Name: 4707-32-8|2,2-Dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione|98%
Brand: Ambeed
SKU: A951815
Price: 13.0 USD
Availability: InStock
Rating: 92 (29 reviews)

1
[ 4707-32-8 ]
[ 108-24-7 ]
[ 856209-25-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium acetate; zinc; for 1h;Heating / reflux;	12.0 g of <strong>[4707-32-8]2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione</strong>, 16.1 g of zinc powder, 50 mL of anhydrous acetic acid, and 2.0 g of sodium acetate were mixed and vigorously stirred under reflux for 1 hour. The reaction mixture was cooled to room temperature and filtered. The filtered solid was washed once with 200 mL of EtOAc. The filtrate was distilled under reduced pressure to remove anhydrous acetic acid and EtOAc. The residue was dissolved in 200 mL of CH2Cl2 and washed with water. The organic extract was dried over Na2SO4 and concentrated under reduced pressure. The residue was recrystallized from 150 mL of isopropanol, such that the unpurified final product reached a purity of 99% or higher. 14.8 g (yield: 92%) of the title compound was obtained as a pure white solid crystal. 1H-NMR (CDCl3, delta): 8.20 (d, 1H, J=4.5 Hz), 7.67 (d, 1H, J=4.5 Hz), 7.46 (t, 1H, J=4.5 Hz), 7.41 (t, 1H, J=4.5 Hz), 2.67 (t, 1H, J=6.5 Hz), 2.40 (s, 2H), 2.33 (s, 3H), 1.84 (t, 1H, J=6.5 Hz).

Reference： [1]Patent: US2009/124680,2009,A1 .Location in patent: Page/Page column 14
[2]Gazzetta Chimica Italiana,1915,vol. 45 II,p. 56
Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti,1915,vol. <5> 24 I,p. 1062

2
[ 4707-32-8 ]
[ 95-54-5 ]
[ 6537-44-6 ]

Reference： [1]Magnetic Resonance in Chemistry,1998,vol. 36,p. 529 - 532
[2]Synthetic Communications,2007,vol. 37,p. 113 - 118
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2008,vol. 47,p. 427 - 433
[4]Journal of the American Chemical Society,1936,vol. 58,p. 1190,1195
[5]European Journal of Medicinal Chemistry,2009,vol. 44,p. 2334 - 2337
[6]Journal of the Indian Chemical Society,2010,vol. 87,p. 85 - 95

3
[ 4707-32-8 ]
[ 16274-33-2 ]

Reference： [1]Journal of the Chemical Society,1896,vol. 69,p. 1365

4
[ 4707-32-8 ]
[ 4707-33-9 ]

Reference： [1]Journal of the Chemical Society,1892,vol. 61,p. 638
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2008,vol. 47,p. 1865 - 1870
[3]Journal of Organic Chemistry,2015,vol. 80,p. 7340 - 7350
[4]ChemPlusChem,2019,vol. 84,p. 52 - 61

5
[ 4707-32-8 ]
[ 104433-23-0 ]

Reference： [1]Gazzetta Chimica Italiana,1889,vol. 19,p. 611

6
[ 4707-32-8 ]
[ 15298-01-8 ]

Reference： [1]Journal of the Chemical Society,1892,vol. 61,p. 638
[2]Journal of Pharmacy and Pharmacology,2011,vol. 63,p. 1156 - 1160

7
[ 4707-32-8 ]
[ 856209-25-1 ]

Reference： [1]Gazzetta Chimica Italiana,1889,vol. 19,p. 611

8
[ 4707-32-8 ]
[ 111479-51-7 ]

Reference： [1]Journal of the Chemical Society,1892,vol. 61,p. 638

9
[ 4707-33-9 ]
[ 4707-32-8 ]

Reference： [1]Journal of the Chemical Society,1892,vol. 61,p. 638
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2008,vol. 47,p. 1865 - 1870

10
[ 84-79-7 ]
[ 4707-32-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sulfuric acid;	Sulfuric acid was slowly added to lapachol (1 mmol, 242 mg) until complete dissolution of the quinone and formation of a red solution. Then, the solution was poured into ice and the precipitate formed was filtered off and washed with water. beta-Lapachone was recrystallized in ethanol and obtained as an orange solid (240 mg, 99% yield); mp 153-155 C. H NMR (400 MHz, CDCb, 303 K) <5: 8.06 (dd, 1 H, J = 7.6 and 1 .4 Hz), 7.81 (dd, 1 H, J = 7.8 and 1 .1 Hz), 7.65 (ddd, 1 H, J = 7.8, 7.6 and 1.4 Hz), 7.51 (td, 1 H, J = 7.6, 7.6 and 1 .1 Hz), 2.57 (t, 2H, J = 6.7 Hz), 1 .86 (t, 2H, J = 6.7 Hz), 1 .47 (s, 6H). 13C NMR (100 MHz, CDCb, 303 K) delta: 179.8, 178.5, 162.0, 134.7, 132.6, 130.6, 130.1 , 128.5, 124.0, 1 12.7, 79.3, 31 .6, 26.8, 16.2. The data are consistent with those reported in the literature (see 42 and 43).
97%	With niobium pentachloride; In dichloromethane; at 20℃; for 4h;	To a solution of lapachol (2) (1 g, 4.13 mmol) in DCM (50 mL) was added the Lewis acid NbCl5 (5.58 g, 20.66 mmol). The mixture was stirred at room temperature for 4 h. Then the reaction mixture was poured into cooled water (100 mL), extracted with ethyl acetate (3*100 mL), and washed with brine (100 mL). The organic layer was combined, dried over sodium sulfate, and concentrated under reduced pressure to give the pure product beta-lapachone (1) (0.973 g, 97%) without any need for further purification.
90%	With sulfuric acid; In dichloromethane; at 25℃; for 3h;	To a stirred solution of lapachol (1), (242 mg, 1.0 mmol, 1equiv) in CH2Cl2 (7 mL) was added conc. H2SO4 (0.8 ml,1.5 mmol, 1.5 equiv), the resulting reaction mixture wasstirred for 3 h, at room temperature. The orange suspensionwas filtered and washed with ice cold water (3 × 5 ml), thecrude product was dried under vacuum and column chromatographicpurification of the crude compound over silicagel using 20-30% EtOAc in hexane as solvent gradientafforded pure beta-lapachone (2) (218 mg, 90% yield), as anorange solid (Eyong et al. 2013).

