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CAS No. : | 130-16-5 | MDL No. : | MFCD00006788 |
Formula : | C9H6ClNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CTQMJYWDVABFRZ-UHFFFAOYSA-N |
M.W : | 179.60 | Pubchem ID : | 2817 |
Synonyms : |
5-Chloro-8-quinolinol;Dermofungin;NSC35083;Cloxyquin
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 48.78 |
TPSA : | 33.12 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.35 cm/s |
Log Po/w (iLOGP) : | 1.94 |
Log Po/w (XLOGP3) : | 2.88 |
Log Po/w (WLOGP) : | 2.59 |
Log Po/w (MLOGP) : | 1.76 |
Log Po/w (SILICOS-IT) : | 2.6 |
Consensus Log Po/w : | 2.35 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.38 |
Solubility : | 0.0741 mg/ml ; 0.000412 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.24 |
Solubility : | 0.104 mg/ml ; 0.000582 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.74 |
Solubility : | 0.0327 mg/ml ; 0.000182 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.34 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With hydrogenchloride In water at 111℃; for 24 h; | General procedure: A 1N HCl solution (82.5 mL) was added to the aniline (~1 mmol) in a round bottom flask. To this was added acrolein diethyl acetal (2.5 mmol). The resulting solution was refluxed at 111 °C for 24 hours. After cooling to room temperature, the solution was neutralized (pH 7−8) by addition of solid Na2CO3. The product was then extracted into dichloromethane (3 x 100 mL), and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The crude residue was then purified by column chromatography (elution mixture of hexane with ethyl acetate or 15percent ethyl acetate/cyclohexane with methanol) to give the desired quinoline product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine In ethanol for 12h; Reflux; | |
68% | In ethanol at 80℃; for 24h; | 5-chloro-7-(morpholinomethyl)quinolin-8-ol (23) In a carousel reaction tube, 0.40 g (2.23 mmol) of 5-chloroquinolin-8-ol was mixed with 300 μL formaldehyde in 20 mL dry ethanol. To this solution was added 260 μL morpholine (2.4 mmol). The mixture was refluxed at 80C for 24 hr. The precipitate was filtered. The crude product was purified by recrystallization from 1:1 EtOH-H2O to yield the final product (0.42 g, 68%); mp 89-91 oC; FT-IR (cm-1):1494.45, 1453.19, 1405.94, 1369.28; 1H NMR (300 MHz, DMSO-d6, ppm): 2.44-2.49 (m, 4H), 3.56-3.63(m, 4H), 3.71 (t, J = 2.51Hz, 2H), 7.64 (t, J = 2.48Hz, 1H), 7.66-7.71 (m, 1H), 8.44-8.49 (m, 1H), 8.91-8.95(m, 1H); 13C NMR (75 MHz, DMSO-d6, ppm): 53.1, 56.0, 66.2, 118.2, 120.3, 122.6, 124.9, 128.5, 132.3,138.8, 148.9, 150.8; Anal. HPLC (Rt: 3.692 min; Height: 343.34 mAU; Area%: >99%). |
67.6% | In ethanol at 80℃; for 24h; |
65% | In ethanol for 8h; Reflux; Inert atmosphere; | General Procedure for the Synthesis of Compounds 4a-m, 5a-d, 6a, and 6b General procedure: To a stirred solution of 5-chloroquinolin-8-ol (2, 360 mg, 2.0 mmol) in dry EtOH (10 mL) was added appropriate amines (2.2 mmol) and paraformaldehyde (240 mg, 8.0 mmol). The reaction mixturewas heated to reflux for 8 h under nitrogen atmosphere. After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and then kept in ice-bath for 3 h. The product was precipitated from the reaction mixture. The desired product was filtered off, washed with cold EtOH (3 mL) and dried under vacuum overnight. |
With ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; 1,1,2,2-tetrachloroethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate In N,N-dimethyl-formamide at 5 - 20℃; for 7h; | Synthesis and analysis of cloxyquin analogues which were analyzed in detail in this study. General procedure: Cloxyquin (500 mg, 2.784 mmol) was dissolved in N,N-dimethylformamide (10 mL) and to the solution, K2CO3 (1.15 g, 8.352 mmol for A2764; 770 mg, 5.568 mmol for A2793) was added. The reaction mixture was cooled to 5 °C, then the appropriate alkylating reagent (4.176 mmol), N-2-chloroethyl-N,N-diethylamine hydrochloride (for A2764) or ethyl bromoacetate (for A2793), was added. The resulting mixture was strirred at 50 °C overnight (for A2793) or at room temperature for 7 hours (for A2764), while monitoring tlc. Then, the reaction mixture was concentrated under reduced pressure, and to the residue water was added (20 mL). It was extracted with ethyl acetate (3×20 mL). The organic phase was dried over MgSO4 and the solvent was evaporated under reduced pressure. |
With potassium carbonate; acetone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine at 20℃; | ||
With hydrogenchloride; water; bromine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With sulfuric acid; at 0 - 100℃; | Method B1_1 Synthesis of intermediate: 2-((5-chloro-8-hydroxyquinolin-7- yl)methyl)-1 H-isoindole-1,3(2H)-dione; 2-(Hydroxymethyl)-1 H-isoindole-1 , 3(2H)-dione (14.8g, 83mmol) was added portionwise to a well stirred solution of 5-chloro-8-hydroxyquinoline (15g, 83mmol) in concentrated sulphuric acid (150ml) cooled to O0C. After addition was complete the reaction was heated to 1000C overnight. The mixture was allowed to cool to RT then poured onto crushed ice (1000ml) and the resulting yellow precipitate filtered, washed with water and dried in vacuo overnight. The solid <n="48"/>was triturated with ethanol and hexane to yield an off-white solid (16.7g, 59%). MS 338 (M+); 1H NMR (DMSO-d6), 400 MHz delta: 10.24 (bs, 1 H), 8.95 (d, 1 H), 8.48 (d, 1H), 7.41-7.92 (m, 4H), 7.72 (dd, 1 H), 7.57 (s, 1 H), 4.96 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sulfuric acid; potassium nitrate at 5 - 10℃; for 1h; | |
81% | With sulfuric acid; nitric acid In water at 0℃; for 2h; | 1.a EXAMPLE 1; The preparation of N-(5-chloro-8-hydroxyquinolin-7-yl)-3,3-diphenylpropionamide (“A1”) is carried out analogously to the following scheme a) 10 g of 5-chloroquinolin-8-ol are dissolved in 56 ml of conc. H2SO4, a mixture of 100% of 2.8 ml of HNO3+0.5 ml of H2O is added dropwise with cooling and stirring at max. 0° C., and the mixture is subsequently stirred for a further 2 h without cooling.Work-up: The mixture is stirred into 300 ml of ice/H2O, the resultant precipitate is separated off, washed a number of times with H2O, stirred in a little cold MeOH, filtered off with suction and washed with ether, giving 10.2 g of 5-chloro-7-nitroquinolin-8-ol (81%), m.p. 201-202°; HPLC: RT 5.36 min. |
79% | With sulfuric acid; nitric acid Inert atmosphere; |
76% | With sulfuric acid; nitric acid at 0℃; for 1h; | |
76% | With nitric acid In sulfuric acid | 1.A A. A. 5-Chloro-7-nitro-8-hydroxyquinoline To a solution of 5-chloro-8-hydroxyquinoline (90.0 g, 0.5 mol) in sulfuric acid (500 ml) at 0° C. was added 90% nitric acid (0.6 mol) at such a rate that the temperature did not exceed 2° C. The clear solution was stirred for one hour at 0° C., and then allowed to slowly warm to room temperature. The mixture was poured into ice (2 liter) and stirred overnight. The yellow precipitate was filtered, washed with water and dried. The yellow cake was crystallized from methylethylketone giving 85.0 g (76% yield) of solid. M.P. 192°-194° C. |
76% | With sulfuric acid; nitric acid | 1.A A. A. 5-Chloro-7-nitro-8-hydroxyquinoline To a solution of 5-chloro-8-hydroxyquinoline (90.0 g, 0.5 mol) 9n sulfuric acid (500 ml) at 0° C. was added 90% nitric acid (0.6 mol) at such a rate that the temperature did not exceed 2° C. The clear solution was stirred for one hour at 0° C., and then allowed to slowly warm to room temperature. The mixture was poured into ice (2 liter) and stirred overnight. The yellow precipitate was filtered, washed with water and dried. The yellow cake was crystallized from methylethylketone giving 85.0 g (76% yield) of solid. M.P. 192° C.-194° C. |
