / 20 °C 1.2: 8 h / 20 °C 2.1: copper(II) acetate monohydrate / water / 1 h / -5 °C 3.1: lithium hydroxide monohydrate / water; tetrahydrofuran / 32 h / 16 °C View Scheme
Multi-step reaction with 5 steps 1: sulfuric acid / dichloromethane / 5 h / Reflux 2: potassium carbonate / 2-methyltetrahydrofuran / 5 h / Reflux 3: zinc; acetic acid / 10 h / 50 °C 4: sodium hydroxide / 24 h / 25 °C 5: ammonium cerium (IV) nitrate / 1,2-dichloro-ethane / 24 h / 25 °C View Scheme

cis-6,7,8,9-Tetrahydro-9-hydroxy-5-methoxy-1H-pyrrolo<2,3-f>chinolin-2,7,9-tricarbonsaeure-(2-ethyl)(7,9-dimethyl)ester → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94.5 percent / Cu(OAc)2*H2O, HCl(g)/air / CH2Cl2 2: 69 percent / Ce(NH4)2(NO3)6 / acetonitrile; H2O / 0.5 h / -3 °C 3: 63 percent / LiOH*H2O / tetrahydrofuran; H2O / 20.5 h / Ambient temperature; purification with conc. H2SO4 View Scheme

ethyl 5-hydroxyindole-2-carboxylate (24985-85-1) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 94 percent / Fremy's salt, KH2PO4 / acetonitrile; H2O / 0.5 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 3: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 4: 85 percent / trifluoroacetic acid / 1 h / 20 °C 5: 82 percent / chlorobenzene / 4 h / 131 °C 6: LiOH View Scheme
Multi-step reaction with 7 steps 1: 94 percent / Fremy's salt, KH2PO4 / acetonitrile; H2O / 0.5 h / 20 °C 2: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 3: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 4: Et3N, MnO2 / CH2Cl2 5: 85 percent / trifluoroacetic acid / 1 h / 20 °C 6: 82 percent / chlorobenzene / 4 h / 131 °C 7: LiOH View Scheme

4-Hydroxy-5-oxo-5H-indole-2-carboxylic acid ethyl ester (98126-24-0) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 2: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 3: 85 percent / trifluoroacetic acid / 1 h / 20 °C 4: 82 percent / chlorobenzene / 4 h / 131 °C 5: LiOH View Scheme
Multi-step reaction with 6 steps 1: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 2: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 3: Et3N, MnO2 / CH2Cl2 4: 85 percent / trifluoroacetic acid / 1 h / 20 °C 5: 82 percent / chlorobenzene / 4 h / 131 °C 6: LiOH View Scheme

2-Benzyloxycarbonylamino-4-nitro-pentanedioic acid dimethyl ester (204922-65-6) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 2: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 3: 85 percent / trifluoroacetic acid / 1 h / 20 °C 4: 82 percent / chlorobenzene / 4 h / 131 °C 5: LiOH View Scheme
Multi-step reaction with 6 steps 1: 47 percent / Et3N / tetrahydrofuran / 1 h / 20 °C 2: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 3: Et3N, MnO2 / CH2Cl2 4: 85 percent / trifluoroacetic acid / 1 h / 20 °C 5: 82 percent / chlorobenzene / 4 h / 131 °C 6: LiOH View Scheme

6-Chloro-4-hydroxy-7-[methoxycarbonyl-(4-methoxycarbonyl-2-oxo-2,3-dihydro-oxazol-5-yl)-methyl]-5-oxo-5H-indole-2-carboxylic acid ethyl ester (98126-30-8) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / chlorobenzene / 4 h / 131 °C 2: LiOH View Scheme

