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CAS No. : | 6639-57-2 | MDL No. : | MFCD00526215 |
Formula : | C8H5NOS | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | RHKPJTFLRQNNGJ-UHFFFAOYSA-N |
M.W : | 163.20 | Pubchem ID : | 241608 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 9 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 45.01 |
TPSA : | 58.2 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) : | -6.07 cm/s |
Log Po/w (iLOGP) : | 1.4 |
Log Po/w (XLOGP3) : | 1.73 |
Log Po/w (WLOGP) : | 2.11 |
Log Po/w (MLOGP) : | 0.83 |
Log Po/w (SILICOS-IT) : | 3.29 |
Consensus Log Po/w : | 1.87 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.48 |
Solubility : | 0.539 mg/ml ; 0.0033 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.57 |
Solubility : | 0.441 mg/ml ; 0.0027 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.91 |
Solubility : | 0.202 mg/ml ; 0.00124 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.91 |
Signal Word: | Danger | Class: | N/A |
Precautionary Statements: | P261-P264-P270-P280-P285-P301+P312+P330-P304+P341-P305+P351+P338-P337+P313-P342+P311-P501 | UN#: | N/A |
Hazard Statements: | H302-H319-H334 | 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 |
---|---|---|
83% | With iodine; toluene-4-sulfonic acid In dimethyl sulfoxide at 130℃; for 16h; Schlenk technique; | |
81% | With iodine; oxygen; trifluoroacetic acid In ethyl acetate at 70℃; for 20h; Irradiation; | |
80% | With iodine; oxygen In dimethyl sulfoxide at 160℃; for 0.75h; Microwave irradiation; | 4. Experimental section General procedure: A 2-5 mL microwave compatible, disposable vial was charged with the requisite methyl heteroarene (0.308 mmol, 1.00 equiv) in reagent grade dimethylsulfoxide (2.0 mL, 0.15 M) at ambient temperature. Subsequently, I2 (82.0 mg,0.32 mmol, 1.05 equiv) was charged in one portion followed by purging of the vial head space with O2. The resulting dark-brown solution was capped with an appropriately sized microwave vialcap and placed in a microwave reactor (high power level) for 0.75 hat 160 °C. The resulting dark brown mixture was cooled to ambient temperature, diluted with minimal ethyl acetate, and transferred toa separatory funnel. The combined organics were treated with a 3 mL of a saturated, aqueous solution of sodium thiosulfate and then separated. The aqueous layer was back-extracted with ethyl acetate (3 10 mL). The combined organics were washed with water (10 mL) to remove residual dimethylsulfoxide and then a saturated aqueous sodium chloride solution (10 mL). The mixture was dried over anhydrous sodium sulfate, filtered through a cotton plug, and subsequently evaporated under reduced pressure at ambient temperature to afford the crude material which was purified using automated flash column chromatography as described below. |
71% | With C15H11ClN4SZn; p-benzoquinone In <i>tert</i>-butyl alcohol for 8h; | 2.5. Photo-oxidation of methyl arenes 25 mg of photo-catalyst was placed in 10 mmol of methyl arene in a10 mL cylindrical quartz glass reactor. Then 25 mg of superoxide orhydroxyl radical scavengers(benzoquinone (BQ) / t-butyl alcohol (TB))was added [22]. The photo-oxidation experiments were carried outunder visible light (300 Watts Tungsten lamp) for 8 h [13]. The reactionmixture was monitored with TLC. After completion of reaction, thephoto-catalyst was filtered and washed with distilled water andextracted by using ethyl acetate. The crude products were purified bysimple filter column to yield pure aldehydes (Scheme 2) with 70 to 85%yields. |
70% | With selenium(IV) dioxide In 1,4-dioxane; lithium hydroxide monohydrate for 12h; Reflux; | |
56% | With copper(II) dichloride dihydrate; oxygen In N,N-dimethyl-formamide at 130℃; for 36h; Sealed tube; | |
41% | With selenium(IV) oxide | 32 Example 32; 1, 3-BENZOTHIAZOLE-2-CARBALDEHYDE (7h) The title compound was prepared from 2-methyl-1, 3-benzothiazole (6h) and selenium dioxide using methods as described in the literature for similar compounds (Conte et AL., 1967) IN 41% YIELD. |