73% | With nitric acid at 15℃; for 2h; | |
66% | With sulfuric acid; nitric acid at 0℃; | |
63% | With sulfuric acid; nitric acid for 2h; Cooling with ice; | |
With sulfuric acid; potassium nitrate at 10℃; for 8h; | ||
With sulfuric acid; nitric acid at 0 - 2℃; for 1h; | 17.1 Step 1: Preparation of 5-Chloro-7-nitroquinolin-8-ol (compound of Formula 17-2) After cooling the mixture of 5-chloroquinolin-8-ol (Formula 17-1, 20 g, 111 mmol) in sulfuric acid (100 ml) to 0 ° C.,70% nitric acid (8.53 ml, 134 mmol, 1.2 eq) was slowly added dropwise so that the internal temperature did not exceed 2 ° C.After stirring for 1 hour at the same temperature,Ice water was removed and the temperature was raised to room temperature, followed by further stirring for 4 hours. After completion of the reaction, ice water was added dropwise and stirred for 4 hours.The resulting yellow solid was filtered, washed with water and dried to give the target compound (Formula 17-2). | |
With sulfuric acid; nitric acid at 0 - 20℃; for 5h; | 17.1 Step 1: Preparation of 5-chloro-7-nitroquinoline-8-ol (compound of formula 17-2) After the mixture of 5-chloroquinoline-8-ol (Formula 17-1, 20g, 111mmol) dissolved in sulfuric acid (100 ml) was cooled to 0 ° C, 70% nitric acid (8.53 ml, 134 mmol, 1.2 eq) was added. Slowly added dropwise so that the internal temperature did not exceed 2 ° C. After stirring at the same temperature for 1 hour, the ice water was removed and the temperature was raised to room temperature and stirred for 4 hours. After completion of the reaction, ice water was added dropwise and stirred for 4 hours. The resulting yellow solid was filtered, washed with water, and then dried to obtain the target compound (Formula 17-2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: formaldehyd; 7,13-diaza-4,10,16-trithia-1-oxacyclooctadecane In methanol Stage #2: 5-Chloro-8-hydroxyquinoline In benzene for 24h; Heating; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In acetone Heating / reflux; | 238 Prepared from 5-chloro-8-hydroxyquinoline (278.40 mmol) according to the general procedure described above. Purified by recrystallization from hexanes to give the product as a light beige solid (235.81 mmol, 85%). MS (ESI) m/z 220.1; HRMS: calcd for C12H10C1NO + H+, 220.05237; found (ESI-FTMS, [M+H] l+), 220.05229. |
68% | With sodium hydride In N,N-dimethyl-formamide at 20℃; Inert atmosphere; | |
64% | Stage #1: 5-Chloro-8-hydroxyquinoline With sodium hydroxide In water for 0.5h; Stage #2: allyl bromide In water; benzene at 50℃; for 14h; | 3 Example 3. Synthesis of 8-Allyloxy-5-chloroquinoline (3a):A solution of 5-chloro-8-hydroxyquinoline (1 mmol, 180 mg) in aqueous NaOH (0.25 M, 8 mL; 2 mmol) containing tetrabutylammonium bromide as the phase-transfer catalyst (0.1 mmol, 33 mg) was stirred for 30 min., and allyl bromide (1 mmol, 85 μL) and benzene (8 mL) were added and the reaction mixture was stirred vigorously at 50 0C for 14 h. The reaction mixture was partitioned between water (15 mL) and EtOAc (15 mL) after cooling to room temperature and the extraction was repeated twice. The organic layers were combined and washed with 1 M NaOH solution (15 mL) and concentrated. The crude product was purified by flash-column chromatography over silica gel using 1 :2 hexanes-ether as eluent to afford quinoline 3a as a light-brown solid (170 mg, 64%). Analytical data for 3a:Rf 0.55 (7:3 hexanes-EtOAc) mp 49 0C1H NMR (400 MHz, CDCl3) δ: 9.04 (dd, J=AA, 1.3 Hz, IH, H-2), 8.58 (dd, 7=5.5, 1.3 Hz, IH, H-4), 7.56 (dd, J: 5.5, 4.4 Hz, IH, H-3), 7.54 (d, J: 5.8 Hz, IH, H-7),6.99 (d, J=5.8 Hz, IH, H-6), 6.31-6.18 (m, IH, H-21), 5.48 (dt, J=15.2, 3.4 Hz, IH, H-31) 5.37 (dt, J=9.4, 3.4 Hz, IH, H-3"), 4.88 (m, 2H, H-I1)13C NMR (100 MHz, CDCl3) δ: 149.79, 143.67, 132.92, 132.68, 131.23, 126.27, 125.87, 122.30, 121.98, 118.64, 109.07, 69.94 (C-I1)MS (MALDI-TOF) m/z : 220 |
64% | With tetrabutylammomium bromide; sodium hydroxide In benzene at 50℃; for 14h; | |
With basic alumina In chloroform at 65℃; for 0.133333h; Microwave irradiation; | ||
With potassium carbonate In acetone for 24h; Reflux; | Synthesis of [(2-methyl-)2-propenyloxy]quinolines 5a-n General procedure: General procedure: To a solution of 8-hydroxyquinoline 4 (7 mmol) and (2-methyl)allyl bromide (10.5 mmol, 1.5 equiv) in acetone (30 mL) was added potassium carbonate (21 mmol, 3 equiv). After stirring for 24 h at reflux temperature, the reaction mixture was poured into water (15 mL) and extracted with dichloromethane (3 × 15 mL). The combined organic extracts were dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent in vacuo afforded the crude products 5a-n, which were purified by recrystallization. | |
With potassium carbonate In acetone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: concd. H2SO4 / 25 h / Heating 2: 15.5 g / concd. HCl / 52 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.17 g | In toluene for 18h; Heating / reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In dichloromethane at 1 - 4℃; for 1h; Cooling with ice-water bath; | 7 (Synthesis of 5-chloro-8-trifluoromethanesulfonyloxyquinoline) 4.49 g (25 mmol) of 5-Chloro-8-quinolinol and 25 ml of methylene chloride were added. The internal temperature was cooled to 4°C in an ice-water bath, and then 4.5 ml (32.5 mmol) of triethylamine was added thereto. After the internal temperature descends down to 1°C, 4.63 ml (27.5 mmol) of trifluoromethanesulfonic anhydride was added dropwise thereto. The reaction mixture varied to approximately black was stirred in the ice-water bath for 1 hour. After completion of the reaction, the reaction mixture was poured into water and the mixture was extracted with diethyl ether. The extract was washed with 1 mol/L (liter) of hydrochloric acid and water, and then the solvent was distilled off under reduced pressure by an evaporator to give a brown solid. The solid was dissolved in hot hexane (70°C) and suction filtration was carried out to remove the insolbles. The filtrate was cooled to -78°C to give 7.0 g of the desired compound as a pale orange-color solid (yield: 90%). 1H-NMR (300 MHz, CDCl3) δ: 7.20-7.28 (m, 1H), 7.55-7.63 (m, 2H), 8.47 (dd, 1H), 9.11 (dd, 1H) EI-MS (M/e): 295(M+), CI-MS (M/e): 296(MH+) |
90.2% | With triethylamine In dichloromethane at 20℃; for 12h; | 1.1 Step (1), Preparation of Intermediate A. 179 g (1 mol) of 5-chloro-8-hydroxyquinoline was weighed successively,282 g (1 mol) of trifluoromethanesulfonic anhydride,1500 g of dichloromethane,150 g (1.5 mol) of triethylamine in 2 L three-necked flask,Room temperature stirring 12h,To the reaction system was added 500 g of water,Dispensing,Organic phase with 500g of water, washed three times, spin dry,Using a petroleum ether: ethyl acetate = 4: 1 column to afford 280.6 g of the product A,Yield 90.2%Product purity GC was 99.5%. |
83% | Stage #1: 5-Chloro-8-hydroxyquinoline With triethylamine In dichloromethane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at -78 - 20℃; for 12h; Inert atmosphere; |
Stage #1: trifluoromethylsulfonic anhydride; 5-Chloro-8-hydroxyquinoline With triethylamine In dichloromethane at -15℃; for 0.5h; Stage #2: With sodium hydrogencarbonate In dichloromethane; water | 7 Example 7 Intermediate 7-5-chloro-8-(trifluoromethylsulfonyloxy)-quinoline To a suspension of 5-chloro-8-hydroxy-quinoline (8.95 g) in 100 ml of CH2Cl2, 20 ml of TEA was added. The suspension was dissolved then cooled to -15° C. A solution of 21.1 g of triflic anhydride in 50 ml of CH2Cl2 was added dropwise, with cooling. After complete addition, the reaction was stirred at -15° C. for 30 min. The reaction was diluted with CH2Cl2, washed with a solution of NaHCO3, then with water, dried, and the solvent was removed to yield 15.0 g of 5-chloro-8-(trifluoromethylsulfonyloxy)-quinoline. MP: 80-83° C.; MS (ES) m/z (relative intensity): 312 (M++H, 100). Elemental analysis for C10H5ClF3NO3S; Calculated: C, 38.54; H, 1.62; N, 4.4. Found: C, 38.3; H, 1.73; N, 4.5. | |