84%	With toluene-4-sulfonic acid; In dichloromethane; at 30℃;	To a stirred solution of 2 (70 mg, 0.29 mmol) in dry dichloromethane(10 mL), p-toluenesulfonic acid (70 mg, 0.41 mmol) wasadded and further stirred at room temperature for 2 h. The reactionmixture was filtered and the filtrate was evaporated. Residue wastaken in ethyl acetate (25 mL) and washed with water. Organicphase was dried with anhydrous Na2SO4 and concentrated invacuo. The residue was purified through a filter column of silicagel (hexane-ethyl acetate) to get 3 as orange coloured solid.Yield 59 mg (84%); mp 151-152.5 C [154-55 C]17b; IR (KBr)mmax 3399, 3019, 1732, 1654, 1384, 1215, 1047; 1H NMR (CDCl3,300 MHz) d 1.22 (s, 3H), 1.25 (s, 3H), 1.80-1.85 (t, J = 6.5 Hz, 2H),2.51-2.56 (t, J = 6.5 Hz, 2H), 7.44-7.49 (t, J = 7.5 Hz, 1H), 7.59-7.63 (t, J = 7.1 Hz, 1H), 7.77-7.79 (d, J = 7.5 Hz, 1H), 8.00-8.02 (d,J = 7.5 Hz, 1H). 13C NMR (CDCl3, 75 MHz) d 16.5, 27.1, 27.1, 32.0,79.7, 113.1, 124.4, 128.9, 130.5, 131.0, 133.0, 135.2, 162.4, 178.9,180.2; Electrospray mass (MeOH) 243 [M+H]+, 265 [M+Na]+, 281[M+K]+; Negative mode 241 [MH]; HRMS (ESI-TOF) m/z [M+H]+calcd for C15H15O3 243.1021, found 243.1020; m/z [M+Na]+calcd for C15H14O3Na 265.0840, found 265.0837.
		Example 1: Synthesis of beta-lapachone (Compound 1) <n="52"/>17.4 g (0.10M) of 2-hydroxy-l,4-naphthoquinone was dissolved in 120 ml of DMSO, and 0.88 g (0.1 IM) of LiH was gradually added thereto. Here, this should be done with care because hydrogen evolves. The reaction solution was stirred, and after confirming no further production of hydrogen, was additionally stirred for another 30 min. Then, 15.9 g (0.10M) of prenyl bromide (1- bromo-3-methyl-2-butene) and 3.35 g (0.025M) of LiI were gradually added thereto. The reaction solution was heated to 45 C and then stirred vigorously for 12 hours at that temperature. The reaction solution was cooled below 10 C, and 76 g of ice was first added and 250 ml of water was then added. Thereafter, 25 ml of concentrated HCl was gradually added to maintain the resulting solution at an acidic pH>l. 200 ml of EtOAc was added to the reaction mixture which was then stirred vigorously, thereby producing white solids that were not dissolved in EtOAc. These solids were filtered and an EtOAc layer was separated. The aqueous layer was extracted once again with 100 ml of EtOAc and was combined with the previously extracted organic layer. The organic layer was washed with 150 ml of 5% NaHCO3, and was concentrated. The resulting concentrates were dissolved in 200 ml OfCH2Cl2, and were vigorously shaken to separate two layers with addition of 70 ml of an aqueous 2N NaOH solution. A CH2Cl2 layer was further separated twice with treatment of an aqueous 2N NaOH solution (70 ml x 2). The thus-separated aqueous solutions were combined together and adjusted to an acidic pH > 2, thereby forming solids. The resulting solids were filtered and separated to give Lapachol. The thus-obtained Lapachol was recrystallized from 75% EtOH. The resulting Lapachol was mixed with 80 ml of sulfuric acid, and the mixture was vigorously stirred at room temperature for 10 min and 200 g of ice was added thereto to complete the reaction. 60 ml OfCH2Cl2 was added to the reaction materials which were then shaken vigorously. Thereafter, a CH2Cl2 layer was separated and washed with 5% NaHCO3. An aqueous layer was extracted once again using 30 ml of CH2Cl2, washed with 5% NaHCO3 and combined with the previously extracted organic layer. The organic layer was dried over MgSO4 and concentrated to give impure beta- <n="53"/>Lapachone. The thus-obtained beta-Lapachone was reciystallized from isopropanol, thereby obtaining 8.37 g of pure beta-Lapachone.1H-NMR (CDCl3, S): 8.05 (IH, dd, J=I, 8Hz), 7.82 (IH, dd, J=I, 8 Hz), 7.64 (IH, dt, J=I, 8 Hz), 7.50 (IH, dt, J=I, 8 Hz), 2.57 (2H, t, J=6.5 Hz), 1.86 (2H, t, J=6.5 Hz) 1.47 (6H, s)
	With sulfuric acid; at 20℃; for 0.166667h;	17.4 g (0.10M) of 2-hydroxy-l,4-naphthoquinone was dissolved in 120 ml of DMSO, and 0.88 g (0.1 IM) of LiH was gradually added thereto. Here, this should be done with care because hydrogen evolves. The reaction solution was stirred, and after confirming no further production of hydrogen, was additionally stirred for another 30 min. Then, 15.9 g (O.IOM) of prenyl bromide (1- bromo-3-methyl-2-butene) and 3.35 g (0.025M) of LiI were gradually added thereto. The reaction solution was heated to 45 C and then stirred vigorously for 12 hours at that temperature. The reaction solution was cooled below 10C, and 76 g of ice was first added and 250 ml of water was then added. Thereafter, 25 ml of concentrated HCl was gradually added to maintain the resulting solution at an acidic pH>l. 200 ml of EtOAc was added to the reaction mixture which was then stirred vigorously, thereby producing white solids that were not dissolved in EtOAc. These solids were filtered and an EtOAc layer was separated. The aqueous layer was extracted once again with 100 ml of EtOAc and was combined with the previously extracted organic layer. The organic layer was washed with 150 ml of 5% NaHCtheta3, and was concentrated. The resulting concentrates were dissolved in 200 ml OfCH2Cl2, and were vigorously shaken to separate two layers with addition of 70 ml of an aqueous 2N NaOH solution. A CH2Cl2 layer was further separated twice with treatment of an aqueous 2N NaOH solution (70 ml x 2). The thus-separated aqueous solutions were combined together and adjusted to an acidic pH > 2, thereby forming solids. The resulting solids were filtered and separated to give Lapachol. The thus-obtained Lapachol was recrystallized from 75% EtOH. The resulting Lapachol was mixed with 80 ml of sulfuric acid, and the mixture was vigorously stirred at room temperature for 10 min and 200 g of ice was added thereto to complete the reaction. 60 ml OfCH2Cl2 was added to the reaction materials which were then shaken vigorously. Thereafter, a CH2Cl2 layer was separated and washed with 5% NaHCO3. An aqueous layer was extracted once again using 30 ml of CH2Cl2, washed with 5% NaHCO3 and combined with the previously extracted organic layer. The organic layer was dried over MgSO4 and concentrated to give impure <n="52"/>naphthoquinone compound. The thus-obtained the naphthoquinone compound was recrystallized from isopropanol, thereby obtaining 8.37 g of pure beta-Lapachone.IH-NMR (CDCD, delta): 8.05 (IH, dd, J=I, 8Hz), 7.82 (IH, dd, J=I, 8 Hz), 7.64 (IH, dt, J-I, 8 Hz), 7.50 (IH, dt, J=I, 8 Hz), 2.57 (2H, t, J=6.5 Hz), 1.86 (2H, t, J=6.5 Hz) 1.47 (6H, s)
	With sulfuric acid; at 20℃; for 0.166667h;	17.4 g (0.1 OM) of 2-hydroxy-l,4-naphthoquinone was dissolved in 120 ml of DMSO, and 0.88 g (0.1 IM) of LiH was gradually added thereto. Here, this should be done with care because hydrogen evolves. The reaction solution was stirred, and after confirming no further production of hydrogen, was additionally stirred for another 30 min. Then, 15.9 g (O.IOM) of prenyl bromide (1- bromo-3-methyl-2-butene) and 3.35 g (0.025M) of LiI were gradually added thereto. The reaction solution was heated to 45 "C and then stirred vigorously for 12 hours at that temperature. The reaction solution was cooled below 10C, and 76 g of ice was first added and 250 ml of water was then added. Thereafter, 25 ml of concentrated HCl was gradually added to maintain the resulting solution at an acidic pH>l . 200 ml of EtOAc was added to the reaction mixture which was then stirred vigorously, thereby producing white solids that were not dissolved in EtOAc. These solids <n="53"/>were filtered and an EtOAc layer was separated. The aqueous layer was extracted once again with 100 ml of EtOAc and was combined with the previously extracted organic layer. The organic layer was washed with 150 ml of 5% NaHCO3, and was concentrated. The resulting concentrates were dissolved in 200 ml OfCH2Cl2, and were vigorously shaken to separate two layers with addition of 70 ml of an aqueous 2N NaOH solution. A CH2Cl2 layer was further separated twice with treatment of an aqueous 2N NaOH solution (70 ml x 2). The thus-separated aqueous solutions were combined together and adjusted to an acidic pH > 2, thereby forming solids. The resulting solids were filtered and separated to give Lapachol. The thus-obtained Lapachol was recrystallized from 75% EtOH. The resulting Lapachol was mixed with 80 ml of sulfuric acid, and the mixture was vigorously stirred at room temperature for 10 min and 200 g of ice was added thereto to complete the reaction. 60 ml OfCH2Cl2 was added to the reaction materials which were then shaken vigorously. Thereafter, a CH2Cl2 layer was separated and washed with 5% NaHCO3. An aqueous layer was extracted once again using 30 ml of CH2Cl2, washed with 5% NaHCO3 and combined with the previously extracted organic layer. The organic layer was dried over MgSO4 and concentrated to give impure beta- Lapachone. The thus-obtained beta-Lapachone was recrystallized from isopropanol, thereby obtaining 8.37 g of pure beta-Lapachone.1H-NMR (CDCl3, delta): 8.05 (IH, dd, J=I, 8Hz), 7.82 (IH, dd, J=I, 8 Hz), 7.64 (IH, dt, J=I, 8 Hz), 7.50 (IH, dt, J=I, 8 Hz), 2.57 (2H, t, J=6.5 Hz), 1.86 (2H, t, J=6.5 Hz) 1.47 (6H, s)