2-Benzyloxycarbonylamino-4-[2-ethoxycarbonyl-5-hydroxy-4-oxo-1,4-dihydro-indol-(7Z)-ylidene]-pentanedioic acid dimethyl ester → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 2: 85 percent / trifluoroacetic acid / 1 h / 20 °C 3: 82 percent / chlorobenzene / 4 h / 131 °C 4: LiOH View Scheme
Multi-step reaction with 5 steps 1: 1.) N-chlorosuccinimide, triethylamine; 2.) DDQ, Et3N / 1.) methylene chloride, 20 deg C, 30 min; 2.) methylene chloride, 20 deg C, 90 min 2: Et3N, MnO2 / CH2Cl2 3: 85 percent / trifluoroacetic acid / 1 h / 20 °C 4: 82 percent / chlorobenzene / 4 h / 131 °C 5: LiOH View Scheme

(Z)-4-[(Z)-Benzyloxycarbonylimino]-2-(6-chloro-2-ethoxycarbonyl-4-hydroxy-5-oxo-5H-indol-7-yl)-pent-2-enedioic acid dimethyl ester → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / trifluoroacetic acid / 1 h / 20 °C 2: 82 percent / chlorobenzene / 4 h / 131 °C 3: LiOH View Scheme

2-Benzyloxycarbonylamino-4-(6-chloro-2-ethoxycarbonyl-4-hydroxy-5-oxo-5H-indol-7-yl)-pentanedioic acid dimethyl ester (98126-27-3, 98126-28-4) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N, MnO2 / CH2Cl2 2: 85 percent / trifluoroacetic acid / 1 h / 20 °C 3: 82 percent / chlorobenzene / 4 h / 131 °C 4: LiOH View Scheme

3-Amino-4,5-dihydroxy-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (80721-45-5) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 89 percent / concd. HCl, aq. NaNO2 / 0.33 h / 0 °C 2: HOAc, 50percent aq. H3PO2 / 1 h / Ambient temperature 3: 89 percent / aq. LiOH / tetrahydrofuran / 6.5 h View Scheme
Multi-step reaction with 3 steps 1: NaNO2, concd HCl / 30 h / 0 °C 2: 1.) 50percent hypophosphorous acid, 2.) aq. basic potassium ferricyanide / 1.) acetic acid, 25 deg C, 20 min 3: 89 percent / LiOH / H2O; tetrahydrofuran / 6 h / 25 °C View Scheme

3-Diazo-4,5-dioxo-4,5-dihydro-3H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (80721-46-6) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: HOAc, 50percent aq. H3PO2 / 1 h / Ambient temperature 2: 89 percent / aq. LiOH / tetrahydrofuran / 6.5 h View Scheme
Multi-step reaction with 2 steps 1: 1.) 50percent hypophosphorous acid, 2.) aq. basic potassium ferricyanide / 1.) acetic acid, 25 deg C, 20 min 2: 89 percent / LiOH / H2O; tetrahydrofuran / 6 h / 25 °C View Scheme

3-Nitro-4,5-dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (80721-44-4) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 98 percent / H2 / PtO2 / methanol / 3 h 2: 89 percent / concd. HCl, aq. NaNO2 / 0.33 h / 0 °C 3: HOAc, 50percent aq. H3PO2 / 1 h / Ambient temperature 4: 89 percent / aq. LiOH / tetrahydrofuran / 6.5 h View Scheme
Multi-step reaction with 4 steps 1: 100 percent / H2 / 10percent Pd/C / methanol / 4 h / 760 Torr 2: NaNO2, concd HCl / 30 h / 0 °C 3: 1.) 50percent hypophosphorous acid, 2.) aq. basic potassium ferricyanide / 1.) acetic acid, 25 deg C, 20 min 4: 89 percent / LiOH / H2O; tetrahydrofuran / 6 h / 25 °C View Scheme

trimethyl 4,5-dimethoxy-1H-pyrrolo<2,3-f>quinoline-2,7,9-tricarboxylate (78891-39-1) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 60 percent / AgO, HNO3 / tetrahydrofuran / 0.17 h / Ambient temperature 2: 75 percent / LiOH, H2O / tetrahydrofuran / 5 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: 66 percent / AgO, 6 N HNO3 / tetrahydrofuran / 0.17 h 2: 75 percent / H2O, LiOH / tetrahydrofuran / 5.5 h View Scheme