32% | With manganese(IV) oxide In propan-2-one for 24h; Heating; | |
With perchloric acid; CAN In lithium hydroxide monohydrate; glacial acetic acid at 35 - 50℃; study of the kinetics of the oxidation reaction of the methyl group of various bicyclic derivatives by Ce(IV); activation parameters and ΔS(excit.) are given; | ||
With selenium(IV) oxide | ||
Multi-step reaction with 2 steps 1: 77 percent / dimethylformamide / 24 h / 140 °C 2: 77 percent / NaIO4 / tetrahydrofuran; H2O / 0.5 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: 64 percent / iodine 2: 20 percent / pyridona / various solvent(s) / 5 h / 145 °C | ||
Multi-step reaction with 3 steps 1: pyridine; iodine / Behandeln des Jodids mit NaClO4 in H2O 2: aqueous NaOH; pyridine 3: aqueous HCl | ||
With selenium(IV) dioxide In 1,4-dioxane at 110℃; for 12h; | 6.1. Benzo[d]thiazole-2-carbaldehyde (14a) 2-methylbenzo[d]thiazole (13a, 745mg, 5mmol) was refluxed with selenium dioxide (2775mg, 25mmol) in dioxane for 12h. After completion of the reaction the black solid of Selenium was filtered off on celite and the dioxane was removed under reduced pressure. Water was added to the reaction mixture and the compound was extracted using ethyl acetate. The compound was further purified using column chromatography on silica gel 60-120 mesh to afford the pure solid in moderate yield (52%). 1H NMR (300 MHz, CDCl3): 10.18 (s, 1H), 8.26 (dd, J=5.3, 1.5 Hz, 1H), 8.03 (dd, J=4.5, 1.5 Hz, 1H), 7.62 (dt, J=5.3, 2.3 Hz, 2H); ESI-MS: 164 [M+H]+. | |
With iodine; dimethyl sulfoxide at 110℃; for 1h; | General Procedure General procedure: In a 25 mL round bottom flask equipped with a magnetic stir bar, The 2-methylquinoline (80 mg, 0.56 mmol) was dissolved in DMSO (4 mL) and molecular iodine (20 mol%)) was added and heated at 110 °C for 1 h. Next, o-phenylenediamine (0.56 mmol) was added and the resulting solution stirred continuous for 7 h. After this time, the reaction mixture was cooled to room temperature, quenched with saturated solution of Na2S2O3 (20 mL) and the reaction was extracted with ethyl acetate (3x 20 mL). The combined organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using Petroleum ether as eluent to provide 3a-u and 5a-g. | |
With selenium(IV) dioxide | ||
With iodine; dimethyl sulfoxide at 110℃; Sealed tube; | ||
With iodine; dimethyl sulfoxide; trifluoroacetic acid at 130℃; for 3h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With piperidine In ethanol for 2.5h; Reflux; | General method for preparation of compounds 11-31 General procedure: Solution of equimolar amounts of derivatives 1-3, corresponding heteroaromatic aldehydes 4-10 and few drops of piperidine in absolute ethanol, was refluxed for 1.5-2.5 h. After reaction mixture was cooled to the room temperature, the crude product was filtered off and recrystallizedfrom ethanol or separated by column chromatographyon SiO2. |
72% | With piperidine In ethanol for 2.5h; Reflux; | General method for preparation of compounds 11-31 General procedure: Solution of equimolar amounts of derivatives 1-3, corresponding heteroaromatic aldehydes 4-10 and few drops of piperidine in absolute ethanol, was refluxed for 1.5-2.5 h. After reaction mixture was cooled to the room temperature, the crude product was filtered off and recrystallizedfrom ethanol or separated by column chromatographyon SiO2. |
With piperidine; ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With manganese(IV) oxide In dichloromethane Reflux; | Benzothiazole-2-carbaldehyde (5) A mixture of benzothiazol-2-ylmethanol (0.33 g, 1.0 mmol) and manganese dioxide (1.70 g, 10 mmol) was treated with DCM (40 mL), and the reaction mixture was stirred under reflux for 15 h. The reaction progress was followed by TLC. After the solution had cooled to r.t., the mixture was filtered with diatomite and the filtrate was evaporated in vacuo to give compound 5 as: Brown solid; yield 92%; m.p. 73 °C (lit.32 75-76 °C); IR (KBr) (ν cm-1): 3057, 2846, 2354, 1694, 1485, 1204, 775; 1H NMR (500 MHz, DMSO-d6): δ 10.11 (s, 1H), 8.27 (dt, J = 7.3, 2.1 Hz, 2H), 7.71-7.62 (m, 2H). |