Reference： [1]RSC Advances,2016,vol. 6,p. 76053 - 76063
[2]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 4143 - 4150
[3]Journal of the Brazilian Chemical Society,2015,vol. 26,p. 1013 - 1027
[4]Chemical Communications,2016,vol. 52,p. 13281 - 13284
[5]European Journal of Organic Chemistry,2017,vol. 2017,p. 3763 - 3773
[6]Patent: WO2019/50422,2019,A1 .Location in patent: Page/Page column 23
[7]Journal of Medicinal Chemistry,1984,vol. 27,p. 990 - 994
[8]Tetrahedron Letters,2014,vol. 55,p. 1475 - 1478
[9]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 668 - 674
[10]Medicinal Chemistry Research,2020
[11]Acta poloniae pharmaceutica,2001,vol. 58,p. 133 - 135
[12]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 1364 - 1373
[13]ACS Chemical Biology,2018,vol. 13,p. 1950 - 1957
[14]ChemMedChem,2015,vol. 10,p. 1413 - 1423
[15]Journal of the American Chemical Society,2017,vol. 139,p. 13200 - 13207
[16]Organic and Biomolecular Chemistry,2013,vol. 11,p. 459 - 468
[17]Gazzetta Chimica Italiana,1882,vol. 12,p. 353
[18]Gazzetta Chimica Italiana,1915,vol. 45 II,p. 56
Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti,1915,vol. <5> 24 I,p. 1062
[19]Tetrahedron Letters,1998,vol. 39,p. 8221 - 8224
[20]European Journal of Medicinal Chemistry,2004,vol. 39,p. 639 - 645
[21]Journal of the Chemical Society,1892,vol. 61,p. 638
[22]Journal of the Chemical Society,1892,vol. 61,p. 638
[23]Journal of the American Chemical Society,1936,vol. 58,p. 1190,1195
[24]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2008,vol. 47,p. 427 - 433
[25]European Journal of Medicinal Chemistry,2009,vol. 44,p. 2334 - 2337
[26]Tetrahedron Letters,2009,vol. 50,p. 1550 - 1553
[27]European Journal of Medicinal Chemistry,2011,vol. 46,p. 399 - 410
[28]Journal of the Indian Chemical Society,2010,vol. 87,p. 85 - 95
[29]European Journal of Medicinal Chemistry,2012,vol. 53,p. 264 - 274
[30]Journal of the Brazilian Chemical Society,2013,vol. 24,p. 145 - 163
[31]Rapid Communications in Mass Spectrometry,2013,vol. 27,p. 816 - 824
[32]European Journal of Medicinal Chemistry,2013,vol. 62,p. 98 - 110
[33]MedChemComm,2015,vol. 6,p. 120 - 150
[34]Chemical Communications,2015,vol. 51,p. 9141 - 9144
[35]New Journal of Chemistry,2017,vol. 41,p. 3723 - 3731
[36]Patent: WO2008/66297,2008,A1 .Location in patent: Page/Page column 50-52
[37]Patent: WO2008/66301,2008,A1 .Location in patent: Page/Page column 48-50
[38]Patent: WO2008/66299,2008,A1 .Location in patent: Page/Page column 50; 51
[39]ChemPlusChem,2019,vol. 84,p. 52 - 61

11
[ 84-79-7 ]
[ 4707-32-8 ]
[ 4707-33-9 ]

Yield	Reaction Conditions	Operation in experiment
	With boron trifluoride; In dichloromethane; at 20℃; for 4h;	General procedure: To a solution of lapachol (2) (50 mg, 0.2 mmol) in DCM (5 mL) was added the appropriate amounts of different Lewis acids. The mixture was stirred at room temperature for 4 h or 12 h and then the reaction solution was directly assessed by the HPLC analysis using a mixture of solvent methanol/water (1:3) as the mobile phase. beta-Lapachone (1): mp 159-160?C; 1H NMR (300 MHz, CDCl3) d: 8.07 (dd, J = 1.8 Hz, 1H), 7.82 (dd, J = 1.8 Hz, 1H), 7.64 (dt, J = 1.8 Hz, 1H), 7.53 (dt, J = 1.8 Hz, 1H), 2.58 (t, J = 6.6 Hz, 2H), 1.86 (t, J = 6.5 Hz, 2H), 1.47 (s, 6H). 13C NMR (75 MHz, CDCl3) delta: 179.3, 178.1, 161.5, 134.2, 132.1, 130.1, 129.7, 128.0, 123.5, 112.2, 78.7, 31.1, 26.2, 15.7. HRMS-ESI m/z [M+H]+ calculated for C15H15O3: 243.1016, found: 243.1019. alpha-lapachone (3): mp 116-118?C; 1H NMR (300 MHz, CDCl3) d: 8.06 (m, 2H), 7.68 (m, 2H), 2.62 (t, J = 6.6 Hz, 2H), 1.82 (t, J = 6.5 Hz, 2H), 1.44 (s, 6H). 13C NMR (75 MHz, CDCl3) delta: 183.9, 179.5, 154.1, 133.3, 132.4, 131.6, 130.7, 125.8, 125.5, 119.6, 77.6, 30.9, 26.0, 16.2. HRMS-ESI m/z [M+H]+ calcd for C15H15O3: 243.1016, found: 243.1013. The spectroscopic data were identical to those reported in the literature 14.
	With zirconium(IV) chloride; In dichloromethane; at 20℃; for 4h;	General procedure: To a solution of lapachol (2) (50 mg, 0.2 mmol) in DCM (5 mL) was added the appropriate amounts of different Lewis acids. The mixture was stirred at room temperature for 4 h or 12 h and then the reaction solution was directly assessed by the HPLC analysis using a mixture of solvent methanol/water (1:3) as the mobile phase. beta-Lapachone (1): mp 159-160?C; 1H NMR (300 MHz, CDCl3) d: 8.07 (dd, J = 1.8 Hz, 1H), 7.82 (dd, J = 1.8 Hz, 1H), 7.64 (dt, J = 1.8 Hz, 1H), 7.53 (dt, J = 1.8 Hz, 1H), 2.58 (t, J = 6.6 Hz, 2H), 1.86 (t, J = 6.5 Hz, 2H), 1.47 (s, 6H). 13C NMR (75 MHz, CDCl3) delta: 179.3, 178.1, 161.5, 134.2, 132.1, 130.1, 129.7, 128.0, 123.5, 112.2, 78.7, 31.1, 26.2, 15.7. HRMS-ESI m/z [M+H]+ calculated for C15H15O3: 243.1016, found: 243.1019. alpha-lapachone (3): mp 116-118?C; 1H NMR (300 MHz, CDCl3) d: 8.06 (m, 2H), 7.68 (m, 2H), 2.62 (t, J = 6.6 Hz, 2H), 1.82 (t, J = 6.5 Hz, 2H), 1.44 (s, 6H). 13C NMR (75 MHz, CDCl3) delta: 183.9, 179.5, 154.1, 133.3, 132.4, 131.6, 130.7, 125.8, 125.5, 119.6, 77.6, 30.9, 26.0, 16.2. HRMS-ESI m/z [M+H]+ calcd for C15H15O3: 243.1016, found: 243.1013. The spectroscopic data were identical to those reported in the literature 14.