With triethylamine In dichloromethane at -15℃; for 1h; | 40.b INTERMEDIATE 40b 5-Cl-8-(trifluoromethylsulfonyloxy)-quinoline To a suspension of 5-Chloro,8-hydroxy-quinoline (8.95g) in 100 mL CH2Cl2, TEA is added (20 mL). The suspension dissolved, then cooled to -15°C. A solution of 21.1g of triflic anhydride in 50 mL of CH2Cl2, is added drop by drop with cooling. After complete addition, the reaction was stirred at -15 °C for 1 hour; The reaction was diluted with CH2Cl2, washed with a solution of NaHCO3, then with water dried and the solvent was removed to give 15.0 gr of product. mp 80-83°C. MS (ES) m/z (relative intensity): 312 (M+H+, 100). Elemental analysis for C10 H5 ClF3 NO3 S | |
With triethylamine In dichloromethane at -15℃; for 0.5h; | 7 To a suspension of 5-chloro-8-hydroxy-quinoline (8.95g) in 100 ml of CH2CL2, 20 ml of TEA was added. The suspension was dissolved then cooled TO-15°C. A solution of 21.1 g of triflic anhydride in 50 ml OF CH2CK was added dropwise, with cooling. After complete addition, the reaction was stirred at-15°C for 30 min. The reaction was diluted with CH2C12, washed with a solution OF NAHC03, then with water, dried, and the solvent was removed to yield 15.0 g of 5-chloro-8- (trifluoromethylsulfonyloxy)-quinoline. MP: 80-83°C ; MS (ES) M/Z (relative intensity): 312 (M++H, 100). Elemental analysis for Clo Hs Cl F3 N Os ; Calculated: C : 38. 54; H: 1.62 ; N: 4.4 ; Found: C: 38. 3; H: 1.73 ; N: 4.5. | |
With triethylamine In dichloromethane at -15℃; for 1h; | R.1 To a suspension of 5-chloro, 8-hydroxy-quinoline (commercially available, 8.95 g) in 100 ml CH2Cl2, TEA is added (20 ml). The mixture becomes homogeneous and is then cooled to -15° C. The suspension dissolved, then cooled to -15° C. A solution of 21.1 g of triflic anhydride in 50 ml of CH2Cl2, is added drop by drop with cooling. After complete addition, the reaction was stirred at -15° C. for hour; The reaction was diluted with CH2Cl2, washed with a solution of NaHCO3, then with water dried and the solvent was removed to give 15.0 g of product. MP: 80-83° C. MS (ES) m/z (relative intensity): 312 (M++-H, 100 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: hexamethylenetetramine; 5-Chloro-8-hydroxyquinoline With trifluoroacetic acid at 70 - 100℃; for 74h; Inert atmosphere; Stage #2: With hydrogenchloride In water at 100℃; for 1h; Inert atmosphere; | 3.8. General Procedures for the Synthesis of Selected Quinolinecarbaldehydes Based on the Duff Protocol General procedure: These were based on a procedure described in the literature [28]. To a solution of 1b, 1d, 1e, 1f,1h or 1j (5.0 mmol) in a minimum amount of TFA (7-8 mL) hexamethylenetetramine (1.4 g, 10.0mmol) was gently added under an argon atmosphere. The solution was stirred at 70 °C for 70 h andthen at 100 °C for another 4 h. Subsequently, the obtained suspension was acidified by an aqueoussolution of hydrochloric acid (10%, ~10 mL) and the reaction mixture was kept at 100 °C for 1 h. Thewhole suspension was cooled down to r.t. Next, the obtained reaction mixture was alkalified byaqueous solution of NaOH (10%), and the resulting precipitate was collected in a Buchner funnel,followed by washing with water (3 × 50 mL) and dried to afford a solid. Next, the crude product waspurified by chromatography to yield 2c precipitates as follows, or the crude product was extractedwith CH2Cl2 at Soxhlet apparatus to yield 2h solid as follows: |
40% | With trifluoroacetic acid for 6h; Inert atmosphere; Reflux; | General procedure for the synthesis of 3a/3b A mixture of 5-chloro-8-hydroxyquinoline (0.015 mol), hexamethylenetetramine (HMTA) (4.2 g,0.030 mol) and trifluoroacetic acid (25 ml) was heated under reflux for 6 hunder an argon atmosphere. After cooling, the reaction mixture was poured onto a solution of concd hydrochloric acid (20 ml) in water (220 ml), stirred for1 h and neutralized with NaOH solution to pH 5. The solution was extracted with chloroform (3Χ50 ml), washed with brine solution. Then it was evaporated under reduced pressure and the crude product was purified by chromatography using silica gel (60-120 mesh) and finally by crystallization from ethanol to produce 7-formyl-5-chloro-8-hydroxy quinoline |
37% | With trifluoroacetic acid at 120 - 130℃; for 5h; |
15% | With trifluoroacetic acid for 6h; Reflux; Inert atmosphere; | |
With trifluoroacetic acid | ||
3.3 g | With trifluoroacetic acid for 8h; Reflux; | Latent catalyst preparation Part A: First, the first ligand was prepared by mixing 5-chloro-8-hydroxyquinoline (9 g), hexamethylenetetramine (14 g), and trifluoroacetic acid (150 mL). The mixture was sparged with nitrogen for 15 minutes, heated under reflux for 8 hours, and then cooled to room temperature. Conc. HCl (60 mL) and water (200 mL) were added, and the mixture was stirred for 16 hours, then neutralized to pH 5 with sodium hydroxide solution. The solution was extracted twice with 200 mL chloroform, dried over sodium sulfate, and then eluted with a 3:2 (v:v) mixture of ethyl acetate and chloroform and purified by column chromatography with silica gel, followed by chloroform and ethyl. Recrystallization from a mixture of acetate gave 3.3 g of a solid product. Mass spectroscopy indicated that the product was consistent with 5-chloro-8-hydroxyquinoline-7-carboxaldehyde. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With triethylamine In ethanol at 20℃; for 48h; | 2 Example 2. General Procedure for the Synthesis of 7-(2-amino-2-arylmethyl)-8- hydroxy-quinolinesTo a solution of 5-chloro-8-hydroxyquinoline (1 mmol, 180 mg) in absolute ethanol (15 mL); triethylamine (1 mmol) and aromatic aldehyde (1 mmol) were added and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was was concentrated and the residue was recrystallized from 1 :1 EtOH-H2O.5-Chloro-7-(l-phenyl-l-(iV-morpholino)-methyl)-8-hydroxy-quinoline (2f) Yield: 315 mg, 89% Analytical data for 2f : Rf 0.35 (7:3 hexanes-EtOAc) mp 89 0CH NMR (400 MHz, acetone-de) δ: 8.91 (pair of dds, J=3.4, 1.2 Hz, IH, H-2), 8.53 (pair of dds, J=6.5, 1.4 Hz, IH, H-4), 7.71 (pair of dds, J=6.5, 4.4 Hz, IH, H-3), 7.61 (pair of ds, J=8.0 Hz, 2H, 2,6-Ph), 7.27 (pair of ts, J=8.0 Hz, 2H, 3,5-Ph), 7.15 (d, IH, 4-Ph), 3.71 (br t, J=4.8 Hz, 2H, 2,6-moφholine), 2,88 (br s, 3H, 2,6-morpholine, OH), 2.85 (br s, IH, -N-CH(Ph)-), 2.47 (br s, 4H, 3,5-morpholine)13 C ΝMR (100 MHz, acetone-d6) δ: 153.35, 150.43, 149.97, 149.87, 142.38, 139.99, 133.73, 133.54 (C-4), 129.56 & 128.97 (3,5-Ph), 128.54 & 128.20 (2,6-Ph), 127.26 (4-Ph), 125.92, 125.42, 124.00 (C-3), 123.69 (C-2), 120.86, 111.28, 69.09 & 67.55 (2,6-morpholine), 53.51 (3,5-mopholine)355 (95) |
89% | With triethylamine In ethanol at 25℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With caesium carbonate In N,N-dimethyl-formamide at 120℃; for 3h; | 3 Synthesis of 8-(2-hydroxyethyl)5-chloroquinoline (3b): A mixture of 5-chloro-8-hydroxyquinoline (1 mmol, 180 mg), ethylene carbonate (2 mmol, 180 mg) and Cs2CO3 (0.6 mmol, 195 mg) in dry DMF (10 mL) was stirred vigorously at 120 °C for 3 h. DMF was evaporated under high-vacuum and the residue was dissolved in water (15 mL), extracted twice with dichloromethane (15 mL), and the residue left after evaporation of dichloromethane was chromatographed over silica gel (eluent: 4:1 hexanes-EtOAc). Abiege colored solid was obtained (174 mg, 78%).Analytical data for 3b: Rf 0.32 (7:3 hexanes-EtOAc) m£ 72 0C1H NMR (400 MHz, acetone-d6) δ: 8.97 (dd, J= 3.4, 1.6 Hz, IH, H-2), 8.58 (dd, J = 8.0, 1.6 Hz, IH, H-4), 7.73 (dd, J= 8.8, 4.4 Hz, IH, H-3), 7.66 (d, J= 8.4 Hz, IH, H-7), 7.26 (d, J= 8.4 Hz, IH, H-6), 4.96 (br. s, exch. IH, OH), 4.28 (t, J= 4.8 Hz, 2H, H-I1), 3.99 (br. s, 2H, H-21)MS (MALDI-TOF) m/z : 224 |