57.2% | With Dess-Martin periodane In dichloromethane at 20℃; for 1h; | 9.2 Step 2 Preparation of Intermediate 12 The intermediate 11 (2.0 g, 12.11 mmol) was dissolved in dichloromethane, and then added to the Dess-Martin reagent (6.2 g, 14.53 mmol), and reacted at room temperature for 1 h, and the reaction was completed by TLC.Then, 20 mL of saturated sodium hydrogencarbonate and 20 mL of saturated sodium thiosulfate were added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour, and then extracted with dichloromethane, and the organic layer was washed with brine and dried over Na 2SO 4 overnight. The desiccant was filtered off and concentrated under reduced pressure to give a red brown matter, column chromatography on a kind of white solid 1.13 g, yield 57.2. |
56% | With Dess-Martin periodane In dichloromethane at 4℃; for 1h; |
40% | With phthalic acid dimethyl ester In dichloromethane at 4℃; for 1h; | 2.4. Synthesis of benzothiazole-2-carbaldehyde (compound 5) To a solution of benzothiazol-2-ylmethanol (1.650 g,10.000 mmol) in methylene chloride (40 mL) was added DMP(4.600 g, 31.000 mmol), and the reaction was allowed to proceedwith stirring at 4 °C for 1 h prior to being quenched with saturatedaqueous sodium thiosulfate solution. The subsequent mixture wasextracted three times with methylene chloride. The combined organic extracts were dried with anhydrous magnesium sulfate andconcentrated. The crude product was purified by chromatographyon a silica gel column, eluting with DCM/MeOH (100/1, v/v) to yieldthe product benzothiazole-2-carbaldehyde [41] (0.650 g,40%). 1HNMR (400 MHz, CDCl3, TMS): δH 10.18 (s, 1H), 8.25 (d, J = 7.6 Hz, 1H),8.02 (d, J = 7.6 Hz, 1H), 7.61 (m, 2H). 13C NMR (100 MHz, CDCl3) δC184.432, 164.377, 135.263, 127.359, 126.966, 124.728, 121.649. |
With selenium(IV) oxide | ||
66 %Spectr. | With iodine; oxygen; trifluoroacetic acid In ethyl acetate at 70℃; for 20h; Irradiation; | |
1.09 g | With manganese(IV) oxide In dichloromethane at 45℃; for 12h; | 1 Example 1: 2-Hydroxymethylbenzothiazole (1.16 g, 7.0 mmol) was dissolved in 40 mL of dichloromethane,Manganese dioxide (4.87 g, 56 mmol) was added,45 reflux reaction 12h,Set aside cooling,Filtered to remove insoluble impurities,Concentrated, recrystallized from ethanol,1.09 g of solid benzothiazole-2-carbaldehyde was obtained. |
With Dess-Martin periodane In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: benzothiazole-2-carbaldehyde; bis(benzimidazol-2-ylmethyl)amine With acetic acid In tetrahydrofuran for 1h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 20℃; for 48h; Inert atmosphere; | Synthesis of (BimH)2(Bth) -“2N1S Ligand The ligands were synthesised using a modified version of the conditions detailed by V. O. Rodionov et.al. ( J . Am. Chem. Soc., 129 (42), (2007), 12696-704). H(BimH)2 (0.963 g, 2.5 mmols) and 2-benzothiazolecarboxaldehyde (0.429 g, 2.63 mmols) were dissolved in 50 ml dry THF forming a clear brown solution. Glacial acetic acid (0.6 g, 10 mmols) was added and the solution was stirred for one hour. Sodium triacetoxyborohydride (1.06 g, 5 mmols) was added and the solution was left stirring under nitrogen at room temperature. After 48 hours, the clear brown solution became an opaque light brown solution. The reaction mixture was transferred to a separating funnel containing 50 ml water and 50 ml DCM. The aqueous layer was extracted twice more with 50 ml DCM and the combined organic fractions were extracted once with 50 ml water. The solvent was rotary evaporated and the crude product was purified by column chromatography (1 % MeOH in DCM) on an alumina column producing a yellow/ orange solid. Yield 56%. dH/ppm (400 MHz, DMSO) 12.45 (s, 2H), 8.06 (dd, J=1.2 and 7.8 Hz, 1 H), 7.94 (dd, J=1.2 and 7.8 Hz, 1 H), 7.60-7.40 (m, 6H), 7.19-7.15 (m, 4H), 4.39 (s, 2H), 4.22 (s, 4H); m/z (ES-ToF); 425.16 ([M + H]+). |