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 483 - 488
[2]Journal of Medicinal Chemistry,2007,vol. 50,p. 696 - 706
[3]Gazzetta Chimica Italiana,1882,vol. 12,p. 353
[4]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1982,vol. 21,p. 251 - 252
[5]Journal of the Chemical Society,1892,vol. 61,p. 638
[6]Tetrahedron,2002,vol. 58,p. 4801 - 4807
[7]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 2621 - 2630
[8]Tetrahedron Letters,2014,vol. 55,p. 1475 - 1478
[9]Tetrahedron Letters,2014,vol. 55,p. 1475 - 1478
[10]ChemPlusChem,2019,vol. 84,p. 52 - 61
[11]ChemPlusChem,2019,vol. 84,p. 52 - 61

12
[ 67-56-1 ]
[ 4707-32-8 ]
[ 15297-92-4 ]
[ 65017-95-0 ]
[ 65017-94-9 ]
[ 74693-28-0 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1980,vol. 19,p. 13 - 16

13
[ 64-17-5 ]
[ 4707-32-8 ]
[ 15297-92-4 ]
[ 65017-95-0 ]
[ 65017-94-9 ]
[ 74693-29-1 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1980,vol. 19,p. 13 - 16

15
[ 4707-32-8 ]
[ 15297-92-4 ]
[ 65017-95-0 ]
[ 65017-94-9 ]
[ 65017-93-8 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1980,vol. 19,p. 13 - 16
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1980,vol. 19,p. 13 - 16

16
[ 4707-32-8 ]
C₁₅H₁₅O₃ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1989,vol. 111,p. 1337 - 1343

17
[ 17241-45-1 ]
[ 4707-32-8 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1982,vol. 21,p. 251 - 252

18
[ 146176-51-4 ]
[ 4707-32-8 ]
N-[2,2-Dimethyl-5-oxo-3,4-dihydro-2H,5H-benzo[h]chromen-(6Z)-ylidene]-acetamide [ No CAS ]
N-(5-Hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromen-6-yl)-acetamide [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1992,vol. 29,p. 1457 - 1460

19
[ 148839-52-5 ]
[ 4707-32-8 ]

Reference： [1]Tetrahedron Letters,1993,vol. 34,p. 2437 - 2440

20
[ 186581-53-3 ]
[ 4707-32-8 ]
[ 64184-03-8 ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6171 - 6173
[2]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 5459 - 5466

21
[ 4707-32-8 ]
[ 78-90-0 ]
5,6-dihydro-2,7,7-trimethyl-7H-pyrano[3',2':4]naphtha[1,2-b]pyrazine [ No CAS ]
5,6-dihydro-3,7,7-trimethyl-7H-pyrano[3',2':4]naphtha[1,2-b]pyrazine [ No CAS ]

Reference： [1]Synthetic Communications,2007,vol. 37,p. 113 - 118
[2]Synthetic Communications,2007,vol. 37,p. 113 - 118
[3]Journal of the Indian Chemical Society,2010,vol. 87,p. 85 - 95

22
[ 4707-32-8 ]
6-diazo-2,2-dimethyl-2,3,4,6-tetrahydrobenzo[h]chromen-5-one [ No CAS ]

Reference： [1]Magnetic Resonance in Chemistry,2006,vol. 44,p. 481 - 490

23
[ 4707-32-8 ]
[ 108-24-7 ]
[ 876062-69-0 ]

Yield	Reaction Conditions	Operation in experiment
38%		To a mixture of zinc dust (50.0 g, 0.765 mol) and <strong>[4707-32-8]2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione</strong> (50.0 g, 0.206 mol) is added DMF (500 mL). The mixture is allowed to stir for 15 min. To the reaction is then added a mixture of N-(tert-butoxycarbonyl) glycine (43.38 g, 0.247 mol) and HBTU (156.5 g, 0.413 mol) in 5 small portions over a period of 3 hours to control the exothermic reaction. The reaction was stirred for 16 hours. Ethyl acetate (EtOAc) (1300 mL) is then added, and the reaction is filtered through celite. The celite is bed washed with EtOAc (200 mL). The combined EtOAc solutions are washed with water (2×1000 mL) followed by saturated NaCl (500 mL). The organic layer is dried over sodium sulfate and concentrated under reduced pressure. The crude residue (103 g) is dissolved in acetic anhydride (150 mL) followed by the addition of zinc dust (13.5 g, 0.206 mol) and triethylamine (25.9 mL, 0.186 mol). The reaction is stirred for 1.15 hours. The solvent (acetic anhydride and triethylamine) is removed under reduced pressure to yield a residue. The residue was dissolved in EtOAc (1000 mL) and washed with water (2×500 mL), 5% sodium bicarbonate (2×500 mL) saturated NaCl (500 mL) and dried over Na2SO4. Concentration of the ethyl acetate solution under reduced pressure yields a yellowish white crude product (103 g) that is purified by crystallization from hexane-ethyl acetate. For crystallization, the crude product is dissolved in refluxing EtOAc (200 mL) and hexane (300 mL) is added. The mixture is allowed to cool to room temperature and stirred for 14 hr. A solid separated out which is collected by filtration and washed with 5% EtOAc in hexane (500 mL). The desired product (38.2 g) is obtained 98% pure with 2% of bis-glycine as a side-product. The 98% pure product (38.2 g) is again crystallized from refluxing EtOAc (165 mL) and hexanes (250 mL). The hot solution is allowed to cool to room temperature and stirred for 15 hr. The white solid obtained is filtered, washed with 5% EtOAc in hexane (400 mL), and dried under high vacuum at 45-50 C. The desired product (34.6 g, 38%) is obtained as a white solid at 99.83% purity based upon HPLC analysis. The 1H NMR is the same as described in Example 5a.
31%		A mixture of zinc dust (6.0 g, 91.7 mmol), <strong>[4707-32-8]2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione</strong> (6.0 g, 24.8 mmol), Na2S2O4 (17.26 g, 99.1 mmol), N-(tert-butoxycarbonyl)glycine (8.77 g, 49.6 mmol), triethylamine (3.1 ml, 22.3 mmol), HBTU (18.79 g, 49.6 mmol), and DMF (100 ml) is stirred for 16 hours at room temperature. To the reaction mixture is then added ethyl acetate (300 ml). The reaction is filtered and the filtrate washed with H2O (4×200 ml). The organic extract is dried with Na2SO4, and concentrated under reduced pressure to yield a residue. The residue is dissolved in acetic anhydride (30 ml), zinc dust (3.0 g, 45.9 mmol) and triethylamine (3.35 ml, 24.0 mmol) are then added. The mixture is heated to 90 C. with vigorous stirring and held at 90 C. for 2 hours, after which it is allowed to cool and the solvent is removed under reduced pressure to yield a second residue. The second residue is dissolved in ethyl acetate (200 ml) and washed with water (2×100 ml). The organic extract is dried with Na2SO4 and concentrated under reduced pressure to yield unrefined product. The unrefined product is purified by flash column chromatography on silica, eluting with 2% ethyl acetate in dichloromethane, to afford product about 60% pure. The product is further purified by crystallization from ethyl acetate/hexane, which gives the desired product as pure white solid (3.2 g, 31%). M.p.=177 C.; 400 MHz 1H NMR (CDCl3) delta: 8.21 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.46 (m, 2H), 5.13 (br. s, 1H), 4.30 (d, J=5.6 Hz, 2H), 2.68 (t, J=6.6 Hz, 2H), 2.38 (s, 3H), 1.87 (t, J=6.6 Hz, 2H), 1.48 (s, 9H), 1.42 (s, 6H); LCMS: 444 [M+H]; Calc. for C24H29NO7: C, 64.94; H, 6.59; N, 3.16; Found C, 64.98; H, 6.51; N, 3.15.