78% | With caesium carbonate In N,N-dimethyl-formamide at 120℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
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In ethanol at 20℃; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
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In ethanol at 20℃; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
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82% | With potassium carbonate In N,N-dimethyl-formamide at 5 - 50℃; | Synthesis and analysis of cloxyquin analogues which were analyzed in detail in this study. General procedure: Cloxyquin (500 mg, 2.784 mmol) was dissolved in N,N-dimethylformamide (10 mL) and to the solution, K2CO3 (1.15 g, 8.352 mmol for A2764; 770 mg, 5.568 mmol for A2793) was added. The reaction mixture was cooled to 5 °C, then the appropriate alkylating reagent (4.176 mmol), N-2-chloroethyl-N,N-diethylamine hydrochloride (for A2764) or ethyl bromoacetate (for A2793), was added. The resulting mixture was strirred at 50 °C overnight (for A2793) or at room temperature for 7 hours (for A2764), while monitoring tlc. Then, the reaction mixture was concentrated under reduced pressure, and to the residue water was added (20 mL). It was extracted with ethyl acetate (3×20 mL). The organic phase was dried over MgSO4 and the solvent was evaporated under reduced pressure. |
Stage #1: 5-Chloro-8-hydroxyquinoline With potassium carbonate In acetone at 20℃; Stage #2: ethyl bromoacetate In acetone Reflux; |
Yield | Reaction Conditions | Operation in experiment |
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68% | Stage #1: 5-Chloro-8-hydroxyquinoline; acetyl chloride With aluminum (III) chloride at 0 - 130℃; for 16h; Stage #2: With hydrogenchloride In water | 47.1 A mixture of 5-chloro-8-quinolinol (6.67 g, 37.1 mmol, from Aldrich), aluminum trichloride (20.00 g, 150.0 mmol), and acetyl chloride (12.1 mL, 170 mmol) was stirred at 0 °C for 4 hours, then heated at 130 °C for 12 hours, cooled, and decomposed with water (39 mL) (caution.) and cone. HC1 (13 mL). The solid product was filtered, and dried under reduced pressure. The solid obtained was then dissolved in 50 mL of water. To the solution was added 100 mL of dichloromethane. The mixture was cooled with an ice bath and its pH was adjusted to 4 with 20% NaOH. The mixture was filtered under reduced pressure. The solid collected was washed with water and air dried to give the desired product (~2 g). The layers of the filtrate were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with water, brine, dried over magnesium sulfate and concentrated to give additional desired product (total 5.6 g, 68%). LCMS calculated for CnH9ClN02 (M+H)+: m/z = 222.0; Found: 222.0. |
68% | With aluminum (III) chloride at 0 - 130℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
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90% | Stage #1: 5-Chloro-8-hydroxyquinoline With potassium carbonate In acetone at 20℃; for 0.5h; Stage #2: methyl iodide at 20℃; | 11.A Step A: Preparation of 5-Chloro-8-methoxyquinoline 5-Chloro-8-hydroxyquinoline (1.8 g, 10 mmol) was dissolved in 200 mL of acetone, triturated and dried anhydrous potassium carbonate (2.7 g, 20 mmol) was added, and the mixture was stirred at room temperature for 30 minutes.Iodomethane (2.8 g, 20 mmol) was slowly added dropwise, stirred at room temperature overnight, and the reaction was monitored by TLC.After the reaction was completed, the solvent was evaporated under reduced pressure, an appropriate amount of water was added, extracted with dichloromethane (150 mL×3), the organic phases were combined, washed once with saturated sodium chloride solution, and dried over anhydrous sodium sulfate overnight.After filtration, the solvent was evaporated under reduced pressure, and it was directly used in the next reaction without purification.Yield 90.0%. |
87% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; | |
84% | With potassium hydroxide In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; |
Stage #1: 5-Chloro-8-hydroxyquinoline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 5h; Inert atmosphere; | ||
Stage #1: 5-Chloro-8-hydroxyquinoline With potassium carbonate In acetone at 20℃; for 0.5h; Stage #2: methyl iodide In acetone at 60℃; for 8h; | 4.1.2. General procedure for the synthesis of compounds 7a-i General procedure: The K2CO3 (2.7 g, 0.02 mol) or KOH (1.6 g, 0.03 mol) was addedto a solution of 5-substituted 8-hydroxy quinoline 4a-c (0.01 mol)in acetone or THF (200 mL) at ambient temperature and the mixturewas stirred for 30 min. Then the methyl iodide (CH3I) (2.8 g,0.02 mol) was added dropwise and stirred overnight. The mixturesolution was concentrated to dryness, added water and extractedwith CH2Cl2 (150 mL 3). Finally, the organic layers were combined,washed with brine, dried with Na2SO4, filtered and evaporated.5a-c were obtained as brown oil, which could be usedwithout further purification. | |
92 % | With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere; | 113 Synthesis of 5-chloro-7-nitroquinoline-2-deuterium-8-ol (113) At 0°C, iodomethane (0.68mL, 10.8mmol) was slowly added dropwise5-Chloro-8-hydroxyquinoline (113a) (1.5g, 8.35mmol) and potassium carbonate(2.3 g, 16.7 mmol) in N,N-dimethylformamide (15.0 mL).The resulting mixture was warmed to room temperature, stirred for 16 hours, diluted with water (50.0 mL),Extract again with dichloromethane (20.0 mL x 2). The organic phases were combined, washed with saturated brine (10.0 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.The resulting residue was purified by silica gel column chromatography (gradient elution, eluent: petroleum ether/ethyl acetate=8/1-2/1) to obtain 5-chloro-8-methoxyquinoline (113b ) (1.48 g, 92% yield). |
Yield | Reaction Conditions | Operation in experiment |
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60% | In ethanol at 80℃; for 18h; | 35 Example 35:3-Amino-l-(3-bromo-4,5-dimethoxy-phenyl)-9-chloro-lH-4-oxa-5-aza-phenanthrene-2- carbonitrile (35)(35) 5-Chloro-8-hydroxyquinoline (790.2 mg, 4.4 mmol), 5-bromo-3,4-dimethoxy-benzaldehyde (1.077 mg, 4.4 mmol) and malononitrile (295 mg, 4.4 mmol) were taken in 40 ml ethanol at room temperature, charged with DABCO (48.4 μ, 1.46 mmol) and then stirred at 80 °C under LC-MS control for 18 h. The reaction mixture was cooled down to room temperature, diluted with water to about 100 ml and the solid were collected by filtration. It was washed with 50% aqueous ethanol. The solids were taken in 15 ml 2-propanol and stirred at 60 °C for 10 minutes, cooled down by dipping the flask in an ice bath, the solids were filtered and dried under vacuum to get the pure title compound (1.25 g, 2.64 mmol, 60 %). |