dimethyl 7,8-dimethoxy-6-<3-methoxy-3-oxo-2-(phenylhydrazono)propyl>-5-nitro-2,4-quinolinedicarboxylate (78891-38-0) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 62 percent / H2, HCl / 10percent Pd/C / methanol 2: 60 percent / AgO, HNO3 / tetrahydrofuran / 0.17 h / Ambient temperature 3: 75 percent / LiOH, H2O / tetrahydrofuran / 5 h / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: 66 percent / H2, 5percent HCl / 5percent Pd/C / methanol / 2 h / Ambient temperature 2: 66 percent / AgO, 6 N HNO3 / tetrahydrofuran / 0.17 h 3: 75 percent / H2O, LiOH / tetrahydrofuran / 5.5 h View Scheme

dimethyl 2-ketoglutarate (13192-04-6) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: Br2 / CH2Cl2 / Heating 2: Et3N / diethyl ether / 20 h / 25 °C 3: CH2Cl2 / 7 h / 25 °C 4: dry hydrogen chloride / CH2Cl2 / 10 h 5: 60 percent / ceric ammonium nitrate / acetonitrile; H2O / 0.17 h / 0 °C 6: 92 percent / p-tuluenesulfonic acid / methanol / 4 h / Heating 7: 98 percent / 0.5 M K2CO3 / H2O / 4 h / 85 °C View Scheme

3-bromo-2-oxopentane-1,5-dioic acid dimethyl ester (148728-48-7) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: Et3N / diethyl ether / 20 h / 25 °C 2: CH2Cl2 / 7 h / 25 °C 3: dry hydrogen chloride / CH2Cl2 / 10 h 4: 60 percent / ceric ammonium nitrate / acetonitrile; H2O / 0.17 h / 0 °C 5: 92 percent / p-tuluenesulfonic acid / methanol / 4 h / Heating 6: 98 percent / 0.5 M K2CO3 / H2O / 4 h / 85 °C View Scheme

6-Formylamino-5-methoxy-1H-indole-2-carboxylic acid methyl ester (78939-35-2) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 79 percent / hydrochloric acid / acetone; H2O / 1 h / Heating 2: CH2Cl2 / 7 h / 25 °C 3: dry hydrogen chloride / CH2Cl2 / 10 h 4: 60 percent / ceric ammonium nitrate / acetonitrile; H2O / 0.17 h / 0 °C 5: 92 percent / p-tuluenesulfonic acid / methanol / 4 h / Heating 6: 98 percent / 0.5 M K2CO3 / H2O / 4 h / 85 °C View Scheme

9-Hydroxy-5-methoxy-6,7,8,9-tetrahydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid trimethyl ester (78939-38-5) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: dry hydrogen chloride / CH2Cl2 / 10 h 2: 60 percent / ceric ammonium nitrate / acetonitrile; H2O / 0.17 h / 0 °C 3: 92 percent / p-tuluenesulfonic acid / methanol / 4 h / Heating 4: 98 percent / 0.5 M K2CO3 / H2O / 4 h / 85 °C View Scheme
Multi-step reaction with 3 steps 1: copper(II) acetate monohydrate; formic acid / 48 h / 25 °C 2: ammonium cerium (IV) nitrate / acetonitrile; water / 2 h / -5 °C 3: potassium carbonate / water / 12 h / 25 - 80 °C View Scheme