Reference： [1]Patent: US2006/34796,2006,A1 .Location in patent: Page/Page column 42
[2]Patent: US2006/34796,2006,A1 .Location in patent: Page/Page column 42

24
[ 4707-32-8 ]
[ 56-81-5 ]
[ 876062-71-4 ]

Yield	Reaction Conditions	Operation in experiment
36%	With toluene-4-sulfonic acid; In benzene; for 6h;Heating / reflux;Product distribution / selectivity;	To a solution of <strong>[4707-32-8]2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione</strong> (1.21 g, 5 mmol) in benzene (12 ml) is added glycerol (0.92 g, 10 mmol) and p-toluenesulfonic acid monohydrate (0.28 g, 1.5 mmol). The resulting mixture is refluxed for 6 hours. After removal of the solvent, product is purified by column chromatography on silica gel eluting with 30% ethyl acetate in methylene chloride to provide 0.57 g (36% yield) as a light yellow solid, which is a mixture of diasteromers. M.p. 44-46 C.; 400 MHz 1H NMR (CDCl3) delta: 1.41 (s, 6H), 1.73-1.82 (m, 2H), 2.36-2.42 (m, 1H), 2.48-2.54 (m, 1H), 3.72-3.78 (m, 1H), 4.18 (d, J=2.5 Hz, 1H), 4.20-4.29 (m, 1H), 4.40 (t, J=8.0 Hz, 1H), 4.71-4.74 (m, 1H), 4.85 (d, J=8.8 Hz, 1H), 7.38-7.44 (m, 2H), 7.54-7.56 (m, 1H), 7.75-7.78 (m, 1H); LCMS: Calc. for C18H21O5: 217; Found 217.

Reference： [1]Patent: US2006/34796,2006,A1 .Location in patent: Page/Page column 45

25
[ 4707-32-8 ]
C₁₅H₁₅NO₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 696 - 706

26
lapachol-1,4-di-O-β-D-glucopyranoside [ No CAS ]
[ 492-61-5 ]
[ 4707-32-8 ]
[ 4707-33-9 ]

Reference： [1]Journal of Natural Products,2007,vol. 70,p. 567 - 570

27
[ 4707-32-8 ]
[ 78-93-3 ]
E-2,2-dimethyl-6-(1-methyl-2-oxo-propylidene)-2,3,4,6-tetrahydro-benzo[h]chromen-5-one [ No CAS ]
2,2,7-trimethyl-3,4-dihydrobenzo[h]cyclopenta[f]chromen-6(2H)-one [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6171 - 6173

28
[ 765-43-5 ]
[ 4707-32-8 ]
C₂₀H₂₀O₃ [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6171 - 6173

29
[ 4707-32-8 ]
[ 67-64-1 ]
E-2,2-dimethyl-6-(2-oxo-propylidene)-2,3,4,6-tetrahydro-benzo[h]chromen-5-one [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6171 - 6173

30
[ 4707-32-8 ]
[ 141-97-9 ]
E-4-(2,2-dimethyl-5-oxo-3,4-dihydro-2H,5H-benzo[h]chromen-6-ylidene)-3-oxo-butyric acid ethyl ester [ No CAS ]
Z-2-(2,2-dimethyl-5-oxo-3,4-dihydro-2H,5H-benzo[h]chromen-6-ylidene)-3-oxo-butyric acid ethyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6171 - 6173

31
[ 4707-32-8 ]
2,2-dimethyl-3,4-dihydro-2H-benzo[f]pyrano[2,3-h]chromen-6-one [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2002,p. 1455 - 1460

32
[ 4707-32-8 ]
3-bromo-4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[f]pyrano[2,3-h]chromen-6-one [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2002,p. 1455 - 1460

33
[ 4707-32-8 ]
7-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[f]pyrano[2,3-h]chromen-6-one [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2002,p. 1455 - 1460

34
[ 4707-32-8 ]
[ 476213-11-3 ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2002,p. 1455 - 1460

35
[ 4707-32-8 ]
ethyl 3-bromo-4-hydroxy-2,2-dimethyl-6-oxo-3,4-dihydro-2H,6H-benzo[f]pyrano[2,3-h]chromene-8-carboxylate [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2002,p. 1455 - 1460

36
[ 4707-32-8 ]
acetic acid 2-(6,6-dimethyl-5,6-dihydro-4H-3,7-dioxa-1-aza-cyclopenta[l]phenanthren-2-yl)-phenyl ester [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2000,vol. 50,p. 1120 - 1128

37
[ 83-72-7 ]
bis-<13-((R)-cyclopentene (2)-yl)-tridecanoyl>-peroxide [ No CAS ]
[ 4707-32-8 ]

Reference： [1]Tetrahedron Letters,1998,vol. 39,p. 8221 - 8224

38
[ 870-63-3 ]
silver-salt of 4-isopropyl-tropolone [ No CAS ]
[ 4707-32-8 ]

Reference： [1]Tetrahedron Letters,1998,vol. 39,p. 8221 - 8224

39
[ 53444-18-1 ]
[ 4707-32-8 ]

Reference： [1]Journal of the American Chemical Society,1936,vol. 58,p. 1190,1195

40
[ 4707-32-8 ]
[ 1530-34-3 ]
[ 1012069-35-0 ]

Reference： [1]Synlett,2007,p. 3123 - 3126

41
[ 4707-32-8 ]
[ 41273-34-1 ]
[ 1012069-36-1 ]