With thionyl chloride; sodium cyanoborohydride In methanol for 10h; | ||
With thionyl chloride; sodium cyanoborohydride In methanol at 0℃; Inert atmosphere; | 7 (BimH)2 (0.693 g, 2.5 mmol) and aldehyde 5 (0.429 g, 2.63 mmol) were dissolved in dry methanol (10 mL). The solution was cooled to 0 0C and SOCl2 (30 μL) was added, followed by NaBH3CN (0.630 g, 10 mmol). The reaction mixture was stirred under N2 for10 hours, after which it was transferred to a separatory funnel containing 50 mL water and 50 mL CH2Cl2. The aqueous layer was extracted twice more with CH2Cl2 (50 mL) and the combined organic fractions were extracted once with water (50 mL), and then dried over MgSO4. The solvent was removed by rotary evaporation and the crude product was purified by chromatography (2% MeOH in CH2Cl2) on a short Florisil column. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With hydrogenchloride; water In tetrahydrofuran; hexane at 20℃; | 20 INTERMEDIATE 20; Benzothiazole-2-carboxaldehyde To a solution of benzothiazole (145 g, 1.07 mol) in dry THF (1 L) was added dropwise a solution of n-butyllithium in hexane (1.6 M, 700 mL, 1.12 mol) at-80 °C with stirring. The mixture was stirred for 30 min AT-80 °C, and a solution of DMF (100 ML, 1.7 mol) in THF (100 ML) was added dropwise AT-80 °C. The reaction mixture was warmed to room temperature, treated with concentrated HC1 (120 mL), and the organic layer was separated, dried over potassium carbonate, concentrated in vacuo, and the residue was recrystallized from ethanol to provide the title compound (70%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | EXAMPLE 34 Synthesis of 2-benzothiazolecarbaldehyde-(5-cyano-2-pyridyl)hydrazone (compound 34) A desired product was obtained in the same manner as in Example 1 by using 2.70 g (20.1 mmol) of <strong>[104408-24-4]5-cyano-2-pyridylhydrazine</strong> and 3.40 g (20.8 mmol) of 2-benzothiazolecarbaldehyde. Yield: 4.70 g (16.8 mmol) [yield rate: 84%] Melting point: 253 to 254 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: 1,3-Benzothiazole; N,N-dimethyl-formamide With tris(trimethylsilyl)amine; tetramethylammonium fluoride at 20℃; for 19h; Inert atmosphere; Sealed tube; Stage #2: With hydrogenchloride In water at 20℃; for 1.5h; | |
53% | Stage #1: 1,3-Benzothiazole With n-butyllithium In tetrahydrofuran at -84℃; for 1h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -84℃; for 4h; Inert atmosphere; | |
50% | Stage #1: 1,3-Benzothiazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -78℃; for 4.5h; Inert atmosphere; |
37% | Stage #1: 1,3-Benzothiazole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran at -78 - 20℃; for 2h; Stage #3: With water; ammonium chloride In tetrahydrofuran | 1.5 Intermediate 5: l,3-Benzothiazole-2-carbaldehyde[0455] ft-BuLi (2.5 M, 5.2 mL, 13 mmol) was added to a solution of benzo[4CI solution was added and the resulting mixture was extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous Na2S04 and concentrated to afford 612 mg of the title compound as a yellow solid (37% yield). |
Stage #1: 1,3-Benzothiazole With n-butyllithium In diethyl ether at -78℃; for 1h; Stage #2: N,N-dimethyl-formamide In diethyl ether at 0 - 20℃; for 3h; | ||
With n-butyllithium at -78℃; for 1.25h; | 14.j (j ) B enzo [d] thiazole-2-carbaldehyde[00396] To a solution of benzo[d]thiazole (1 g, 7 mmol) in DMF (10 mL) was added «-BuLi (8.4 mL, 21 mmol) over 15 min at -78 °C and the mixture was stirred at this temperature for 1 hour. The reaction was quenched with water, extracted with EtOAc and dried over anhydrous sodium sulfate. The solution was then concentrated under vacuum to give benzo[d]thiazole-2- carbaldehyde as a light yellow solid (500 mg). | |