6-amino-5-methoxy-2-methoxycarbonylindole (78939-36-3) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: CH2Cl2 / 7 h / 25 °C 2: dry hydrogen chloride / CH2Cl2 / 10 h 3: 60 percent / ceric ammonium nitrate / acetonitrile; H2O / 0.17 h / 0 °C 4: 92 percent / p-tuluenesulfonic acid / methanol / 4 h / Heating 5: 98 percent / 0.5 M K2CO3 / H2O / 4 h / 85 °C View Scheme
Multi-step reaction with 4 steps 1: dichloromethane / 25 °C / Green chemistry; Industrial scale 2: copper(II) acetate monohydrate; formic acid / 25 °C / Green chemistry; Industrial scale 3: ammonium cerium (IV) nitrate / acetonitrile / -5 °C / Green chemistry; Industrial scale 4: potassium carbonate; water / water / 25 - 80 °C / Green chemistry; Industrial scale View Scheme
Multi-step reaction with 4 steps 1: dichloromethane / 16 h / 25 °C 2: copper(II) acetate monohydrate; formic acid / 48 h / 25 °C 3: ammonium cerium (IV) nitrate / acetonitrile; water / 2 h / -5 °C 4: potassium carbonate / water / 12 h / 25 - 80 °C View Scheme

5-methoxy-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid trimethyl ester (78939-39-6) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 60 percent / ceric ammonium nitrate / acetonitrile; H2O / 0.17 h / 0 °C 2: 92 percent / p-tuluenesulfonic acid / methanol / 4 h / Heating 3: 98 percent / 0.5 M K2CO3 / H2O / 4 h / 85 °C View Scheme
Multi-step reaction with 2 steps 1: ammonium cerium (IV) nitrate / acetonitrile / -5 °C / Green chemistry; Industrial scale 2: potassium carbonate; water / water / 25 - 80 °C / Green chemistry; Industrial scale View Scheme
Multi-step reaction with 2 steps 1: ammonium cerium (IV) nitrate / acetonitrile; water / 2 h / -5 °C 2: potassium carbonate / water / 12 h / 25 - 80 °C View Scheme

methyl 4-(acetylamino)-o-anisate (4093-29-2) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / 0 °C 2: 80 percent / manganese (IV) oxide / CHCl3; methanol / 20 h / Ambient temperature 3: 73 percent / NaOMe / methanol / 2 h / -15 °C 4: 87 percent / xylene / 4 h / Heating 5: 85 percent / HCl / methanol / 6 h / Heating 6: 2.) HCl / 1.) CH2Cl2, room temp., 12 h; 2.) 12 h, ether 7: 1.) BBr3; 2.) MeOH, H2SO4 (96percent) / 1.) CH2Cl2, room temp., 140 h; 2.) reflux, 48 h 8: 93 percent / benzoyl t-butyl nitroxide / methanol; CHCl3 / 16 h / Ambient temperature View Scheme
Multi-step reaction with 10 steps 1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / 0 °C 2: 80 percent / manganese (IV) oxide / CHCl3; methanol / 20 h / Ambient temperature 3: 73 percent / NaOMe / methanol / 2 h / -15 °C 4: 87 percent / xylene / 4 h / Heating 5: 85 percent / HCl / methanol / 6 h / Heating 6: 2.) HCl / 1.) CH2Cl2, room temp., 12 h; 2.) 12 h, ether 7: 8.7 mg / NH4NO3 / trifluoroacetic acid / 3.75 h / Ambient temperature 8: 93 percent / H2 / 10percent palladium-on-charcoal / methanol / 20 h 9: 73 percent / MnO2 / aq. H2SO4 / 0.75 h / 0 °C View Scheme

methyl 4-acetamido-2-hydroxybenzoate (4093-28-1) → pyrroloquinoline quinone (72909-34-3)