Reference： [1]Synlett,2007,p. 3123 - 3126

42
[ 452-58-4 ]
[ 4707-32-8 ]
[ 1110624-30-0 ]
[ 1110624-33-3 ]

Yield	Reaction Conditions	Operation in experiment
45%; 39%	With triton X-100; In water; at 80℃; for 2h;Green chemistry;	General procedure: A mixture of beta-lapachone 2 (1.0 mmol), 2,3-diaminopyridine (1.0 mmol), triton X-100 (15 mol%), and distilled water (5.0 ml) were taken in a round-bottom flask. The reaction mixture was allowed to stir magnetically at 80 C for 2 h. Progress of the reaction was monitored by TLC. After completion of the reaction, the crude mass was obtained. The residue was purified over a column of silica gel (100-200 mesh) eluting with a mixture of hexane and ethyl acetate in different ratio, to yield regioisomers (4a and 4b). Characterization data for compounds: 6,7-dihydro-8,8-dimethyl-8H-pyrano[3',2':4]naphtha[1,2-e]pyrido[2,3-b]pyrazine (4a) Bright yellow needles; mp 210-212 C[17]; IR (KBr cm1): 3150-2960, 1625, 1600, 1540 (C=N); 1H NMR (300 MHz; CDCl3; Me4Si): delta 1.54 (6H, S, 2 Me), 2.06 (2H, t, J 6.57 Hz,CH2), 3.31 (2H, t, J 6.57 Hz, CH2), 7.73 (1H, dd, J 8.43, 4.02 Hz, 1 Ar-H), 7.80 (2H, m, 2 Ar-H), 8.31-8.34 (1H, m, 1 Ar-H), 8.57 (1H, dd, J 8.43, 1.83 Hz, 1 Ar-H), 9.21 (1H, dd, J 1.83, 4.02 Hz, 1 Ar-H) and 9.48-9.51 (1H, m, 1 Ar-H). 13C NMR (75.45 MHz; CDCl3; DEPT, Me4Si): 26.7 (C-CH3), 26.7 (C-CH3), 18.2 (CH2), 32.30 (CH2), 76.6 (C8), 109.23 (C5b), 124.59-128.09 (aromatic C), 129.71 (C9b), 130.47 (aromatic C), 137.72 (aromatic C), 147.5 (C9a), 142.25 (C14a), 145.59 (C5a), 152.65 (aromatic C); FAB MS (m/z): 316 (100) [MH], 300 [M-Me], 260, 120, 107; Anal C20H17N3O. Cald For: C, 76.19; H, 5.39; N, 13.33. Found: C, 76.09; H, 5.31; N, 13.25. 6,7-Dihydro-8,8-dimethyl-8H-pyrano[3',2':4]naphtha[2,1-e]pyrido[2,3-b]pyrazine (4b) Bright orange needles; mp 202-205 C [17]; IR (KBr cm1): 3140-2975, 1600, 1625, 1550 (C=N), 1400; 1H NMR (300 MHz; CDCl3; Me4Si): delta 1.54 (6H, s, 2 Me), 2.09 (2H, t, J 6.60 Hz,CH2), 3.41 (2H, t, J 6.60 Hz, CH2), 7.69 (1H, dd, J 8.40, 4.20 Hz, 1 Ar-H), 7.79 (2H, m, 2 Ar-H), 8.32-8.35 (1H, m, 1 Ar-H), 8.64 (1H, dd, J 8.43, 1.83 Hz, 1 Ar-H), 9.22 (1H, dd, J 4.20, 2.01 Hz, 1 Ar-H) and 9.27-9.30 (1H, m, 1 Ar-H). 13C NMR (75.45 MHz; CDCl3; DEPT, Me4Si): 26.8 (C-CH3), 26.7 (C-CH3), 18.2 (CH2), 32.32 (CH2), 76.6 (C8), 109.23 (C5b), 122.47-148 (aromatic C), 153 (C2), 153.98 (C14a); FAB MS (m/z): [MH]316 (100), 300 [M-Me], 260, 120, 107; Anal C20H17N3O. Cald For: C, 76.19; H, 5.39; N, 13.33. Found: C, 76.01; H, 5.35; N, 13.03.

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2008,vol. 47,p. 427 - 433
[2]Synthetic Communications,2017,vol. 47,p. 688 - 694
[3]Journal of the Indian Chemical Society,2010,vol. 87,p. 85 - 95

43
[ 16009-56-6 ]
[ 4707-32-8 ]
[ReCl3(β-lapachone)(PPh3)] [ No CAS ]

Reference： [1]Inorganica Chimica Acta,2007,vol. 360,p. 2192 - 2196

44
[ 4707-32-8 ]
[ 15297-93-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In tetrachloromethane; for 72h;Heating / reflux;	Example 11 : Synthesis of Compound 11; 1.21 g (50 mM) of beta-Lapachone (Compound 1) and 1.14 g (50 mM) of DDQ (2,3- dichloro-5,6-dicyano-l,4-benzoqinone) were dissolved in 50 ml of carbon tetrachloride and refluxed for 72 hours. The reaction solution was concentrated by distillation under reduced pressure and was Ihen purified by chromatography on silica gel to give 1.18 g of pure Compound 11.1H-NMR (CDCl3, delta): 8.08 (IH, dd, J=I.2, 7.6Hz), 7.85 (IH, dd, J=0.8, 7.6Hz), 7.68 (IH, dt, J-1.2, 7.6Hz), 7.55 (IH, dt, J=1.2, 7.6Hz), 6.63 (IH, d, J=10.0Hz), 5.56 (IH, d, J=IOOHz), 1.57 (6H, s)
	With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In tetrachloromethane; for 72h;Heating / reflux;	1.21 g (50 niM) of beta-Lapachone (Compound 1) and 1.14 g (50 mM) of DDQ (2,3- dichloro-5,6-dicyano-l,4-ben2xx[inone) were dissolved in 50 ml of carbon tetrachloride and refluxed for 72 hours. The reaction solution was concentrated by distillation under reduced pressure and was then purified by chromatography on silica gel to give 1.18 g of pure Compound 11.1H-NMR (CDCl3, delta): 8.08 (IH, dd, J=1.2, 7.6Hz), 7.85 (IH, dd, J=0.8, 7.6Hz), 7.68 (IH, dt, J=1.2, 7.6Hz), 7.55 (IH, dt, J=1.2, 7.6Hz), 6.63 (IH, d, J=10.0Hz), 5.56 (IH, d, MO.OHz), 1.57 (6H, s)

Reference： [1]Patent: WO2008/66297,2008,A1 .Location in patent: Page/Page column 58
[2]Patent: WO2008/66299,2008,A1 .Location in patent: Page/Page column 58

45
[ 4707-32-8 ]
[ 1040247-64-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 5635 - 5643

46
[ 4707-32-8 ]
[ 1075160-04-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium disulfite; In water; at 20℃; for 22.5h;pH 5;Aqueous acetate buffer;Product distribution / selectivity;	beta-lapachone with Na2S2O5 or NaHSO3 in acetate buffer 600 mg of beta-lapachone was added to 40 mL of 40 mM sodium acetate buffer at pH 5 containing 15 mg/mL Na2S2O5 or NaHSO3. The solution was mixed for 22.5 hours at room temperature, and filtered through a 0.45 mum PVDF filter.
	With sodium hydrogensulfite; In water; at 20℃; for 22.5h;water;Product distribution / selectivity;	600 mg of beta-lapachone was added to 40 mL of 5% (wt/vol) HP beta-CD (hydroxypropyl beta- cyclodextrin) containing 15 mg/mL Na2S2O5 or NaHSO3. The solution was mixed for 22.5 hours at room temperature and filtered through a 0.45 mum PVDF filter.
	With mannitol; sodium hydrogensulfite; In water; at 20℃; for 18h;water;Product distribution / selectivity;	750 mg of beta-lapachone was added to 50 mL of an aqueous solution containing 20 mg/mL Na2S2O5 and 5% mannitol. The solution was mixed for 18 hours at room temperature, and filtered through a 0.45 mum PVDF filter and lyophilized. The lyophilized solid can be reconstituted with water or 5% dextrose.