Stage #1: 1,3-Benzothiazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane | 1 2.3.1 Synthesis of benzothiazole-2-carboxaldehyde (btzca) Benzothiazole-2-carboxaldehyde was synthesized using a previously reported procedure [36] from benzothiazole by eliminating of the proton in the position 2 with n-BuLi, followed by a neutralization. A solution of nBuLi in hexane (2 mL, 2 M) was slowly added to a solution of benzothiazole (0.5023 g, 3.7 mmol) in dry THF (5mL) at -78 °C. Then a solution DMF in THF (18.5 mmol, 1.4 mL) was dropped into the mixture and finally neutralized. A yellow powder was obtained. The product was purified by a chromatography column with an AcOEt-hexane solution (1:50). Needle crystals were obtained by re-crystallization with dichloromethane. After the purification, this precursor was characterized by 1H NMR (400 MHz, CDCl3): δ 10.17 (s, 1H), 8.25 (ddd J = 9.5, 6.6, 5.2, 0.7 Hz, 1H), 8.00 (ddd, J = 9.4, 6.3, 5.0, 0.7 Hz, 1H), 7.59 (dqd, J = 7.9, 7.2, 1.5 Hz, 2H), 7.57 (s, 1H) and 7.62 (s, 1H) Fig. SI 2. 13C NMR (400 MHz, CDCl3): δ = 185, 165, 153, 136, 122, 125, 127 and 128. Fig. SI 3 MS(ESI): m/z = 163. | |
Stage #1: 1,3-Benzothiazole With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -60℃; for 1h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; n-heptane; ethylbenzene at -60℃; for 0.5h; Cooling with ice; | Typical experimental procedure for one-pot preparation of aryl or heteroaryl-bearing acrylates (4).Methyl (E)-3-(benzo[b]thiophen-2-yl)acrylate (4a):6 (Table 1, entry 2) General procedure: To a solution of 3a (161 mg, 1.20 mmol) in THF (4.0 mL) was added dropwise lithium diisopropylamide(1.93 M solution in THF/heptane/ethylbenzene, 0.68 mL, 1.3 mmol) at dry ice-acetone bath temperaturewith stirring for 1 h. To the solution was added dropwise DMF (0.10 mL, 1.3 mmol), and the reactionmixture was allowed to warm to ice-bath temperature and stirred for 30 min. Trimethyl phosphonoacetate(0.21 mL, 1.5 mmol) was added and stirring at ice-bath temperature was continued for 1 h. Aqueous 5%HCl (2 mL) and water (4 mL) were added successively and the mixture was extracted with EtOAc (10mL). The organic layer was separated and washed with water (10 mL), dried over anhydrous sodiumsulfate, and concentrated. The residual oil was subjected to column chromatography (silica gel) to give 4a(229 mg, 87%) as a white solid; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | Benzothiazole-2-carbaldehyde (39b); A solution of 39a in CH2Cl2 (10 mL) was cooled down to -50 0C and a 1.0 M solution of DIBAL-H in hexanes (1.5 mL, 1.5 mmol) was then added slowly dropwise. When the addition was completed the reaction mixture was warmed up to r.t. and carefully quenched with EtOAc and 2 M HCl. The product was extracted into CH2Cl2, dried (Na2SO4) and evaporated to give an orange oil that was purified by flash chromatography on silica gel (Hep:EtOAc 10:1) to give 25 mg (11%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5% | Stage #1: benzothiazole-2-carbaldehyde; 5-(2,6-dimethoxyphenyl)-1,2,4-triazin-3-amine In tetrahydrofuran; 1,2-dichloro-ethane at 35℃; Inert atmosphere; Molecular sieve; Stage #2: With sodium tetrahydroborate In tetrahydrofuran; methanol; 1,2-dichloro-ethane at 35℃; for 4h; | 4 Under argon, a solution of 5-(2,6-dimethoxyphenyl)-1,2,4-triazin-3-amine (30 mg, 0.13 mmol) and 1,3-benzothiazole-2-carbaldehyde (42 mg, 0.26 mmol) in 1,2-dichloroethane (0.7 mL) and THF (0.3 mL) with 4Å molecular sieves was stirred overnight at 35°C. Sodium borohydride (15 mg, 0.4 mmol) and methanol (0.2 mL) were then added and the reaction mixture was stirred for 4 hours at 35°C. The solution was filtered and the filtrate was concentrated. Dichloromethane and water were added, the resulting mixture was extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and evaporated. Purification by preparative TLC (silica gel, dichloromethane/methanol 95/5) afforded N-(1,3-benzothiazol-2-ylmethyl)-5-(2,6-dimethoxyphenyl)-1,2,4-triazin-3-amine (2.5 mg, 5%) as a white solid. ESI-MS m/z 380 (M+H)+. 