Structure of 3528-17-4
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CAS No. : | 3528-17-4 |
Formula : | C9H8OS |
M.W : | 164.22 |
SMILES Code : | O=C1CCSC2=C1C=CC=C2 |
MDL No. : | MFCD00006882 |
InChI Key : | CVQSWZMJOGOPAV-UHFFFAOYSA-N |
Pubchem ID : | 19048 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
Example 31 N- [ (l S, 1 aR, 7bR) or (1R, 1aS. 7bS)-1. 1a. 2, 7b-tetrahvdrocvclopronafc1- [1]benzothiopyran-1-yl]-N'-(5-cyano-2-pyridinyl) urea a) 3, 4-dihydro-2H-1-benzothiopyran-4-ol A solution of thiochroman-4-one (9g) in ether (27 ml) was added slowly to a mixture of lithium aluminium hydride (0.53 g) in ether (54 ml). After the end of the addition, the mixture was refluxed for 2 hours. The reaction mixture was cooled and ice was added, followed by water and by a solution of 20% H2SO4. The water phase was washed twice with ether. The ether phase was washed twice with NaOH 2N, and once with water, dried over MgSO4 and evaporated. The clear oil (8.9 g) crystallised after few hours. Rdt = 97% | ||
To a solution of thiochroman-4-one (9.95 g, 60.6 mmol) in anhydrous ethanol (73 mL) was added sodium borohydride (2.29 g) in small portions. The reaction mixture was stirred at room temperature for 1 h, evaporated to dryness, and treated with ice-water. The aqueous layer was acidified (pH ~2), and extracted into ethyl acetate (3 x 100 mL). The combined organic layers were washed with water (1 x 50 ml) and brine (1 x 50 mL), dried (MgSO4), and concentrated to give 9.32 g of compound aa;1H-NMR (DMSO-d6) δ 7.35 - 6.83 (m, 4H), 5.32 (br s, 1H), 4.59 (m, 1H), 3.32 - 3.13 (m, 1H), 2.95 - 2.89 (m, 1H), 2.12 - 2.05 (m, 1H), 1.99-1.92 (m, 1H). Compound aa was converted to compound cc via compound bb following the same procedure in Example 20. | ||
With sulfuric acid; In water monomer; | a 3,4-dihydro-2H-1-benzothiopyran-4-ol A solution of thiochroman-4-one (9 g) in ether (27 ml) was added slowly to a mixture of lithium aluminium hydride (0.53 g) in ether (54 ml). After the end of the addition, the mixture was refluxed for 2 hours. The reaction mixture was cooled and ice was added, followed by water and by a solution of 20% H2SO4. The water phase was washed twice with ether. The ether phase was washed twice with NaOH 2N, and once with water, dried over MgSO4 and evaporated. The clear oil (8.9 g) crystallized after few hours. Rdt=97% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sulfuric acid; at 110℃; for 4h; | Add 3-phenylthiopropionic acid (13.54g, 74mmol) to 50ml of 80% concentrated sulfuric acid,Stir at 110 C for 4h.After cooling to room temperature, the reaction solution was poured into 100 ml of ice water, and extracted with 100 ml of ethyl acetate three times each time. The organic phases were combined, and the organic layer was washed with 100 ml of saturated NaHCO3 solution and 100 ml of water to neutrality, and the organic layer was anhydrous. Dried over sodium sulfate,The solvent was removed in vacuo to obtain 9.7 g of thiochroman-4-one,Yield was 80%. |
60% | With sulfuric acid; at 0 - 20℃; for 16h; | General procedure: Intermediates 1a-c (65 mmol, 1a: 12 g, 1b: 13 g, 1c: 17 g)were added portion wise to 80 mL con. H2SO4 at 0C. Theblood-red colored solution was stirred overnight at rt. After completion of the reaction, which was monitored by TLC,the reaction mixture was poured on ice. The separated solid was filtered, dried under vacuum and recrystallized fromhexane to give intermediates 2a-c. 3.2.1. Thiochroman-4-one(2a)Off-white solid; mp 28-30C; yield 6.4 g (60%); 13CNMR (100 MHz, DMSOd6): δ 26.54 (C1), 39.45 (C2),124.89 (C3), 126.67 (C4), 129.02 (C5), 130.36 (C6), 133.47(C7), 141.0 (C8), 193.95 (C9); 1H NMR (400MHz, CDCl3):δ 2.96-3.00 (m, 2H, C1H); 3.22-3.26 (m, 2H, C2H); 7.15-7.19 (dt, J = 8.4& 1.2 Hz, 1H, C3H); 7.26-7.28 (dt, J = 8.4 &1.2 Hz, 1H, C4H); 7.35-7.39 (dt, J = 8.4 & 1.6 Hz, 1H,C5H); 8.09-8.12 (dt, J = 8.4 & 1.6 Hz, 1H, C6H); IR (KBr,υmax, cm-1): 3027, 2937, 2850, 1728, 1670, 1520, 1418, 1152,891, 826. Anal.Calcd for C9H8OS: C, 65.82; H, 4.91. Found:C, 65.78; H, 4.93. |