60% | With 1,4-diaza-bicyclo[2.2.2]octane In ethanol at 20 - 80℃; for 18h; | 35 5-Chloro-8-hydroxyquinoline (790.2 mg, 4.4 mmol), 5-bromo-3,4-dimethoxy-benzaldehyde (1.077 mg, 4.4 mmol) and malononitrile (295 mg, 4.4 mmol) were taken in 40 ml ethanol at room temperature, charged with DABCO (48.4 μ, 1.46 mmol) and then stirred at 80 °C under LC-MS control for 18 h. The reaction mixture was cooled down to room temperature, diluted with water to about 100 ml and the solid were collected by filtration. It was washed with 50% aqueous ethanol. The solids were taken in 15 ml 2-propanol and stirred at 60 °C for 10 minutes, cooled down by dipping the flask in an ice bath, the solids were filtered and dried under vacuum to get the pure title compound (1.25 g, 2.64 mmol, 60 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With hydrogen In water at 20℃; for 0.666667h; | 4 The 100mmol 5-chloro-8-hydroxyquinoline and load 0.6mmol platinum polymer microsphere catalyst Poly (DVB-co-HPMA) Pt and 500 ml of water are added in a reaction kettle, to hydrogen replaces the cauldron five times the air in, and then filled with hydrogen, the reaction at normal temperature and pressure 40 minutes, the aqueous phase is extracted three times with ethyl ether, the merger ether level, ethyl ether evaporate after drying, to obtain 5-chloro-8-hydroxy -1, 2, 3, 4-tetrahydro-quinoline, yield 97%. |
88% | With hydrogen In toluene at 80℃; for 13h; Autoclave; chemoselective reaction; | |
67% | Stage #1: 5-Chloro-8-hydroxyquinoline With H2SiEt2; tris(pentafluorophenyl)borate In chloroform at 85℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether at 20℃; for 1h; | III. Reduction of Substituted Quinolines and Other N-Heteroarenes (Schemes 2-3) General procedure: In a 1.5 mL reaction vial, B(C6F5)3 (0.025 mmol, 5.0 mol %) was dissolved in chloroform (0.60 mL), towhich diethylsilane (1.75 mmol, 3.5 equiv) was added. After shaking briefly, quinolines (1a-p, 0.50 mmol, 1.0equiv) was subsequently added to the above catalyst solution under argon atmosphere. The reaction mixturewas stirred at 25-65 oC for 6-24 h for the reaction of 1a-h, and at 25-100 oC for 2-24 h for the reaction of 1i-p,then allowed to cool down to room temperature and concentrated under reduced pressure to give the crudeproduct. This reaction mixture was then treated with 0.25 N HCl ethereal solution (7 mL) and stirred at roomtemperature for 1 h to give the solid residue, which was subsequently washed with ether. The solid residue wasthen dissolved or suspended in MeOH (1.0 mL) and neutralized with Na2CO3·H2O (0.5 g) at 0 oC. After stirringfor 2 h, MeOH was removed under reduced pressure, and the neutralized reaction residue was dissolved inCH2Cl2 and washed with brine (5 mL) and water (5 mL). The crude product was then obtained from the organicphase of CH2Cl2 solution and finally purified by column chromatography on silica gel to give 2a-h(EtOAc/Hexane = 1/9) and 2i-p (EtOAc/Hexane = 3/7). |
With sodium tetrahydroborate In water; N,N-dimethyl-formamide at 60℃; for 8h; Inert atmosphere; | 2.4. Catalytic reactions Precatalyst (50 mg), NaBH4 (or NaBD4) (3e12 mmol), 1 mmol ofthe N-cyclic substrate and 5 ml deionized and degassed water (orD2O) were placed in a 25 ml three-necked flask equipped with areflux condenser and a pressure release valve to discharge thehydrogen gas self-generated during the reactions. The operationwas carried out under inert atmosphere. The reaction mixture wasvigorously stirred at different temperatures (25e60 C) for the timeselected. The complete conversion of substrate was determined bysubmitting small samples to spot thin layer chromatography (TLC).After completion, the slurry was centrifuged to separate the catalyst.The solid phase obtained was washed with deionized H2O andthen several times with ethyl acetate to remove all organic residue.The filtrate was collected, extracted with ethyl acetate and theextract dried over anhydrous MgSO4. After removal of the solvent invacuo, the corresponding product was obtained. In some cases, asilica-gel column chromatography was used to purify the product(isolated yield). The product analysis and identification was conductedby comparing the NMR spectral data with those of thepublished pure substances (all analyzed by 1H NMR and 13C NMRon Bruker Avance II 400 MHz spectrometer). The reaction selectivitieswere obtained from the NMR spectra by integration ofcharacteristic peaks for the product and reactant. | |
86 % | With ammonia borane In acetonitrile at 80℃; Sealed tube; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
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91% | 500 mL of 4-methyl-2-pentanone was added to the reaction flask, and 5-chloro-8-quinolinol (0.476 mol) and potassium carbonate (0.6 mol) were respectively added under stirring. The mixture was heated to azeotropy under normal pressure for a continuous Boiling dehydration reaction 2h.The obtained organic phase in step (1) was then added dropwise under refluxing conditions, and the azeotropic reaction was continued for 2h.The reaction mixture was then cooled to room temperature, filtered with suction and the filtrate was collected.The filtrate was added 200mL of water, 60 C washed with water, the organic continue to use 10% by weight of acetic acid to adjust the pH to 7.The organic phase was subjected to azeotropic dehydration under atmospheric pressure for 2 hours, then the solvent was collected by distillation under reduced pressure and recycled for the next batch of reactions.After distillation, the reaction flask was allowed to cool to room temperature and 160 g of 4-methyl-dipentanone was added.Heated to 60 C and then slowly cooled to -10 C to precipitate a solid.Filtered by suction, the solid was collected to give 152.8 g of product in a yield of 91.0% and a purity of 99.5%. | |
A solution 53.9 g (0.30 mol) of 5-chloro-2-hydroxyquinoline ("CHQ") in 136 g of NMP (N- methyl pyrolidinone) and 60 g of toluene was stirred at 45C in a 1 L jacketed vessel. A solution of sodium hydroxide (25%) (1 1 .4 g, 0.285 mol) was added over 20 minutes. The temperature was raised to 85C and the water was removed under vacuum by azeotropic distillation. When all the water was removed, a further 35 g of toluene is distilled. K2C03 (4.15 g, 0.03 mol) was added to the reaction mixture, followed by the addition of chloro-acetic acid-1 -methylhexyl ester 59.15g (0.360 mol) over 1 hour. When the addition was complete, the temperature was raised to 95C and the reaction mixture is stirred for a further 3 hours. After control of the reaction completion the solvent was removed under vacuum to obtain the crude cloquintocet-mexyl as a melt. | ||
Example 1 Preparation of (RS)-1-methylhexyl (5-chloroquinolin-8-yloxy)acetate (cloquintocet-mexyl) A solution 53.9 g (0.30 mol) of 5-chloro-2-hydroxyquinoline ("CHQ") in 136 g of NMP (N-methyl pyrolidinone) and 60 g of toluene was stirred at 45 C. in a 1 L jacketed vessel. A solution of sodium hydroxide (25%) (11.4 g, 0.285 mol) was added over 20 minutes. The temperature was raised to 85 C. and the water was removed under vacuum by azeotropic distillation. When all the water was removed, a further 35 g of toluene is distilled. K2CO3 (4.15 g, 0.03 mol) was added to the reaction mixture, followed by the addition of chloro-acetic acid-1-methylhexyl ester 59.15 g (0.360 mol) over 1 hour. When the addition was complete, the temperature was raised to 95 C. and the reaction mixture is stirred for a further 3 hours. After control of the reaction completion the solvent was removed under vacuum to obtain the crude cloquintocet-mexyl as a melt. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.5% | With ammonia; In water; at 60℃; for 2h; | General procedure: Zn(HPB)(Clq) was prepared by adding a solution of zinc sulfate (1mM) in water to a solution of the 5-chloro-8-hydroxyquinoline(1mM) and <strong>[835-64-3]2-(2-hydroxyphenyl)benzoxazole</strong> (1mM) in acetonitrile. The pH was adjusted to neutral by adding ammonia solution. After stirring the mixture for 2h at 60C on a magnetic stirrer, a crude product precipitated from the solution. The cream colored precipitate was washed with deionised water to remove the excess metal ions and then recrystallized with acetonitrile, to give a pure Zn(HPB)(Clq) as shown in Scheme 1. The recrystallized materials were further purified by vacuum sublimation technique. The chelate gave yellow fluorescence under UV light. Zn(HPB)(Cl2q) was prepared as shown in the reaction, following the above-said procedure using 5,7-dichloro-8-hydroxyquinoline instead of 5-chloro-8-hydroxyquinoline. The chelate gave orange-yellow fluorescence under UV light. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium phosphate; TPGS-750-M In water at 45℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