1H NMR (CDCl3), δ (ppm): 8.61 (s, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.48-7.45 (m, 1H), 7.40-7.35 (m, 2H), 6.62 (d, J = 8.0 Hz, 2H), 5.20 (d, J = 5.2 Hz, 2H), 3.70 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Stage #1: benzothiazole-2-carbaldehyde; N-BOC-1,2-diaminoethane In methanol at 20℃; Inert atmosphere; Stage #2: With sodium tetrahydroborate In methanol at 20℃; for 2h; | 92.a Under argon, a solution of 1,3-benzothiazole-2-carbaldehyde (49 mg, 0.30 mmol) and tert-butyl 2-aminoethylcarbamate (50 mg, 0.31 mmol) in methanol (1.2 mL) was stirred at room temperature overnight. Sodium borohydride (11.4 mg, 0.30 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours. The mixture was concentrated and the residue was purified by preparative TLC (silica gel, dichloromethane/methanol 9/1) to furnish tert-butyl 2-[(1,3-benzothiazol-2-ylmethyl)amino]ethylcarbamate (57.1 mg, 62%) as a pale yellow oil. ESI-MS m/z 308 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Stage #1: benzothiazole-2-carbaldehyde; propan-1-ol-3-amine In methanol at 20℃; Inert atmosphere; Stage #2: With sodium tetrahydroborate In methanol at 20℃; for 1.5h; Stage #3: With water; ammonium chloride In methanol | 89.a Under argon, a solution of 1,3-benzothiazole-2-carbaldehyde (31.4 mg, 0.19 mmol) and 3-aminopropan-1-ol (16 µL, 0.21 mmol) in methanol (1 mL) was stirred at room temperature overnight. Sodium borohydride (7 mg, 0.19 mmol) was added and the reaction mixture was stirred at room temperature for 1.5 hours. A few drops of aqueous ammonium chloride were added and the mixture was filtered over a pad of celite and concentrated. The residue was purified by preparative TLC (silica gel, dichloromethane/methanol 9/1) to furnish 3-[(1,3-benzothiazol-2-ylmethyl)amino]propan-1-ol (19.1 mg, 45%) as a pale yellow oil. ESI-MS m/z 223 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 25℃; for 2h; | 144.1 Step 1: methyl 3-(benzo[d]thiazol-2-yl)-2-(tert-butoxycarbonylamino)acrylate A solution of methyl [(tert-butoxycarbonyl)amino](dimethoxyphosphoryl)acetate (Fluka, Cat. #09659) (194 mg, 651 μmol), benzo[d]thiazole-2-carbaldehyde (VWR, Cat. #100605-032) (80 mg, 543 μmol), methylene chloride (2.26 ml, 35.2 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (97.4 μl, 651 μmol) was stirred at 25° C. for 2 h. The reaction was taken up in ethyl acetate, washed with 1 N HCl, brine, dried over magnesium sulfate and concentrated under reduced pressure to give the crude product as an oil. The product was purified by Flash chromatography on a silica gel column eluding hexane: ethyl acetate gradient to give a mixture of methyl 3-(benzo[d]thiazol-2-yl)-2-(tert-butoxycarbonylamino)acrylate (0.18 g, 98%) as a clear oil. Analytical LCMS (M+H)+: m/z=334.9. |
Yield | Reaction Conditions | Operation in experiment |
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Stage #1: benzothiazole-2-carbaldehyde; 3-pent-4-enyloxy-phenylmagnesium bromide In tetrahydrofuran at -50 - 20℃; Stage #2: With ammonium chloride In tetrahydrofuran; water | 168B 168BBenzothiazol-2-yl(3-pent-4-enyloxy-phenyl)methanol can be prepared as follows: to a 1 M solution of 3-pent-4-enyloxy-phenylmagnesium bromide in tetrahydrofurane (2.2ml_) diluted with the same solvent (6ml_) cooled at -50°C is added benzothiazole-2- carboxaldehyde (326mg). After stirring at -50°C for 1 h, the mixture is allowed to warm at room temperature, then hydrolyzed with aqueous saturated ammonium chloride solution and extracted with ethyl acetate. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography (gradient heptane / ethyl acetate from 4 / 1 to 2 / 1 ) to give benzothiazol- 2-yl(3-pent-4-enyloxy-phenyl)methanol as a yellow oil. | |