With sulfuric acid; at 0 - 20℃; | General procedure: To a mixture of acrylic acid (700 μL, 720mg, 10mmol) and 4-fluorothiophenol (1985 mg, 15 mmol) was added I2 (20% mol, 760 mg, 3 mmol) and the mixture was stirred at 50 C for 24 h. After completion of reaction (monitored by TLC), a cold saturated sodium thiosulfate solution (30 mL) was added and extracted with dichloromethane (2 x 25 mL); the combined organic layers were mixed with a saturated solution of sodium bicarbonate and extracted to remove the unreacted starting material. The aqueous layerwas acidifiedwith 10%HCl and extractedwith dichloromethane (3 x 50 mL). The combined organic layers were dried over Na2SO4, evaporation of the solvent under reduced pressure afforded 1150 mg (64%) of the desired addition product. The product was cooled down to 0 C in an ice bath and 3 mL of concentrated sulfuric acid was added and the reaction mixture was allowed to warm to room temperature for 2 h with magnetic stirring. The reaction was quenched with ice and the mixture was extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed once with water, followed by saturated NaHCO3 solution. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel using hexane/EtOAc (9:1) as eluent to give 570 mg (90%) of pure 2 as a yellow solid. |
With sulfuric acid; at 0 - 20℃; for 0.12h; | General procedure: 3-(phenylthio)propanoic acids B was added slowly to a 100 mL flask filled with 25 mL conc. H2SO4 at 0 C.Then the resultant mixture was warmed up to room temperature and stirred at room temperature forabout 12 hrs. When the reaction is finished as indicated by TLC monitoring, the reaction mixture waspoured onto ice and extracted with CH2Cl2 (3X 30 mL)upon warming up to room temperature. Theorganic layers were combined and dried over anhydrous Na2SO4. It was then filtered, and concentratedunder vacuum. The crude product was purified by flash column chromatography (EtOAc/hexanes, 10%)to afford thiochroman-4-one C in 60-80% yield. | |
With sulfuric acid; at 0 - 20℃; | Thiochromone were prepared according to previously reported procedures.Thiophenols were purchased and used as received. A250 mL flask was fitted with astirrer bar and charged with 1M NaOH (50 mL) and 1M Na2CO3 (50 mL). A solutionof thiophenols S1 (100mmol) in 60 mL EtOH and 3-chloropropanoic acid (11 g, 102mmol) in 40 mL H2O were added respectively to the above solution. The reactionmixture was stirred at room temperature for 2 h, and then temperature increased toreflux. After the reaction was completed as determined by TLC and cooled down toroom temperature, EtOH was evaporated and then the aqueous phase was acidified topH 1~2 with conc. HCl. The solution was extracted with CH2Cl2 for three times andthe combined organic layers were dried over anhydrous Na2SO4, filtered, andconcentrated. The residue was purified by flash column chromatography(hexane/EtOAc, 20/1 to 5/1) to produce 3-(phenylthio)propanoic acid S2 in 85-95%yield | |