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54% | at 130 - 180℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
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50% | at 130 - 180℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
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66% | at 130 - 180℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
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In tetrahydrofuran; at 20℃;Inert atmosphere; | General procedure: The preparation procedure for two homoleptic 8-quinolinolato iron(III) complexes (Qa3FeIII and Qb3FeIII) could be found in our recent publication [34].The preparation procedure for two heteroleptic Q3FeIII complexes is described as follows: the ligand Qb or Qa (4mmol) was dissolved in 20ml of anhydrous THF to obtain a solution, designated as ?A?, and FeCl2·4H2O (2mmol) was dissolved in 20ml of THF to form the solution ?B?, to which an excess amount of iron powder was added to prevent oxidation of ferrous ions to ferric ions. The solution ?A? was added dropwise to the solution ?B? under N2 and then the reaction mixture was stirred at room temperature until the ligand Qb or Qa was consumed completely. After the iron powder was removed with a magnetic separation method, another lignad Qa or Qb (2mmol) in anhydrous THF (10ml) was added dropwise to the above reaction mixture under air, and then the reaction mixture was stirred at room temperature until the ligand Qa or Qb was consumed completely. Finally, the resulting precipitate was filtrated and washed with ethanol for three times. After air-drying, a black solid (denoted as Qa1Qb2FeIII or Qa2Qb1FeIII) was obtained in 90-95% yield. The Fe contents of four 8-quinoliolato FeIII complexes were determined by conventional EDTA titration and the results are listed in Table 1. Herein, the found values for Qa3FeIII and Qb3FeIII were in good agreement with those calculated from the corresponding formulae of the hexadentate structures. However, the found value for Qa1Qb2FeIII or Qa2Qb1FeIII was obviously higher than it?s calculated one, this is likely because a small amount of iron powder or tetradentate Qa2FeII/Qb2FeII complexes still remains in the heteroleptic Q3FeIII complex with a hexadentate structure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine In dichloromethane at 20℃; for 1.75h; | Compound 11a To a solution of chloropropylsulfonyl chloride (886 mg, 5.00 mmol) and Et3N (710 μL, 5.09 mmol) in CH2Cl2 (20 mL) was added 5-chloroquinolin-8-ol (899 mg, 5.01 mmol). After stirring for 1.5 hr at room temperature, an additional amount of chloropropylsulfonyl chloride (354 mg, 2.00 mmol) and Et3N (307 μL, 2.20 mmol) were added to the reaction mixture, and the resulting mixture was stirred for further 15 min. After work-up, the crude mixture was purified by Isolera One system (hexane/AcOEt) to obtain 11a as a pale yellow solid (1542 mg, 96%). 1H NMR (500 MHz, CDCl3/TMS): δ9.00 (dd, J = 1.7,4.2Hz, 1H), 8.59 (dd, J= 1.7, 8.6 Hz, 1H), 7.65 (d, J = 8.3Hz, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.60 (dd, J = 4.2,8.6 Hz, 1H), 3.81 (t, J = 7.4Hz, 2H), 3.79 (t, J = 6.3 Hz, 2H), 2.65 (tt, J = 6.3, 7.4Hz, 2H); 13C NMR (125 MHz, CDCl3): δ151.5,144.4, 141.8, 133.4, 130.3, 127.5, 126.3, 123.6, 122.9, 49.6, 42.8, 27.0; IR (neat): 2967, 1587, 1565, 1495, 1464, 1368, 1350, 1160, 1145cm-1; HRMS (ESI+) calcd for C12H11Cl2NNaO3S (M+Na) 341.9734: Found 341.9733. |
Yield | Reaction Conditions | Operation in experiment |
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100% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 5h; | Compound 11b To a solution of 5-chloroquinolin-8-ol (1078 mg, 6.00 mmol), Et3N (1000 μL, 7.17 mmol), and DMAP (29 mg) in CH2Cl2 (20 mL) was added 4-chlorobutylsulfonyl chloride (1233 mg, 6.45 mmol) at 0 °C. After stirring for 2.5 hr at room temperature, an additional amount of 4-chlorobutylsulfonyl chloride (623 mg, 3.26 mmol) and Et3N (500 μL,3.59 mmol) were added to the reaction mixture, and the resulting mixture was stirred for further 2.5 hr. After work-up, the crude mixture was purified by Isolera One system (hexane/AcOEt) to obtain 11b as a colorless solid (2248 mg, quant.). 1H NMR (500MHz, CDCl3/TMS): δ 9.01(dd, J = 1.4,4.1Hz, 1H), 8.60 (dd, J = 1.4, 8.5Hz, 1H), 7.66 (d, J = 8.3 Hz,2H), 7.64 (d, J = 8.3 Hz,1H), 7.60 (dd, J = 4.1, 8.5 Hz, 1H), 3.67 (t, J = 7.6 Hz, 2H), 3.62 (t, J=6.3Hz, 2H), 2.32 (tt, J = 7.6, 7.6 Hz, 2H), 2.03 (tt, J = 6.3, 7.6 Hz, 2H); 13CNMR (125 MHz, CDCl3): δ 151.4,144.5, 141.9, 133.4, 130.2, 127.5, 126.3, 123.6, 122.9, 51.3, 44.0, 30.8, 21.3; IR(neat): 2959, 2917, 1590, 1494, 1464, 1353, 1162, 1139 cm-1; HRMS (ESI+) calcd for C13H13Cl2NNaO3S (M+Na) 355.9891: Found 355.9872. |
Yield | Reaction Conditions | Operation in experiment |
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With formic acid; quinindine In acetonitrile at 75℃; for 144h; Inert atmosphere; | 20 Preparation of enantiomerically pure 5-Chloro-7- [ ( ) - [ (4-methylpyrimidin-2-yl) amino][4-( rifluoromethyl)phenyl]methyl] quinolin-8-ol In inert atmosphere 3 ml of acetonitrile , 540 mg (1,67 mmol, 0,5eq) of quinidine, 129 mg (2,8 mmol, 0,84 eq) of formic acid, 364 mg (3,33 mmol, 1,0 eq) of 2-amino-4- methylpirimidine then 580 mg (3,33 mmol, 1,0 eq) of 4- ( trifluoromethyl) benzaldehyde, and finally 716 mg (4 mmol, 1,2 eq) 5-chloro-8-hydroxyquinoline were added into a round bottom flask. The mixture was stirred for 6 days at 75°C temperature. The reaction mixture was processing up as usual to get the pure product. C22H16C I F3 4O ; mass (ESI positive mode): 445 (444+H+). HPLC (Lux4; Hexane: Isopropanol 95:5) Tr = 22,8 minute. 1H NMR (500 MHz, D6MS0) δ 10,43 (wide s, 1H) , 8.95-8.91 (m, 1H), 8.47-8.42 (m, 1H) , 8.20 (d, J = 9.6 Hz, 1H) , 8.15 (d, J = 4.9 Hz, 1H), 7.71-7.66 (m, 1H) , 7.65 (d, J = 8.2 Hz, 2H) , 7.58 (d, J = 8.1 Hz, 2H) , 7,09 (1H, d, J = 9,5 Hz), 6,51 (1H, d, J = 4,95Hz), 2,24 (3H, s) ; 13C-NMR (125MHz, D6MSO) : 25,5, 110,5, 118,8, 123,0, 125,0, 125,3, 125,4, 126,6, 127,8, 132,5, 138,7, 147,5, 149,2, 149,4, 161,5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formic acid; quinine In acetonitrile at 75℃; for 144h; Inert atmosphere; | 21 Preparation of enantiomerically pure 5-Chloro-7- [ (S) - [ (4-methylpyrimidin-2-yl) amino] [4-(trifluoromethyl)phenyl]methyl] quinolin-8-ol In inert atmosphere 3 ml of acetonitrile, 540 mg (1,67 mmol, 0,5eq) of quinine, 129 mg (2,8 mmol, 0,84 eq) of formic acid, 364 mg (3,33 mmol, 1,0 eq) of 2-amino-4-methylpirimidine then 580 mg (3,33 mmol, 1,0 eq) of 4- (trifluoromethyl) benzaldehyde, and finally 716 mg (4 mmol, 1,2 eq) 5-chloro-8-hydroxyquinoline were added into a round P-1418 bottom flask. The mixture was stirred for 6 days at 75 °C temperature. The reaction mixture was processing up as usual to get the pure product . C22H16C I F3IS O ; mass (ESI positive mode) : 445 (444+H+) . HPLC (Lux4; Hexane: Isopropanol 95:5) Tr = 22,8 minute. 1H NMR (500 MHz , D6MSO) δ 10,43 (wide s, 1H) , 8.95-8.91 (m, 1H), 8.47-8.42 (m, 1H) , 8.20 (d, J = 9.6 Hz, 1H) , 8.15 (d, J = 4.9 Hz, 1H), 7.71-7.66 (m, 1H) , 7.65 (d, J = 8.2 Hz, 2H), 7.58 (d, J = 8.1 Hz, 2H), 7,09 (1H, d, J = 9,5 Hz), 6,51 (1H, d, J = 4,95Hz), 2,24 (3H, s) ; 13C-NMR (125MHz, D6MSO) : 25,5, 110,5, 118,8, 123,0, 125,0, 125,3, 125,4, 126,6, 127,8, 132,5, 138,7, 147,5, 149,2, 149,4, 161,5. |