Stage #1: benzothiazole-2-carbaldehyde; 3-pent-4-enyloxy-phenylmagnesium bromide In tetrahydrofuran at -50℃; for 1h; Stage #2: With ammonium chloride In tetrahydrofuran; water at 20℃; | 168.168B Benzothiazol-2-yl(3-pent-4-enyloxy-phenyl)methanol can be prepared as follows: to a 1M solution of 3-pent-4-enyloxy-phenylmagnesium bromide in tetrahydrofurane (2.2mL) diluted with the same solvent (6mL) cooled at -50°C is added benzothiazole-2-carboxaldehyde (326mg). After stirring at -50°C for 1h, the mixture is allowed to warm at room temperature, then hydrolyzed with aqueous saturated ammonium chloride solution and extracted with ethyl acetate. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography (gradient heptane / ethyl acetate from 4 / 1 to 2 / 1) to give benzothiazol-2-yl(3-pent-4-enyloxy-phenyl)methanol as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium carbonate; In methanol; water; at 130℃; for 0.5h;Microwave irradiation; | General procedure: In a microwave reaction vial with a magnetic stirring bar was placed the azaindoleor indole (0.38 mmol), aldehyde (0.19 mmol), and K2CO3 (176 mg, 1.27 mmol), followedby addition of 2.5 mL of 1:1 mixture of MeOH:H2O. The resulting mixture was placed ina microwave reactor and irradiated at 130 oC for 30 minutes. After cooling to roomtemperature, the volatiles were removed under reduced pressure. The crude residue wasdiluted with water (10 mL) and extracted with ethyl acetate (3 x 10 mL). The combinedorganic layers were dried over sodium sulfate, filtered, and the resulting filtrate evaporated in vacuo to give a crude solid that was purified using reversed-phase HPLC,eluting with MeCN/H2O with a trace of TFA to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | Stage #1: benzothiazole-2-carbaldehyde; 5-bromo-2-(5-bromoindolin-2-yl)-3-fluorophenol In acetonitrile at 80℃; for 15h; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In toluene at 100℃; for 2h; | 27.1 Example 27 To a stirring solution of Int-lb (0.5 g, 1.29 mmol) in ACN (6.0 mL) was added 2-(pyrazin-2-yl)thiazole-5-carbaldehyde (450 mg, 2.0 eq), MP-TsOH (0.5 g, 2 eq). The resulting mixture was heated to 80 °C for about 15 hours. The reaction was monitored using LCMS. After dilution with DCM followed by filtration and rinced with DCM, the resulting filtrate was concentrated in vacuo. The residue was taken up in toluene and was further treated with DDQ at 100°C for 2 h and after this period the reaction mixture was cooled to room temperature, diluted with EtOAc,washed with aq-NaHC03 soln and brine, dried over Na2S04, filtered, concentrated in vacuo. The crude material was purified over Si02 column (0 to 100% EtOAc containing 0.5% DEA/Hex) to provide compound 401a (0.15 g, 15%) as a light brown solid. 1H MR (CDC13, 500MHz) δ: 8.07 (d, J=8.0 Hz, 1H), 7.87 (s, 1H ), 7.76 (d, J=8.0 Hz, 1H), 7.64 (s, 1H), 7.53-7.50 (m, 1H), 7.43-7.378 (m, 2H), 7.30-7.28 (m, 1H), 7.19 (s, 1H), 7.16-7.15 (m, 2H). M+l : 531 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With hydroxylamine hydrochloride; sodium carbonate In methanol; water at 20℃; for 5h; | 1.1 Step 1: Benzothiazole-2- formaldehyde (1.63 g, 10 mmol), hydroxylamine hydrochloride (1·04 g, 15 mmol) was placed in a round bottom flask, 100 ml of 50% aqueous methanol was added, 6 ml of sodium carbonate aqueous solution (0.75 M) was added with stirring, after the addition was completed, the reaction was stirred at room temperature for 5 hours, and dried, separation and purification by silica gel column chromatography to obtain a solid powder in a yield of 87%. |
78% | With hydroxylamine hydrochloride; sodium hydroxide In ethanol; water at 20℃; for 4h; | 6B Example 6B - benzorblthiazole-2-carbaldehyde oxime (B-106) To a mixture of benzo[b]thiazole-2-carbaldehyde (2.0 g, 12.3 mmol) and hydroxylamine hydrochloride (1.3 g, 18.5 mmol) in ethanohwater (9: 1 , 20 mL) was added sodium hydroxide (1.0 g, 24.6 mmol) at room temperature. The mixture was stirred at room temperature for 4 h. On completion, two isomers were observed on TLC. After concentration, the mixture was extracted with dichloromethane (10 mL x 2). The combined organic layers were washed with water, brine and then dried over sodium sulfate. After concentration the two spots was separated by silica chromatography (petroleum ether / ethyl acetate = 10 : 1). The higher running spot was isolated to give compound B-106 as a white solid (1.5 g, 78 % yield) and was used for next step. LCMS: (ES+) m/z (M+H)+ = 178.9, tR=0.852. |