Conditions	Yield
Multi-step reaction with 10 steps 1: 97 percent / potassium carbonate / acetone / 8 h / Heating 2: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / 0 °C 3: 80 percent / manganese (IV) oxide / CHCl3; methanol / 20 h / Ambient temperature 4: 73 percent / NaOMe / methanol / 2 h / -15 °C 5: 87 percent / xylene / 4 h / Heating 6: 85 percent / HCl / methanol / 6 h / Heating 7: 2.) HCl / 1.) CH2Cl2, room temp., 12 h; 2.) 12 h, ether 8: 1.) BBr3; 2.) MeOH, H2SO4 (96percent) / 1.) CH2Cl2, room temp., 140 h; 2.) reflux, 48 h 9: 93 percent / benzoyl t-butyl nitroxide / methanol; CHCl3 / 16 h / Ambient temperature View Scheme
Multi-step reaction with 11 steps 1: 97 percent / potassium carbonate / acetone / 8 h / Heating 2: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / 0 °C 3: 80 percent / manganese (IV) oxide / CHCl3; methanol / 20 h / Ambient temperature 4: 73 percent / NaOMe / methanol / 2 h / -15 °C 5: 87 percent / xylene / 4 h / Heating 6: 85 percent / HCl / methanol / 6 h / Heating 7: 2.) HCl / 1.) CH2Cl2, room temp., 12 h; 2.) 12 h, ether 8: 8.7 mg / NH4NO3 / trifluoroacetic acid / 3.75 h / Ambient temperature 9: 93 percent / H2 / 10percent palladium-on-charcoal / methanol / 20 h 10: 73 percent / MnO2 / aq. H2SO4 / 0.75 h / 0 °C View Scheme

serin (302-84-1) + pyrroloquinoline quinone (72909-34-3) → C15H7N3O7 (132847-84-8)

Conditions	Yield
In water at 30℃; for 24h; pH = 9.7;	100%
With air; cetyltrimethylammonim bromide at 30℃;	55%

aminoguanidine sulfate (996-19-0) + pyrroloquinoline quinone (72909-34-3) → 4,5-dihydroxy-4,5-dioxo-1H-pyrrolo{2,3-f}quinoline-2,7,9-tricarboxylic acid (79127-57-4)

Conditions	Yield
With sodium hydrogencarbonate for 24h;	100%
at 30℃; Mechanism; pH 10;

pyrroloquinoline quinone (72909-34-3) → 4,5-dihydroxy-4,5-dioxo-1H-pyrrolo{2,3-f}quinoline-2,7,9-tricarboxylic acid (79127-57-4)

Conditions	Yield
With phenylhydrazine hydrochloride In methanol at 50℃; for 0.166667h;	100%
With thiophenol In acetonitrile for 2h;	84%
With acetate buffer; thiophenol In water; acetonitrile at 30℃;	84 % Spectr.
With methylhydrazine In various solvent(s) at 30℃; Rate constant; anaerobic conditions;
With hydrogenchloride; ascorbic acid In water at 12 - 20℃; for 23h; pH=2.96;	3.35 g

pyrroloquinoline quinone (72909-34-3) + glycine (56-40-6) → C15H7N3O7 (132847-84-8)

Conditions	Yield
In water at 30℃; for 24h; pH = 6.6;	100%
at 30℃; Rate constant; Mechanism; Product distribution; pH = 9.1; other pH values; other aminoacids;
With phosphate buffer pH 6.5; bovine serum In water Rate constant; Ambient temperature; pH range of 3.0 - 9.0;

pyrroloquinoline quinone (72909-34-3) + 1,2-diamino-benzene (95-54-5) → 3H-3,7,8,13-Tetraaza-benzo[a]cyclopenta[c]anthracene-2,4,6-tricarboxylic acid

Conditions	Yield
In N,N-dimethyl-formamide Ambient temperature;	96%

pyrroloquinoline quinone (72909-34-3) + 6,7-Dimethoxy-quinoxaline-2,3-diamine → C24H14N6O8

Conditions	Yield
In N,N-dimethyl-formamide Ambient temperature;	95%

pyrroloquinoline quinone (72909-34-3) + dimethyl sulfate (77-78-1) → trimethyl 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylate (74447-88-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Schlenk technique; Inert atmosphere;	91%
With potassium carbonate In N,N-dimethyl-formamide at 25℃; Inert atmosphere;	57%
With potassium carbonate In N,N-dimethyl-formamide at 25℃;
With hydrogenchloride; potassium carbonate In water; N,N-dimethyl-formamide at 20 - 50℃; for 72.5h; Large scale;

pyrroloquinoline quinone (72909-34-3) → 4,5-dihydroxy-1H-pyrrolo[2,3-f]chinoline-2,7,9-tricarboxylic acid trilithium salt