Yield | Reaction Conditions | Operation in experiment |
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In neat (no solvent); for 0.5h; | General procedure: Compounds embodied herein were synthesized as shown in the scheme below using a route that employs a microwave-assisted, 3-component Maimich-type reaction (Gilbert, A. M. et al. N-((8-hydroxy-5-substituted-quinolin-7-yl) (phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors ofADAMTS-5 (Aggrecanase-2). l3ioorg Med Chem Lett 18, 6454-7 (2008)) with an average yield of 60%. Afier work- up, each compound was purified by HPLC to >95% purity (LC/MS); All compounds were prepared according to the above scheme following a similar method. To a microwave vial, 0.5 mmol of hydroxyquinoline, 0.5 mmol aldehyde (where R? corresponds to A in formula (I)) and 0.5 mmol amide (where R2 corresponds to R3 in formula (I)) were added. The vial was then heated to 120 C. for 30 mm. The solids were purified by trituration with 1:1 hexanes:ethyl acetate. Thesuspension was filtered and the solids washed 3 times with 1:1 hexanes: ethyl acetate. The solids were then furtherpurified by preparative HPLC prior to testing.Following the guidance above, the following compounds were prepared Other compounds were obtained from com5 mercial sources. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; potassium carbonate In dimethyl sulfoxide at 20℃; for 1h; | 30 Example 30. 5-Chloroquinolin-8-yl sulfurofluoridate To a 2-dram vial containing 5-chloroquinolin-8-ol (50 mg, 0.28 mmol) and (4-acetamidophenyl)(fluorosulfonyl)sulfamoyl fluoride (105 mg, 0.334 mmol) in dimethyl sulfoxide (4 mL), potassium carbonate (115 mg, 0.835 mmol) was added and the reaction solution was stirred at room temperature for 1 hour. The mixture was diluted with ethyl acetate (2*10 ml) and washed with brine (10 ml). The organic fraction was dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by automated column chromatography (4 g silica, 20% ethyl acetate in petroleum ether) to get product as a white solid (69 mg, 95% yield). 1H NMR: (400 MHz, DMSO) δ 9.19 (dd, J=4.2, 1.3 Hz, 1H), 8.70 (d, J=8.6 Hz, 1H), 8.14 (d, J=8.4 Hz, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.90 (dd, J=8.6, 4.2 Hz, 1H). 13C NMR: (101 MHz, DMSO) δ 153.01 (s, 4H), 144.06 (s, 1H), 139.92 (s, 1H), 133.05 (d, J=6.8 Hz, 4H), 131.13 (s, 1H), 126.99 (s, 1H), 126.55 (s, 4H), 124.37 (s, 4H), 122.29 (s, 4H). 19F NMR: (376 MHz, DMSO) δ 41.98 (s, 83H). |
92% | With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 0.166667h; | |
87% | With potassium fluoride; triethylamine; N,N`-sulfuryldiimidazole; trifluoroacetic acid In dichloromethane at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 2h; Inert atmosphere; | |
90% | With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 2h; Inert atmosphere; | 48 Example 48: 5-Chloroquinolin-8-yl (4-(methylamino)phenyl) sulfate 5-Chloroquinolin-8-yl (4-(methylamino)phenyl) sulfate was prepared according to the following procedure. A two-dram vial containing 5-chloro-8-hydroxy-quinoline (72 mg, 0.40 mmol), 4-(tert-butyldimethylsilyloxy)-N-methylaniline (124 mg, 0.521 mmol), and AISF (151 mg, 0.481 mmol) was purged with nitrogen and then acetonitrile (2 mL, purged with nitrogen for 15 minutes) was added, followed by DBU (134 mg, 132 μL, 0.882 mmol) over a period of 30 seconds. The reaction was stirred at room temperature for 2 hours. The reaction was partitioned between EtOAc and brine. The aqueous layer was extracted with EtOAc (2*) and the organic extracts were combined and dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (EtOAc/heptane) to afford the title compound as a white solid (131 mg, 90% yield). Physical State: white solid. 1H NMR: (400 MHz, CDCl3) δ 9.07 (dd, J=4.2, 1.6 Hz, 1H), 8.57 (dd, J=8.6, 1.6 Hz, 1H), 7.61-7.55 (m, 3H), 7.31 (d, J=9.0 Hz, 2H), 6.57 (d, J=9.0 Hz, 2H), 3.87 (s, 1H), 2.82 (s, 3H). 13C NMR: (101 MHz, CDCl3) δ 151.79, 148.57, 145.52, 141.72, 141.49, 133.00, 130.29, 127.50, 125.85, 122.96, 122.32, 121.00, 112.45, 30.73. MS: (ESI) 365.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.3% | With copper(l) iodide; caesium carbonate In water; acetone at 20℃; for 0.583333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | In ethanol for 8h; Reflux; Inert atmosphere; | General Procedure for the Synthesis of Compounds 4a-m, 5a-d, 6a, and 6b General procedure: To a stirred solution of 5-chloroquinolin-8-ol (2, 360 mg, 2.0 mmol) in dry EtOH (10 mL) was added appropriate amines (2.2 mmol) and paraformaldehyde (240 mg, 8.0 mmol). The reaction mixturewas heated to reflux for 8 h under nitrogen atmosphere. After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and then kept in ice-bath for 3 h. The product was precipitated from the reaction mixture. The desired product was filtered off, washed with cold EtOH (3 mL) and dried under vacuum overnight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With piperidine In ethanol at 140℃; for 0.0333333h; Microwave irradiation; | General procedure for synthesis of 2-amino-4-aryl-4H-pyrano[3,2-h]quinoline-3-carbonitrile derivatives(4a-h, 6a-h, 8a-i) General procedure: A reaction mixture of 8-hydroxyquinoline (1), 8-hydroxy-2-methylquinoline (5) or 5-chloro-8-hydroxyquinoline (7)(0.01 mol), with different aryl or hetaryl aldehydes (2a-h,or 2a-i) (0.01 mol) and malononitrile (3) (0.01 mol) inethanol catalyzed by piperidine under microwave irradiationconditions was heated for 2 min at 140 °C. After completionof the reaction, the reaction mixture was cooled to roomtemperature and the precipitated solid was filtered off,washed with methanol, and was recrystallized from ethanolor ethanol/benzene. The physical and spectral data ofcompounds 4a-h, 6a-h and 8a-i are as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate In acetone at 60℃; | 4.2.1. General procedure for the synthesis of ethyl 2-(phenoxy and heteroyloxy)-acetate (3a-l) General procedure: Compounds ( 3a-l ) were obtained by refluxing a mixture of compounds ( 1a-l, 0.013 mol) and ethyl chloroacetate ( 2, 0.026 mol) in dry acetone (50 mL) and anhydrous potassium carbonate (0.019 mol) for 8-10 h. The reaction mixture was cooled and the solvent was removed by distillation. The residual mass was trit- urated with cold water to remove potassium carbonate, and ex- tracted with ether (3 ×50 mL). The ether layer was given a wash with 10% sodium hydroxide solution (3 ×40 mL) followed by wa- ter (3 ×30 mL), dried over anhydrous sodium sulfate and evapo- rated to dryness to acquire crude solid, which, on recrystallization with ethanol gave desired compounds ( 3a-l ) |
With sodium hydroxide In dimethyl sulfoxide at 80℃; | ||