With sulfuric acid; at 2 - 20℃; for 2h; | General procedure: To a mixture of acrylic acid (700 mL, 720 mg, 10 mmol)and thiophenol or phenol (15 mmol), I2 (20% mol, 760 mg,3 mmol) was added, and the mixture was stirred at 50 C for24 h. After the completion of the reaction (monitored byTLC), a cold saturated sodium thiosulfate solution (30 mL)was added and extracted with dichloromethane (2 × 25 mL).The combined organic layers were mixed with a saturatedsolution of sodium bicarbonate and extracted to remove theunreacted starting material layer, which was acidified with10% HCl and extracted with dichloromethane (3 × 50 mL).The combined organic layers were dried over Na2SO4, andthe evaporation of the solvent under reduced pressureafforded 64-66% of the desired additional product. Theproduct was cooled down to 2 C in an ice bath, 3 mL ofconcentrated sulfuric acid was added, and the reactionmixture was allowed to warm to room temperature for 2 h,with magnetic stirring. The reaction was quenched with ice,and the mixture was extracted with dichloromethane (3 ×50 mL). The combined organic layers were washed oncewith water, and then with saturated NaHCO3 solution. Thecombined organic layers were washed with brine, dried overNa2SO4, and concentrated under reduced pressure. Theresidue was purified by column chromatography over silicagel using hexane/EtOAc (9:1), as an eluent, to obtainthiochroman-4-one or 4-chromanone, as a white solid(90-85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With chloro-trimethyl-silane; In ethanol; for 4h;Reflux; | Thiochro-man-4-one (0.700g, 4.26mmol) and phenyl hydrazine (0.461g, 4.26mmol) were diluted with EtOH (7mL) and to the solution was added trimethylsilyl chloride (0.463g, 4.26mmol) in one portion. The reaction mixture was heated at reflux for 4h and cooled to room temperature. The solution was basified with saturated NaHCO3 aqueous solution and diluted with EtOAc (10mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate three times (20mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting solid was dispersed in EtOAc:Et2O=1:8 (v/v) solution, filtered, and dried under reduced pressure to give 9 as an ivory solid (0.961g, 4.08mmol, 96%): mp=162-165C; Rf=0.33 (EtOAc:hexane=1:4); 1H NMR (400MHz, DMSO-d6): δ 11.58 (s, 1H), 7.71 (d, J=7.2Hz, 1H), 7.53 (d, J=8.0Hz, 1H), 7.39 (d, J=8.0Hz, 1H), 7.34 (d, J=7.6Hz, 1H), 7.24 (dd, J=8.0, 7.2Hz, 1H), 7.13-7.17 (m, 2H), 7.04 (dd, J=7.2, 7.0Hz, 1H), 4.28 (s, 2H); 13C NMR (100MHz, DMSO-d6): δ 136.7, 132.4, 131.8, 127.5, 127.4, 127.2, 125.84, 125.78, 122.9, 122.4, 119.4, 118.5, 111.4, 105.9, 22.7; IR (ZnSe-ATR) 3336 (w), 1957 (w), 1915 (w), 1871 (w), 1785 (w), 1453 (w), 1440 (w), 1416 (w), 1312 (w), 1276 (w), 1177 (w), 1006 (w), 1036 (w), 918 (w), 864 (w), 761 (m), 733 (vs), 670 (w) cm-1; Anal. Calcd for C15H11NS: C, 75.92; H, 4.67; N, 5.90; S, 13.51. Found: C, 75.92; H, 4.62; N, 5.91; S, 13.63. |
72% | With chloro-trimethyl-silane; In ethanol; for 4h;Reflux; | <strong>[3528-17-4]Thiochroman-4-one</strong> (11.4 g, 69.2 mmol) and phenylhydrazine7.49 g, 6.82 mL, 69.2 mmol) was dissolved in ethanol (100 mL), trimethylsilyl chloride (7.52 g, 8.79 mL, 69.2 mmol) was quickly added thereto and the stopper was closed.The reaction mixture was heated under reflux for 4 hours and then cooled.A saturated aqueous solution of sodium hydrogencarbonate was added until the solution became sufficiently basic,And diluted with ethyl acetate (150 mL).The organic layer was separated and the remaining water layer was extracted three times with ethyl acetate (250 mL x 3). The combined organic layers were washed with