Conditions	Yield
With lithium hydroxide monohydrate In tetrahydrofuran; water at 15 - 20℃; for 24h;	90.5%

pyrroloquinoline quinone (72909-34-3) → trilithium pyrroloquinoline quinone

Conditions	Yield
With lithium hydroxide monohydrate In tetrahydrofuran; water at 15 - 20℃; for 24h;	90.5%
With lithium hydroxide In water at 0 - 5℃; for 2h;	10 mg

pyrroloquinoline quinone (72909-34-3) → 5-Diazo-4,5-dihydro-4-oxo-1H-pyrrolo<2,3-f>chinolin-2,7,9-tricarbonsaeure

Conditions	Yield
With phosphate buffer; toluene-4-sulfonic acid hydrazide In tetrahydrofuran 1.) 2 h, 10 deg C, 2.) 3 h, room temperature;	88%

pyrroloquinoline quinone (72909-34-3) → 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid disodium salt

Conditions	Yield
With sodium hydroxide at 25℃; for 3h; Reagent/catalyst;	88%

pyrroloquinoline quinone (72909-34-3) + ethylenediamine (107-15-3) → 1H-1,4,7,8-Tetraaza-cyclopenta[l]phenanthrene-2,9,11-tricarboxylic acid

Conditions	Yield
With CTAB micellar system at 50℃; for 1h; Mechanism; further α,ω-diaminoalkanes;	87%
With CTAB micellar system at 50℃; for 1h;	87%

O-phospho-DL-serine (17885-08-4) + pyrroloquinoline quinone (72909-34-3) → C16H10N3O11P (144219-06-7)

Conditions	Yield
In water at 30℃; for 24h; pH = 9.6;	86%

pyrroloquinoline quinone (72909-34-3) → 4,5-dihydroxy-1H-pyrrolo[2,3-f]chinoline-2,7,9-tricarboxylic acid dilithium salt

Conditions	Yield
With lithium hydroxide monohydrate In tetrahydrofuran; water at 15 - 20℃; for 24h;	83.9%

pyrroloquinoline quinone (72909-34-3) → 4,5-dihydroxy-1H-pyrrolo[2,3-f]chinoline-2,7,9-tricarboxylic acid lithium salt

Conditions	Yield
With lithium hydroxide monohydrate In tetrahydrofuran; water at 15 - 20℃; for 24h;	83.9%

pyrroloquinoline quinone (72909-34-3) → 4,5-dihydroxy-1H-pyrrole[2,3-f]chinoline-2,7,9-tricarboxylic acid, dilithium salt

Conditions	Yield
With lithium hydroxide monohydrate In tetrahydrofuran; water at 15 - 20℃; for 24h;	83.9%

pyrroloquinoline quinone (72909-34-3) → 4,5-dihydroxy-1H-pyrrole[2,3-f]chinoline-2,7,9-tricarboxylic acid, lithium salt (1246998-46-8)

Conditions	Yield
With lithium hydroxide monohydrate In tetrahydrofuran; water at 15 - 20℃; for 24h;	83.9%

betaine (107-43-7) + pyrroloquinoline quinone (72909-34-3) → C14H6N2O8*C5H11NO2

Conditions	Yield
In ethanol at 25 - 30℃; for 24h;	81%

pyrroloquinoline quinone (72909-34-3) + D,L-histidine (71-00-1) → C19H11N5O7 (144219-04-5)

Conditions	Yield
In water at 30℃; for 24h; pH = 6.7;	80%

pyrroloquinoline quinone (72909-34-3) + 2-Amino-1-phenylethanol (7568-93-6) → C15H7N3O7 (132847-84-8)

Conditions	Yield
With cetyltrimethylammonim bromide In water at 30℃; for 24h; pH = 10.4;	78%

pyrroloquinoline quinone (72909-34-3) + ›Tyr (556-02-5, 556-03-6, 34537-57-0, 55520-40-6, 96946-98-4, 60-18-4) → (4-hydroxyphenyl)methanol (623-05-2) + C15H7N3O7 (132847-84-8)