	With sodium hydrogensulfite; In water; at 20℃; for 18h;Product distribution / selectivity;	To an aqueous solution (5 mL) of sodium bisulfite (0.1012 g, 0.97 mmol) was added 2,2- dimethyl-2,3-dihydro-2H-benzo(lambda)chromene-5,6-dione (0.1031 g, 0.43 mmol). The reaction mixture was stirred at room temperature until all 2,2-dimethyl-2,3-dihydro-2H-benzo(A)chromene-5,6-dione had dissolved. The reaction mixture was lyophilized and the desired product was obtained as a yellowish orange solid. LCMS: m/z = 323 (ESI-); To an aqueous solution (5 mL) of sodium bisulfite (0.019 g, 0.018 mmol) was added 2,2- dimethyl-2,3-dihydro-2H-benzo(lambda)chromene-5,6-dione (0.0424 g, 0.18 mmol). The reaction mixture was stirred at room temperature for 18 hours and filtered. The desired product was formed and stored as an aqueous solution. For NMR studies, the reaction was carried out in D2O. LCMS: m/z = 323 (ESI-). ID NMR: [300 MHz 1H NMR (D2O); 75 MHz 13C NMR (D2O)] see Table C and D; Figure 2B.
	With sodium hydrogensulfite; In water; at 20℃; for 22.5h;pH 5;Aqueous acetate buffer;Product distribution / selectivity;	beta-lapachone with Na2S2O5 or NaHSO3 in acetate buffer 600 mg of beta-lapachone was added to 40 mL of 40 mM sodium acetate buffer at pH 5 containing 15 mg/mL Na2S2O5 or NaHSO3. The solution was mixed for 22.5 hours at room temperature, and filtered through a 0.45 mum PVDF filter.
	With sodium hydrogensulfite; In water-d2;Product distribution / selectivity;	To an aqueous solution (5 mL) of sodium bisulfite (0.019 g, 0.018 mmol) was added 2,2- dimethyl-2,3-dihydro-2H-benzo(lambda)chromene-5,6-dione (0.0424 g, 0.18 mmol). The reaction mixture was stirred at room temperature for 18 hours and filtered. The desired product was formed and stored as an aqueous solution. For NMR studies, the reaction was carried out in D2O. LCMS: m/z = 323 (ESI-). ID NMR: [300 MHz 1H NMR (D2O); 75 MHz 13C NMR (D2O)] see Table C and D; Figure 2B.
	With sodium disulfite; In water; at 20℃; for 22.5h;water;Product distribution / selectivity;	600 mg of beta-lapachone was added to 40 mL of 5% (wt/vol) HP beta-CD (hydroxypropyl beta- cyclodextrin) containing 15 mg/mL Na2S2O5 or NaHSO3. The solution was mixed for 22.5 hours at room temperature and filtered through a 0.45 mum PVDF filter.
	With sodium disulfite; mannitol; In water; at 20℃; for 18h;water;Product distribution / selectivity;	750 mg of beta-lapachone was added to 50 mL of an aqueous solution containing 20 mg/mL Na2S2O5 and 5% mannitol. The solution was mixed for 18 hours at room temperature, and filtered through a 0.45 mum PVDF filter and lyophilized. The lyophilized solid can be reconstituted with water or 5% dextrose.
	With sodium disulfite; In water; acetonitrile;Product distribution / selectivity;	To a solution of 2,2-dimemyl-2,3-dihydro-2H-benzo(lambda)chromene-5,6-dione (0.217 g, 0.9 mmol) in acetonitrile (5 mL) was added an aqueous solution (5 mL) of sodium metabisulfite (0.34 g, 1.8 mmol). The reaction mixture was mixed and lyophilized. The desired product was obtained as a yellowish orange solid. LCMS: m/z=323 (ESI-). ID and 2D NMR [300 MHz 1H NMR (DMSO-dbeta), 75 MHz 13C NMR (DMSOd6)] see Table A and B, Figure 2B.
	With sodium disulfite; In water; at 20℃; for 18h;Product distribution / selectivity;	To an aqueous solution (100 mL) of sodium metabisulfite (2.01 g, 10.5 mmol) was added 2,2- dimethyl-2,3-dihydro-2H-benzo(lambda)chromene-5,6-dione (1.503 g, 6.2 mmol). The reaction mixture was stirred at room temperature for 18 hours and then stored at 4 0C for 72 hours. Yellow crystals of the desired product separated out. The supernatant was filtered, and the isolated crystals were dried. The crystals were subjected to single crystal X-ray diffraction. The results are shown in Figure 2A. In the crystal lattice, Compound 1 is present as a dimer with two sodium molecules and 8 molecules of water; To an aqueous solution (3 mL) of sodium metabisulfite (0.045 g, 0.21 mmol) was added 2,2- dimethyl-2,3-dihydro-2//-benzo(lambda)chromene-5,6-dione (0.045 g, 0.19 mmol). The reaction mixture was stirred at room temperature for 18 hours and filtered. The desired product was formed and stored as an aqueous solution.
	With sodium disulfite; In water-d2;Product distribution / selectivity;	To an aqueous solution (3 mL) of sodium metabisulfite (0.045 g, 0.21 mmol) was added 2,2- dimethyl-2,3-dihydro-2//-benzo(lambda)chromene-5,6-dione (0.045 g, 0.19 mmol). The reaction mixture was stirred at room temperature for 18 hours and filtered. The desired product was formed and stored as an aqueous solution. For NMR studies, the reaction was carried out in D2O. LCMS: m/z = 323 (ESI-). ID NMR: [300 MHz 1H NMR (D2O); 75 MHz 13C NMR (D2O)] see Table C and D; Figure 2B.
	With sodium dithionite; In water; at 20℃; for 18h;Product distribution / selectivity;	To an aqueous solution (3 mL) of sodium dithionite (0.116 g, 0.67 mmol) was added 2,2- dimethyl-2,3-dihydro-2H-benzo(A)chromene-5,6-dione (0.0349 g, 0.14 mmol). The reaction mixture was stirred at room temperature for 18 hours and filtered. The desired product was formed and stored as an aqueous solution. For NMR studies, the reaction was carried out in D2O. LCMS: m/z = 323

Reference： [1]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 18
[2]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 18
[3]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 18
[4]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 20
[5]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 18
[6]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 20
[7]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 18
[8]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 18
[9]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 19
[10]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 18-20
[11]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 19
[12]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 20-21

47
[ 1075160-04-1 ]
[ 4707-32-8 ]

Yield	Reaction Conditions	Operation in experiment
	In water;pH 6.8 - 7;Aqueous phosphate buffer;Product distribution / selectivity;	The hydroxy sulfonate of beta-lapachone easily reverts back to beta-lapachone in dilute solutions of bisulfite and other reagents. For example when a solution of Compound 1 is diluted with a mobile phase containing acetonitrile and phosphate buffer at pH 6.8 and analyzed by HPLC, only the beta- lapachone can be detected. When a solution of Compound 1 is diluted in phosphate buffered saline at pH 7 or human plasma, the UV-vis spectrum become identical to that for a solution of beta-lapachone. <n="24"/>The pH dependence of the conversion of Compound 1 to beta-lapachone is demonstrated by the fact that the maximum concentrations of beta- lapachone that can be converted to Compound 1 decrease with increasing pH as presented in Table E.