saturated aqueous sodium chloride solution,Anhydrous sodium sulfate was added and the mixture was filtered under reduced pressure.The filtrate was removed under reduced pressure, and the remaining solid was dispersed in diethyl ether: ethyl acetate = 8: 1 (v / v) and filtered to give compound 4 as a yellow liquid. (11.8 g, 49.7 mmol, 72%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; at 0 - 20℃;Schlenk technique; | General procedure: To a solution of 5-methoxy-1-tetralone (3.52 g, 20.0 mmol) in anhydrous THF (20 mL)in a Schlenk flask, was added CH2=CHMgBr in THF (1 mol·L-1, 50.0 mL, 50.0 mmol) at 0C. The mixture was stirred for 3-4 h at rt. Saturated solution of NH4Cl (32 mL) was added dropwise at 0C.The aqueous phase extracted with AcOEt, dried under anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (hexanes/AcOEt, 4:1), giving 2d (2.97 g, 14.6 mmol, 73%), as colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; In chloroform; for 5h;Reflux; | General procedure: Tetrahydrothiopyran-4-one or thiochroman-4-one (1 mol) was dissolved in chloroform(20 mL), then the aromatic aldehyde (1mol) and piperidine (0.5 mL) were added, and the reaction mixture stirred and refluxed for 5 h. After completion of the reaction, the solvent was evaporated and the crude product was washed with water two times and finally crystallized in ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; In chloroform; for 5h;Reflux; | General procedure: Tetrahydrothiopyran-4-one or thiochroman-4-one (1 mol) was dissolved in chloroform(20 mL), then the aromatic aldehyde (1mol) and piperidine (0.5 mL) were added, and the reaction mixture stirred and refluxed for 5 h. After completion of the reaction, the solvent was evaporated and the crude product was washed with water two times and finally crystallized in ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 1-butyl-3-methylimidazolium hydrogen sulfate; at 70℃; for 1h;Green chemistry; | General procedure: General procedure for the synthesis of thiochromeno[3,4-d]pyrimidine (4): A dry 50 mL flask was charged with thiochroman-4-one 1 (1 mmol), aromatic aldehyde 2 a-n (1 mmol), thiourea 3 and [Bmim]HSO4 ionic liquid (2 mL). The reaction mixture was stirred at 70 C for 1 h. The progress of the reaction was monitored by TLC (eluent = n-hexane/ethyl acetate: 8/2, v/v). After completion of the reaction, the reaction mixture was cooled to RT and poured into ice cold water, the solid separated was filtered, washed with water, dried and purified by column chromatography using silica gel (ethyl acetate/n-hexane: 2/8, v/v) to afford title compounds 4a-n in good yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; In chloroform; for 5h;Reflux; | General procedure: Tetrahydrothiopyran-4-one or thiochroman-4-one (1 mol) was dissolved in chloroform(20 mL), then the aromatic aldehyde (1mol) and piperidine (0.5 mL) were added, and the reaction mixture stirred and refluxed for 5 h. After completion of the reaction, the solvent was evaporated and the crude product was washed with water two times and finally crystallized in ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; In chloroform; for 5h;Reflux; | General procedure: Tetrahydrothiopyran-4-one or thiochroman-4-one (1 mol) was dissolved in chloroform(20 mL), then the aromatic aldehyde (1mol) and piperidine (0.5 mL) were added, and the reaction mixture stirred and refluxed for 5 h. After completion of the reaction, the solvent was evaporated and the crude product was washed with water two times and finally crystallized in ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; In ethanol; water; at 0℃; | The title compound (I) was synthesized by aClaisen-Schmidt condensation from commercially availablethiochroman-4-one (332 mg, 2 mmol) (Sigma-Aldrich)and 4-dimethylaminobenzaldehyde (355 mg, 2.4 mmol)(Riedel-de Han) were dissolved in abs. ethanol (6 mL),and 40% aqueous KOH solution (4 mL) was slowly addedat 0 C [13]. The reaction mixture was stirred overnight; thecourse of the reaction was followed by TLC. After reactioncompletion, the mixture was poured into iced water and theorange precipitate formed, was filtered and dried (yield,70%). Crystals of (I) suitable for X-ray diffraction analysiswere grown by slow evaporation of a saturated chloroformsolution of (Z)-3-(4-(Dimethylamino)benzylidene)thiochroman-4-one at room temperature (mp: 431-432 K). 1H NMR(δ ppm, CDCl3,400 MHz): 8.16 (d, 1H, Ar, J = 8.1 Hz),7.76 (s,1H, H-C=), 7.37 (d, 2H, Ar, J = 8.8 Hz), 7.21-7.30(m, 3H, Ar), 6.73 (d, 2H, Ar, J = 7.3 Hz), 4.22 (s, 2H, CH2),3.08 (s, 6H, CH3).13C NMR (δ ppm, CDCl3,125 MHz):185.79 (C8), 151 (C14), 140.63 (C2), 138.81 (C10), 132.88(C4), 132.51 (C7), 131.8 (C9), 130.25 (C12 and C16),128.38 (C6), 127.73 (C3), 125.64 (C5 and C11), 112.01(C13 and C15), 40.29 (C17 and C18), 29.59 (C1). GC-MS[EI 70 eV, m/z (abundance %)]: 295 (100), 278 (15), 158(62), 147 (25), 134 (79), 115 (15). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73%Spectr. | With diphenyl diselenide; urea hydrogen peroxide adduct; In dichloromethane; at 20℃; for 24h; | General procedure: UHP (2 mmol) was dissolved in CH2Cl2 (2 mL), and the solutionwas stirred at r.t. A solution of Ph2Se2 (1 mol%) and sulfide (2mmol) in CH2Cl2 (2 mL) was added to the UHP solution. Themixture was stirred at r.t. for 24 h or until complete conversionto sulfoxide was observed by TLC. Extraction was carried outwith CH2Cl2 (3 × 5 mL), after the addition of H2O (5 mL), and thecombined organic solutions were washed with brine (50 mL),dried (MgSO4), filtered, and the solvents removed underreduced pressure. Sulfoxide products were purified where necessaryby column chromatography. Yellow oil; νmax (cm-1) 1694, 1585, 1325, 1282, 1237, 1182, 1120, 1080, 1039, 854; 1H NMR (400MHz, CDCl3): δH 2.86-2.97 (1 H, m), 3.43-3.56 (3 H, m), 7.65-7.68 (1 H, m), 7.75-7.79 (1 H, m),7.87 (1 H, dd, J 8.1, 7.6 Hz), 8.14 (1 H, dd, J 8.0, 7.6 Hz) ppm; 13C NMR (100 MHz, CDCl3): δC30.3, 46.6, 128.5, 128.9, 132.1, 134.6, 145.5, 192.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-chloro-succinimide; In dichloromethane; at 20℃; for 12h;Cooling with ice; | General procedure: To a cool solution (ice bath) of C (10 mmol) in CH2Cl2 (30 ml) was added N-chlorosuccinimide (NCS) (10.5mmol, 1.05 equivalent) in one portion. The resultant mixture was then warmed up to room temperatureand stirred overnight for about 12 hours. It was quenched with water (30 ml) and the organic layer wasseparated. The aqueous layer was extracted with DCM (2 X 30 mL). The organic layers were combinedand dried (Na2SO4). It was then filtered, concentrated under vacuum to give crude product. The crudeproduct was then purified by flash column chromatography (EtOAc/hexanes, 5-10%) to givethiochromone D in 50-70% yield. | |