Conditions	Yield
With air; cetyltrimethylammonim bromide at 30℃;	A n/a B 77%

pyrroloquinoline quinone (72909-34-3) + ›Tyr (556-02-5, 556-03-6, 34537-57-0, 55520-40-6, 96946-98-4, 60-18-4) → C15H7N3O7 (132847-84-8)

Conditions	Yield
In water at 30℃; for 24h; carbonate buffer, pH = 10.0;	77%

3-methoxy-2-aminopropionic acid (19794-53-7) + pyrroloquinoline quinone (72909-34-3) → C17H11N3O8 (144219-05-6)

Conditions	Yield
In water at 30℃; for 24h; pH = 9.8;	72%

pyrroloquinoline quinone (72909-34-3) + Trp (54-12-6) → C15H7N3O7 (132847-84-8)

Conditions	Yield
In water at 30℃; for 24h; pH = 6.7;	71%

DL-threonine (72-19-5, 80-68-2, 144-98-9, 632-20-2, 2676-21-3, 7004-04-8, 24830-94-2, 28954-12-3, 36676-50-3) + pyrroloquinoline quinone (72909-34-3) → C15H7N3O7 (132847-84-8)

Conditions	Yield
With air; cetyltrimethylammonim bromide at 30℃;	70%
In water at 30℃; for 24h; pH = 10.2;	70%

Upstream product

• 78939-40-9 5,5-Dimethoxy-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid trimethyl ester 
• 4093-28-1 methyl 4-acetamido-2-hydroxybenzoate 
• 38256-25-6 dimethyl (E)-2-oxoglutaconate 
• 67827-72-9 2-methoxy-5-nitroaniline hydrochloride 
• 5965-53-7 diethyl 2-ketoglutarate 
• 81770-66-3 4,5-dimethoxy-1H-pyrrolo<2,3-f>quinoline-2,7,9-tricarboxylic acid 
• 33721-54-9 N-(2-methoxy-5-nitrophenyl)acetamide 
• 99-59-2 3-amino-4-methoxynitrobenzene 
• 149686-06-6 N-(2-methoxyl-5-nitrophenyl)formamide 
• 328-50-7 α-ketoglutaric acid 
• 78939-34-1 N-(5-amino-2-methoxylphenyl)formamide 
• 107575-59-7 ethyl pyruvate 3-formamido-4-methoxyphenyl-hydrazone 
• 119825-27-3 6-(Formylamino)-5-methoxyindol-2-carbonsaeure-ethylester 
• 107575-60-0 6-amino-5-methoxy-2-ethoxycarbonylindole 

Downstream Products

• 79127-57-4 4,5-dihydroxy-4,5-dioxo-1H-pyrrolo{2,3-f}quinoline-2,7,9-tricarboxylic acid 
• 623-05-2 (4-hydroxyphenyl)methanol 
• 132847-84-8 C₁₅H₇N₃O₇ 
• 144219-07-8 C₁₈H₁₃N₃O₇ 
• 73030-04-3 4,5-dihydro-5-hydroxy-4-oxo-5-(2-oxopropyl)-1H-pyrrolo<2,3-f>quinoline-2,7,9-tricarboxylic acid 
• 132847-85-9 C₂₁H₁₁N₃O₇ 
• 882-33-7 diphenyldisulfane 
• 123030-19-3 5-Amino-4-hydroxy-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid 
• 100-52-7 benzaldehyde 

Relevant articles and documents

Reaction of Reduced PQQ (PQQH2) and Molecular Oxygen

Reduced PQQ (PQQH2) is prepared by the reaction of PQQ with thiophenol, 1-benzyl-1,4-dihydronicotinamide (BNAH), sodium dithionite, or sodium borohydride.Oxidation of PQQH2 to PQQ by molecular oxygen in aqueous solutions is investigated kinetically.The oxidation is accelerated gradually with proceeding of the reaction, which may be attributed to the side reaction of PQQH2 and H2O2 produced by the reaction of PQQH2 and O2.As in fact, the yield of H2O2 is found to be 50percent based on PQQH2.Initial rate is first-order in oxygen concentration.The pH-rate profile suggests that an active species in the reaction is PQQH-.Autocatalysis of O2-. and PQQ itself is scarcely detected in this reaction.The mechanism of the oxidation is also discussed.