Reference： [1]Patent: WO2008/134088,2008,A1 .Location in patent: Page/Page column 21-22

48
[ 4707-32-8 ]
[ 1027802-08-9 ]

Reference： [1]Synlett,2008,p. 2625 - 2628

49
[ 84-79-7 ]
[ 4707-32-8 ]
[ 15297-92-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5387 - 5390

50
[ 106-31-0 ]
[ 4707-32-8 ]
[ 1151806-15-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium acetate; zinc; at 110℃; for 1h;	12.0 g of <strong>[4707-32-8]2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione</strong>, 16.1 g of zinc powder, 80 mL of anhydrous butanoic acid, and 2.0 g of sodium acetate were mixed and vigorously stirred at 110 for 1 hour. The reaction mixture was cooled to room temperature and filtered. The filtered solid was washed once with 200 mL of EtOAc. The filtrate was distilled under reduced pressure to remove anhydrous butanoic acid and EtOAc. The residue was dissolved in 200 mL of CH2Cl2 and washed with water. The organic extract was dried over Na9SO4 and concentrated under reduced pressure. The residue was purified using silica gel to afford 17.6 g (yield: 92%) of the title compound as a high-viscosity transparent liquid compound. 1H-NMR (CDCl3, delta): 8.22 (dd, 1H, J=7.6, 1.5 Hz), 7.67 (dd, 1H, J=7.8, 1.5 Hz), 7.42-7.50 (m, 2H), 2.68 (t, 4H, J=7.3 Hz), 2.60 (1,2H, J=7.4 Hz), 1.78-1.92 (m, 4H), 1.83 (t, 2H, J=7.4 Hz), 1.44 (s, 6H), 1.11 (t, 3H, J=7.4 Hz), 1.09 (t, 3H, J=7.4 Hz).

Reference： [1]Patent: US2009/124680,2009,A1 .Location in patent: Page/Page column 16

51
[ 4707-32-8 ]
[ 123-62-6 ]
[ 1151806-12-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium acetate; zinc; at 110℃; for 1h;	12.0 g of <strong>[4707-32-8]2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione</strong>, 16.1 g of zinc powder, 70 mL of anhydrous propionic acid, and 2.0 g of sodium acetate were mixed and vigorously stirred at 110 for 1 hour. The reaction mixture was cooled to room temperature and filtered. The filtered solid was washed once with 200 mL of EtOAc. The filtrate was distilled under reduced pressure to remove anhydrous propionic acid and EtOAc. The residue was dissolved in 200 mL of CH2Cl2 and washed with water. The organic extract was dried over Na2SO4 and concentrated under reduced pressure. The residue was recrystallized from 200 mL of isopropanol, such that the unpurified final product reached a purity of 99% or higher. 12.2 g (yield: 86%) of the title compound was obtained as a pure white solid crystal. 1H-NMR (CDCl3, delta): 8.22 (dd, 1H, J=7.6, 1.5 Hz), 7.67 (dd, 1H, J=7.8, 1.5 Hz), 7.42-7.50 (m, 2H), 2.72 (q, 2H, J=7.6 Hz), 2.68 (t, 1H, 6.7 Hz), 2.64 (q, 1H, J=7.6 Hz), 1.88 (t, 1H, J=6.7 Hz), 1.43 (s, 6H), 1.37 (t, 3H, J=7.6 Hz), 1.33 (t, 3H, J=7.6 Hz).

Reference： [1]Patent: US2009/124680,2009,A1 .Location in patent: Page/Page column 15

52
[ 13139-16-7 ]
[ 4707-32-8 ]
C₂₆H₃₅NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium dithionite; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; zinc; In N,N-dimethyl-formamide; at 20℃; for 15h;	5 g of zinc powder, 5 g of <strong>[4707-32-8]2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione</strong>, 16.5 g of Na2S2O4, 8.1 g of N-(t-butoxycarbonyl)isoleucine, 2.8 mL of triethylamine, 17.5 g of HBTU, and 100 mL of DMF were mixed and stirred at room temperature for 15 hours. 300 mL of EtOAc was added to the reaction mixture. The reaction mixture was filtered and washed with water. The organic extract was dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was dissolved in 40 mL of acetic anhydride, and 4.0 g of zinc powder and 4.53 g of triethylamine were added thereto. The reaction mixture was heated with vigorous stirring at 85 for 2 hours and then cooled. The solvent was removed under reduced pressure. The resulting residue was dissolved in 200 mL of EtOAc and washed with water. The organic extract was dried over Na2SO4 and concentrated under reduced pressure. The unpurified product was purified by column chromatography (EtOAc/hexane), such that the final product reached a purity of 60%. 4.1 g (yield: 33%) of the title compound was obtained as a partially pure white solid crystal.

Reference： [1]Patent: US2009/124680,2009,A1 .Location in patent: Page/Page column 12-13

53
[ 4707-32-8 ]
[ 1143502-33-3 ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 1550 - 1553

54
[ 4707-32-8 ]
[ 20331-67-3 ]
[ 18865-37-7 ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 1550 - 1553
[2]ChemMedChem,2015,vol. 10,p. 1413 - 1423

55
[ 50-00-0 ]
[ 83-72-7 ]
[ 115-11-7 ]
[ 4707-32-8 ]

Reference： [1]Organic Preparations and Procedures International,2009,vol. 41,p. 211 - 215

56
[ 50-00-0 ]
[ 83-72-7 ]
[ 115-11-7 ]
[ 4707-32-8 ]
[ 4707-33-9 ]

Reference： [1]Organic Preparations and Procedures International,2009,vol. 41,p. 211 - 215

57
[ 4707-32-8 ]
3,4-dibromo-β-lapachone [ No CAS ]

Reference： [1]Journal of the Brazilian Chemical Society,2015,vol. 26,p. 1013 - 1027
[2]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3224 - 3230
[3]European Journal of Medicinal Chemistry,2011,vol. 46,p. 399 - 410
[4]MedChemComm,2016,vol. 7,p. 1555 - 1563

58
[ 137492-06-9 ]
[ 4707-32-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2010,vol. 8,p. 3790 - 3795

59
[ 4707-32-8 ]
[ 1253830-87-3 ]
1,2,16,17-tetrahydro-3,3,15,15-tetrameethyl-3H,15H-dibenzo[ch]dipyran[b',2,1-b',8,9]phenazine [ No CAS ]
1,2,10,11-tetrahydro-3,3,12,12-tetramethyl-3H,12H-dibenzo[cj]dipyran[b',2,1-b',7,6]phenazine [ No CAS ]

Reference： [1]Synlett,2010,p. 1931 - 1934

60
[ 84-79-7 ]
[ 4707-32-8 ]
[ 15297-92-4 ]
[ 4707-33-9 ]
[ 74693-31-5 ]
[ 18635-24-0 ]