With N-chloro-succinimide; In dichloromethane; at 0 - 20℃; | General procedure: To a solution of S3 (30.5 mmol) in CH2Cl2 (100 ml) was added N-chlorosuccinimide(NCS) (30.5 mmol, 1.0 equive) in one portion. This was stirred for 20 min at 0 oC,and then allowed to warm to room temprature overnight. Water (50 ml) was addedand the organic layer was separated and dried (Na2SO4), and the product purified bycolumn chromatography (hexane/ acetone, 5/1) to give thiochromone S4 in 40-80%yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; sodium formate; In water; at 30℃; for 24h;Inert atmosphere; Schlenk technique; | General procedure: In a schlenk tube, the chiral ligand (0.05 mmol) and the metallicprecursor (0.025 mmol) are dissolved in the water (4 mL). After 1 hof stirring at 30 C, the sodium formate (10 mmol) and the ketone (1 mmol) were added to the aqueous solution. The biphasic solution was stirred at 30 for the indicated time and follow by TLC untilthe total reduction of ketone. The formed alcohol was separated from the catalyst by simple extraction with pentane (2 8 mL) and the organic layer was dried over MgSO4 and concentrated in vacuo.The crude residue was distilled in order to purify the alcohol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With C17H38BFeNOP2; hydrogen; In ethanol; at 30℃; under 22502.3 Torr; for 3h;Autoclave; | General procedure: General procedure:All catalytic hydrogenation experiments using molecular hydrogen were carried out in a Parr Instruments autoclave (300 mL) advanced with an internal alloy plate include up to 8 uniform reaction vials (4 mL) equipped with a cap and needle penetrating the septum.Representative experiment:Under an argon atmosphere, a vial was charged with Iron Complex of example 2.2 whichdissolved in 2 mL of dried solvent. The resulting yellow solution was stuffed briefly beforeketone or ketoester (0,5 or 1 mmol). The vial was placed in the alloy plate which was theninto the autoclave. Once sealed, the autoclave was purged 5 times with hydrogen, then pressurized to 30 bar and heated to desired temperature. Afterwards, the autoclave was cooledRT, depressurized, and the reaction mixture was analyzed by GC-FID or HPLC as well asProduct isolation was performed via column chromatography using silica gel as stationary phase and n-pentane / ethylacetate or n-pentane / acetone mixture as eluent.Individual reaction conditions:[a] 1 mol% cat., 0.5 mmol substrate, 30 bar, 3h, 30 C, CH2C1 (1,5 mL)[b] 3 mol% cat., 0.5 mmol substrate, 30 bar, 3h, 70 C, iPrOH (1,5 mL)[c] 2 mol% cat., 0.5 mmol substrate, 30 bar, 2h, 50 C, EtOH (1,5 mL)[dl 1 mol% cat., 0.5 mmol substrate, 30 bar, 3h, 70 C, iPrOH (1,5 mL)[f] lmol% cat., 1 mmol substrate, 30 bar, 22h, 40C, n-heptane (1,5 mL)[g] 1 mol% cat., 1 mmol substrate, 30 bar, 3h, 30 C, EtOH (2 mL)[h] 1 mol% cat., 1 mmol substrate, 30 bar, 6h, 30 C, EtOH (2 mL)[i] 1 mol% cat., 1 mmol substrate, 30 bar, 6h, 60 C, EtOH (2 mL)U] 1 mol% cat., 1 mmol substrate, 30 bar, 6h, 30C, EtOH (2 mL) [k] 3 mol% cat., 1 mmol substrate, 30 bar, 3h, 70C, THF (2 mL)SP = side product (Hydrogenation of double bond) | |
With C32H39BrMnN2O2P; potassium tert-butylate; hydrogen; In methanol; at 20℃; under 22502.3 Torr; for 16h;Glovebox; Autoclave; | General procedure: In a glove box, add manganese complex (R, R)-Io (3.3mg, 0.005mmol), potassium tert-butoxide (1.12mg, 0.01mmol), solvent, ketone substrate (0.5 mmol). After sealing the autoclave, take it out of the glove box and fill it with 30 bar hydrogen. The reaction kettle was stirred at room temperature for 16 hours. Slowly release excess hydrogen. The reaction solution was separated by column chromatography to obtain the separation yield. The ee value was determined by HPLC. The reaction results are listed in Table 4. Among them, the absolute configuration of the product is confirmed by the optical comparison with the standard product, where m alcohol is the mass (g) of the product separated by column chromatography, and n ketone is the molar amount of the ketone substrate ( mol), M alcohol is the molecular weight of the product (g/mol). |