Unusual Ionic Bond and Solubility Mechanism of NanPQQ (n = 0-4) Crystals

A comparative study of van der Waals and ionic crystals can provide vital information for the medical and food industries. In this work, we investigated the coenzyme pyrroloquinoline quinone (PQQ), which contains three carboxyl groups coupled to imidazole, pyridine, and quinone. Whole-crystal analysis (crystal-ome) was attempted for NanPQQ (n = 0-4) crystals. All deprotonation sites were found to be dependent on pKa except for the Na sites, which cannot be explained by pKa. The Na1PQQ crystal exhibited an unusual ionic bond, forming COOH-Na+ at one of the carboxyl sites in the structure. The difference in the solubility of the van der Waals and ionic crystals was also investigated, with a focus on the dissolution processes of Na0PQQ and Na2PQQ, by combining molecular dynamics simulations with experiments that define the crystal surfaces. This study is the first step toward developing a general rule to link the different types of crystal structures with different dissolution mechanisms and rates.

Multistep, eight-electron oxidation catalyzed by the cofactorless oxidase, PqqC: Identification of chemical intermediates and their dependence on molecular oxygen

The final step of the biosynthesis of prokaryotic cofactor PQQ is catalyzed by PqqC, a cofactorless oxidase that brings about a ring closure and overall eight-electron oxidation of its substrate. Time-dependent acid quenching and subsequent high-performance liquid chromatography separation and mass spectrometric analyses of reaction mixtures were performed to correlate the structures of intermediates with previously observed UV-visible signatures. The reaction is composed of four stepwise oxidations: three steps use O2 as the two-electron acceptor, and the fourth uses hydrogen peroxide (H 2O2). The chemical nature of the intermediates, the stoichiometry of the reaction, and their dependence on the oxygen concentration indicate that the third oxidation uses the product, H2O2, from the preceding step to produce water. The last oxidation step can also be studied separately and is a reaction between O2 and PQQH2 trapped in the active site. This oxidation is approximately 10 times slower than the reoxidation of PQQH2 in solution. From the order of the four oxidation steps and their sensitivity to O2 concentration, we propose a progressive closure of the active site as the enzyme proceeds through its catalytic cycle.

PYRROLOQUINOLINE QUINONE MONOSODIUM AND METHOD FOR PRODUCING THE SAME, AND COMPOSITION COMPRISING THE SAME

The present invention provides pyrroloquinoline quinone monosodium having a structure represented by the following formula (1).

A method for synthesizing pyrroloquinoline quinone (by machine translation)

The invention relates to a synthetic pyrroloquinoline quinone of the method, the method to pyruvic acid ethyl ester as the starting synthetic raw material, preparation pyrroloquinoline quinone. In the synthetic method of the present invention, compound 4 synthesis of compound 5 is the key step in the synthetic route, in the key step 5) in, the invention creative use of hexafluoro antimonate ion liquid, hexafluoro titanate ion liquid, six fluorine niobium acid salt ion liquid such as Lewis acid ionic liquid, the ionic liquid has the function of the reaction medium and the catalyst, thereby improving the response speed and the yield of this step. In addition, the invention preferably use the [BMIm] SbF6 Ionic liquid, [BMIm] SbF6 Ionic liquid and Sc (OTf)3 Can be formed of a higher catalytic activity [Sc (OTf)3 -x ] [SbF6 ], Can make the reaction efficiency is greatly improved, and the obtained reaction product in [BMIm] SbF6 The solubility of the ionic liquid in small, easily precipitated, so as to improve the reaction yield (can be up to 96%). (by machine translation)