With potassium carbonate In acetone for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In N,N-dimethyl-formamide at 60 - 82℃; for 1.5h; | 1.1; 1.2; 1.3 Example 3 Put in a 500ml four-neck bottle35.8g5- chloro-8-quinolinol (1eq), 79gDMF, 26g methyl chloroacetate (1.2 eq) was stirred open, heated to 60 , 35.8g of potassium carbonate into a batch temperature was raised to 75 , after half an hour incubation temperature rise Incubate at 80-82°C for 1 hour, and sample HPLC to detect that the quinoline content is less than 0.5% and the reaction is over. Add 1000ml of water into a 2000ml beaker, turn on the stirring, pour the reaction solution while it is hot, stir for half an hour, and filter with suction. The filter cake was put into a 500ml single-neck round-bottomed flask, rotary steamed until no water flowed out, weighed 45.1g, and the yield was 90%. |
With sodium hydroxide In dimethyl sulfoxide at 50 - 60℃; | ||
With potassium percarbonate; potassium hydroxide In methanol; dimethyl sulfoxide at 70℃; for 33h; | 1.1; 2.1; 3.1; 4.1; 5.1 Step 1. Synthesis of intermediate 5-chloro-8-quinolinoxyacetic acid methyl ester: Add the purity of 5-chloro-8-hydroxyquinoline to the chemical reaction kettle, After solvent 1 and catalyst 1, start to stir, the speed of the stirrer is 60 rpm, Stir for 3h, add solvent 2 and catalyst 2, control the temperature to 70, Continue to stir for 4h, then add dropwise methyl chloroacetate, and control the reaction temperature to 70°C. After the dropwise addition of methyl chloroacetate is completed, continue to stir for 2h and stand for 24h for precipitation. Centrifuge for solid-liquid separation, collect solids, The intermediate 5-chloro-8-hydroxyquinolinoxyacetic acid methyl ester. The purity of 5-chloro-8-hydroxyquinoline is 97%; The solvent 1 is dimethyl sulfoxide, and the solvent 2 is methanol; Catalyst 1 is potassium hydroxide, and catalyst 2 is potassium percarbonate; The molar ratio of the added amount of the raw materials is: 5-chloro-8-hydroxyquinoline: Methyl chloroacetate: solvent 1: solvent 2: catalyst 1: Catalyst 2=1:1:3:3:0.2:0.2. |
With potassium percarbonate; potassium hydroxide In methanol; dimethyl sulfoxide at 70℃; for 33h; | 1.1; 2.1; 3.1; 4.1; 5.1 Step 1. Synthesize the intermediate 5-chloro-8-quinolinoxy methyl acetate: add 5-chloro-8-hydroxyquinoline, solvent 1, and catalyst 1 to the chemical reaction kettle, and then start stirring, the speed of the agitator Stir at 60rpm for 3h, add solvent 2 and catalyst 2, control the temperature at 70, continue to stir for 4h, then add dropwise methyl chloroacetate, control the reaction temperature at 70, after the dropwise addition of methyl chloroacetate, continue stirring for 2h, Let stand for 24 hours for precipitation, centrifuge for solid-liquid separation, and collect the solid matter, which is the intermediate 5-chloro-8-quinolinoxyacetic acid methyl ester. The purity of 5-chloro-8-hydroxyquinoline is 97%; the solvent 1 is dimethyl sulfoxide and the solvent 2 is methanol; the catalyst 1 is potassium hydroxide, and the catalyst 2 is potassium percarbonate; the raw material The molar ratio of addition is: 5-chloro-8-hydroxyquinoline: methyl chloroacetate: solvent 1: solvent 2: catalyst 1: catalyst 2=1:1:3:3:0.2:0.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In methanol at 65℃; for 48h; | 2-(4-(((5-chloroquinolin-8-yl)oxy)methyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, 3. 5-Chloro-8-quinolinol (0.046 g, 0.25 mmol) was dissolved in 30 mL methanol and then added dropwise to the methanol solution of 2-(4-(bromomethyl)phenyl)-1H-imidazo[4,5-f][1,10]-phenanthroline (0.1 g, 0.25 mmol) and triethylamine (0.034 mL, 0.25 mmol). The mixture was refluxed for 48 h. The reaction was monitoredby TLC by using methanol/NH3 (4: 1) as the eluent. After the reaction completed, evaporation of the solvents were performed. Light yellow solid residue was washed with water. Then dried under vacuum. (yield %90). M.P. > 300 °C (decomp.). FT-IR υ(cm-1): 3151 (NH), 2921(CH), 1651 (C]N), 1279 (CeOeC), 550 (C-Cl). 1H NMR (DMSO-d6)δ(ppm): 13.66 (b, s, 1H, NH), 9.2-7.3 (m, 15H, aromatic-CH), 4.85 (s, 2H,O-CH2). 13C NMR (DMSO-d6): δ (ppm) = 157, 153, 152, 150, 148, 145,142, 135, 134, 133, 129, 128, 127, 124, 123, 118, 116, 115, 107, 71.Elemental analysis (C29H18ClN5O), Calculated (Found) %: C: 71.38(71.34), H: 3.72 (3.64), N: 14.35 (14.28). HRMS (ESI) (m/z) (M + H)+:488.12. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With ammonia In ethanol at 60℃; for 17h; | 2.4.1 Synthesis of single crystal Zn(L1)2(L2) The synthesis method was the same as that of the compound Zn(L1)2. The material was obtained by the reaction of the two ligands, 5-chloro-8-hydroxyquinoline (L1) and 4-dimethylaminopyridine (L2) with zinc acetate (metal ion) at 1:1:1 M ratio in anhydrous ethanol (Fig. 1b). Frist, 0.1796 g of 5-chloro-8-hydroxyquinoline, 0.1222 g of 4-dimethylaminopyridine and 0.2195 g of zinc acetate were dissolved in absolute ethanol, respectively. Next 15 ml of 4-dimethylaminopyridine ethanol solution and 15 ml of zinc acetate ethanol solution was respectively added to a 100 ml round-bottomed flask, which was added in 15 ml of 5-chloro-8-hydroxyquinoline ethanol solution. Then, the pH of the solution was adjusted to 7-8 with ammonia and stirred at 60 for 17 h. When the mother liquor was cooled to room temperature, it was carefully filtered into a clean glass container, and stood to evaporate the excess ethanol. After 4 d, a large number of lumps Zn(L1)2(L2) yellow single crystals were collected at the bottom of the glass container, carefully manually collected, washed with distilled water, and air-dried at room temperature. Crystals of Zn(L1)2(L2) were collected in 76 % yield. Anal. Calc. for C25H20Cl2N4O2Zn (Mr = 544.74): C, 55.12; H, 3.70; N, 10.29. Found: C, 54.38; H, 3.77; N, 9.77 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With ammonia In ethanol at 60℃; for 17h; | 2.3 Synthesis of the compound Zn(L1)2 The material was produced by the reaction of 5-chloro-8-hydroxyquinoline (L1) and zinc acetate (metal ion) at 1:1 M ratio in anhydrous ethanol (Fig. 1 a). First, 0.1796 g of 5-chloro-8-hydroxyquinoline and 0.2195 g of zinc acetate were dissolved in anhydrous ethanol, respectively. Next 15 ml of zinc acetate ethanol solution was added to a 100 ml round-bottomed flask, which was added in 15 ml of 5-chloro-8-hydroxyquinoline ethanol solution. After adjusting the pH to 7-8 by adding ammonia and stirring the temperature at 60 °C for 17 h, the yellow-green precipitates were collected using water and anhydrous ethanol. Finally, the products were dried at 50 °C for 12 h. The powder of Zn(L1)2 was collected in 83 % yield. Anal. Calc. for C18H10Cl2N2O2Zn (Mr = 422.57): C, 47.90; H, 2.15; N, 6.96 [23,24]. Found: C, 50.64; H, 2.39; N, 6.28 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With 10% Pd/C; hydrogen In tetrahydrofuran; methanol at 20℃; for 24.5h; | 1,2,3,4-Tetrahydro-8-quinolinol (Compound 3) Compound 1a (5-chloro-8-quinolinol: 1.26 g, 7.00 mmol)was dissolved in 14 mL of a mixture containing THF andMeOH (1 : 1), added to 10% Pd/C (744.9 mg, 0.70 mmol), andhydrogenated at 1 atm in H2 gas at room temperature. Afterbeing stirred for 24.5 h, the reaction mixture was filtered,and the filtrate was concentrated under reduced pressure. Thecrude product was purified by recrystallization with CHCl3 toafford compound 3 (724.0 mg, 72%) as a pale orange crystal.Analytical data on compound 3 was as follows: 1H-NMR(CD3OD, 400 MHz) δ: 2.05-2.15 (m, 2H), 2.89 (t, J = 6.1 Hz,2H), 3.41-3.49 (m, 2H), 6.78 (d, J = 7.5 Hz, 1H), 6.82 (d,J = 8.1 Hz, 1H), 7.20 (dd, J = 8.1, 7.5 Hz, 1H); 13C-NMR(CDCl3 + MeOH-d4 5 drop, 100 MHz) δ: 19.5, 24.9, 42.5,113.8, 118.1, 120.5, 129.3, 132.2, 150.7; HR-MS (EI) Calcd forC9H11NO ([M]+): 149.0841. Found: 149.0836. |
Tags: 130-16-5 synthesis path| 130-16-5 SDS| 130-16-5 COA| 130-16-5 purity| 130-16-5 application| 130-16-5 NMR| 130-16-5 COA| 130-16-5 structure
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