Yield | Reaction Conditions | Operation in experiment |
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80% | With sodium hydrogen sulphite; sodium carbonate; 3-chloro-benzenecarboperoxoic acid; In dichloromethane; | Example 1 Synthesis of 3,4-dihydro-2H-1-benzothiopyran-4-one 1,1-dioxide (Compound 1) 12.94 g (60 mmol) of 80% m-chloroperbenzoic acid was added in portions to a solution of 3.28 g (20 mmol) of thiochroman-4-one in methylene chloride (250 ml) while stirring under cooling with ice. The mixture was stirred at 0 C. for one hour and then at room temperature for 43 hours. The reaction mixture was filtered, and the filtrate was washed with a 10% aqueous solution of sodium carbonate, 20% aqueous solution of sodium hydrogen sulfite (twice), 10% aqueous solution of sodium carbonate (twice), and saturated brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The resultant crude product was recrystallized from ethanol to obtain 3.14 g (yield: 80%) of the title compound. |
70% | With dihydrogen peroxide; acetic acid; In water; at 100℃; for 1h; | 1,1-Dioxo-1-thiochroman-4-one. Into a round bottom flask containing thiochroman-4-one (0.804 g, 4.75 mmol), 6 mL of glacial HOAc and, 2.3 mL of a 35% w/w solution of H2O2 (0.914 g, 26.9 mmol) were added and, the solution was heated at 100 C. for 1 h. After the reaction mixture was cooled at room temperature, 10 mL of H2O were added and the product was extracted twice with CH2Cl2 from the aqueous layer. The resultant organic phase was washed once with brine and dried under Na2SO4. After the solvent was removed, a solid was formed which was purified by recrystallization with EtOH. After drying the solid under reduced pressure, 0.649 g (3.31 mmol) of the product was obtained in a 70% yield. 1H NMR (300 MHz, acetone-d6, δ): 8.07 (ddd, J=7.7, 1.3, 0.6, Ar, 1H), 7.99 (ddd, J=7.8, 2.2, 0.7, Ar, 1H), 7.95 (td, J=7.8, 1.5, Ar, 1H), 7.86 (ddd, J=7.7, 6.7, 2.1, Ar, 1H), 3.94 (t, J=6.3, C2, 2H), 3.37 (t, J=6.3, C2, 2H). 13C NMR (75 MHz, acetone-d6): δ 191.3, 142.9, 135.6, 134.1, 131.6, 129.1, 124.0, 49.6, 37.5. Dept 45 NMR (75 MHz, acetone-d6): δ 134.8 (H), 133.2 (H), 128.2 (H), 123.1 (H), 48.8 (H2), 36.7 (H2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; zinc diiodide; trichlorophosphate; In dichloromethane; benzene; | (a) 4-Cyano-2H-1-benzothiopyrane 80 mg of zinc iodide are added to 1.7 g 1-thiochroman-4-one in benzene followed by, dropwise, with stirring at room temperature, 2.4 g of trimethylsilylcyanide. After 8 hours reaction 2.8 ml of POCl3 and 16 ml of pyridine are added and the mixture refluxed for 8 hours. After cooling the mixture is poured onto ice/conc. HCl and, after addition of dichloromethane, separated. The organic phase is dried over MgSO4, concentrated by evaporation and purified by chromatography on kieselgel (eluant hexane/ethyl acetate; 4/1). H-NMR(CDCl3): δ=6.9-7.6 (m, 4H); 6.64 (t, J=5.5 Hz, 1H); 3.45 (d, J=5.5 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
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65% | at 110℃; for 3h; | General procedure: Intermediates 2a-c (36 mmol, 2a: 6.0 g, 2b: 6.56 g, 2c:8.75 g) were dissolved in 35 mL N,N DimethylformamideDimethylacetal (DMFDMA) at rt. The reaction mixture wasstirred at 110C for 3h. After completion of the reactionwhich was monitored by TLC, the reaction mxture was poured on ice. The separated solid was filtered and driedunder vacuum to give intermediates 3a-c. 3.3.1. 3-((Dimethylamino)methylene)thiochroman-4-one(3a)Pale yellow solid; mp 100-104C; yield 5.5 g (65%); 13CNMR (100 MHz, DMSOd6): δ 34.87 (C1), 44.54 (C2),111.65 (C3), 125.62 (C4), 127.34 (C5), 128.97 (C6), 132.25(C7), 134.59 (C8), 142.12 (C9), 149.03 (C10), 182.91 (C11);1H NMR (400MHz, DMSOd6): δ 3.15 (s, 6H, C1H); 4.05 (s,2H, C2H); 7.18-7.22 (m, 1H, C3H); 7.21-7.26 (m, 1H, C4H);7.29-7.34 (m, 1H, C5H), 7.52-7.58 (m, 1H, C6H), 7.55-7.60(m, 1H, C7H); IR (KBr, υmax, cm-1): 3033, 2942, 2856, 1710,1627, 1560, 1437, 1112, 1096, 855, 836. Anal. Calcd forC12H13NOS: C, 65.72; H, 5.97; N, 6.39. Found: C, 65.70; H,5.99; N, 6.35. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium acetate; acetic acid; In toluene;Dean-Stark; Reflux; | General procedure: In a 100 mL round-bottomflask wasplaced with 40 mL toluene containing ammonium acetate (1000 mg) and glacialacetic acid (3 mL). Then malononitrile (30 mmol) and the ketone (33 mmol) wereadded and the reaction was refluxed and stirred vigorously, the water formed inthe reaction was removed by a Dean and Stark trap placed under the refluxcondenser. After the completion of the reaction, the mixture was cooled toambient temperature and diluted with EtOAc, then washed with brine. The organicphase was dried over Na2SO4 and the solvent wasevaporated under reduced pressure. The residue was recrystallized from ethanolcrystallization or chromatography to give pure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With acetic acid; In methanol; for 12h;Reflux; | General procedure: <strong>[3528-17-4]Thiochroman-4-one</strong>s (0.5 mmol) were dissolved in anhydrous methanol (25 mL). The mixture was heated at reflux and then hydrazide (1.0 mmol, 2 equiv.) and glacial acetic acid 60 μL were added. After 12 h at reflux, the resulting precipitate was collected through filtration and washed with methanol. After drying under vacuum, the residue was passed through a small pad of silica gel with ethyl acetate, after evaporation of the solvent acyl hydrazones were obtained as white solids. |
Yield | Reaction Conditions | Operation in experiment |
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20%; 13% | 6-Bromothiochroman-4-one and 6,8-Dibromothiochroman-4-one. Into a round bottom flask kept at room temperature, AlCl3 (1.81 g, 13.5 mmol) and, 1 mL of CH2Cl2 were added. The reaction system was put under nitrogen and stirred for about 7 minutes before adding 1 mL of a CH2Cl2 solution of thiochroman-4-one (1.11 g, 6.77 mmol). After the reaction mixture was stirred for almost 10 minutes, 2 mL of a CH2Cl2 solution of Br2 (1.19 g, 7.44 mmol) were added and, the reaction mixture was stirred at room temperature for 16 h. At the end of this period of time, the reaction mixture was poured into 50 mL of ice-water and, the product was extracted 3 times from the aqueous phase with EtOAc. The resultant organic phase was washed once with brine and dried under Na2SO4. After the crude reaction mixture was purified by flash chromatography (15% EtOAc/85% hex), 0.648 g of a mixture of 6-monobromide (34% pure, 13% yield) and 6,8-dibromo (66% pure, 20% yield) was obtained. 6,8-Dibromo-thiocroman-4-one: 1H NMR (300 MHz, CDCl3, δ): 8.18 (dd, J=2.2, 0.7, Ar, 1H), 7.77 (dd, J=2.2, 0.7, Ar, 1H), 3.22 (m, C2, 2H), 2.94 (m, C2, 2H). 13C NMR (75 MHz, CDCl3): δ 192.0, 142.5, 139.1, 136.0, 131.0, 122.2, 118.2, 37.8, 26.0. |
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