8% | With hydroxylamine hydrochloride; sodium carbonate In ethanol; water for 0.333333h; Reflux; Inert atmosphere; | General procedure A2 for the synthesis of aromatic aldoximes General procedure: An aldehyde (3.24 mmol) was dissolved in EtOH (12 mL), then a solution of NH2OH*HCl (360 mg, 5.18 mmol) and Na2CO3 (247 mg,2.33 mmol) in water (3 mL) was added, and the mixture was boiled at reflux temp for 20 min. Saturated aqueous NaCl solution (30 mL)was added, and the mixture was extracted by EtOAc (2 20 mL).The combined organic layers were dried (MgSO4) and evaporated to give the expected aldoxime which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium tetrahydroborate In methanol at 0 - 20℃; for 2h; Inert atmosphere; | 2-(Hydroxymethyl)benzothiazole (2) According to the Attardo’s method1, to a solution of benzothiazole-2-carboxaldehyde (1) (500 mg, 3.06 mmol) in dist. MeOH (20 mL) was added sodium borohydride (162 mg, 4.23 mmol) at 0 °C. The reaction mixture was stirred at room temperature under argon for 2 hours. Saturated NH4Cl solution (10 mL) was added. The methanol was removed under reduced pressure. The resultant mixture was extracted with EtOAc (3 x 40 mL) and CH2Cl2 (40 mL). The organic phase was combined, dried over Na2SO4, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2 : MeOH = 15 : 1) to give 22 (506 mg, 100%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 3.91 (t, 1H, J = 5.5 Hz), 5.07 (d, 2H, J = 5.5 Hz), 7.37 (dt, 1H, J = 8.1 Hz, 1.1 Hz), 7.46 (dt, 1H, J = 8.1 Hz, 1.1 Hz), 7.87 (dd, 1H, J = 8.1 Hz, 1.1 Hz), 7.97 (dd, 1H, J = 8.1 Hz, 1.1 Hz). 13C NMR (75 MHz, CDCl3) δ 62.5, 121.8, 122.7, 125.1, 126.2, 134.7, 152.7, 172.6. MS (EI) 165 (M)+. TLC: Rf 0.35 (CH2Cl2 : MeOH= 15 : 1). |
100% | With sodium tetrahydroborate In methanol at 0 - 20℃; for 2h; Inert atmosphere; | 2-(Hydroxymethyl)benzothiazole (2) Benzothiazole-2-carboxaldehyde (1) (500 mg, 3.06 mmol) was dissolved in dist. MeOH (20 mL) and cooled to 0°C. Sodium borohydride (162 mg, 4.28 mmol) was added, and the mixture was stirred at room temperature for 2 hours under an argon atmosphere. Then, saturated NH4Cl solution (10 mL) was added, and methanol was removed by concentration under reduced pressure. The residue was extracted with EtOAc (3 x 40 mL) and CH2Cl2 (40 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography (CH2Cl2:MeOH=15:1) gave compound 2 (506 mg, 100%) as a white solid. 1H NMR (300MHz, CDCl3) δ 3.91 (t, 1H, J = 5.4Hz), 5.07 (d, 2H, J = 5.4Hz), 7.37 (td, 1H, J = 8.1Hz, 1.1Hz), 7.46 (td, 1H, J = 8.1Hz, 1.1Hz), 7.87 (dd, 1H, J = 8.1Hz, 1.1Hz), 7.97 (dd, 1H, J = 8.1Hz, 1.1Hz). 13C NMR (75MHz, CDCl3) δ 62.5, 121.8, 122.7, 125.1, 126.2, 134.7, 152.7, 172.6. EI-MS (m/z) 165 [M]+. TLC: Rf 0.35 (CH2Cl2:MeOH=15:1). |
98% | With sodium tetrahydroborate In ethanol at 20℃; for 20h; |
With sodium tetrahydroborate In ethanol at 0 - 20℃; Inert atmosphere; | ||
With sodium tetrahydroborate; ethanol at 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With pyrrolidine In acetonitrile at 20℃; for 1h; Inert atmosphere; | 6 Example 6 (0181) (£ -H-(2-(benzo[d]thiazol-2-yl)vinyI)-6,7-dimethyl-4,5,8,9-tetrahydroisoquinoIino[l,2- a]pyrido[l,2-k] [2,9]phenanthroline-3,10-diium trifluoromethanesulfonate, VDJA-C8-5 Example 6 (0181) (£ -H-(2-(benzo[d]thiazol-2-yl)vinyI)-6,7-dimethyl-4,5,8,9-tetrahydroisoquinoIino[l,2- a]pyrido[l,2-k] [2,9]phenanthroline-3,10-diium trifluoromethanesulfonate, VDJA-C8-5Starting racemic helquat B (20 mg, 29.6 μηιο), benzo[d]thiazole-2-carbaldehyde (121 mg, 739 μπιο), pyrrolidine (30 μ, 367.2 μπιο) and dry acetonitrile (2 ml) were placed into a 10 ml flask and the resulting mixture was stirred under argon for 1 h at room temperature. Progress of the reaction was monitored by thin layer chromatography. The crude product was precipitated from the reaction mixture by addition of diethylether (16 ml). The suspension was centrifuged and the supernatant was separated from the solid pellet. The solids were dissolved in methanol (2 ml) and the pure product was precipitated by addition of diethylether (12 ml). Then, centrifugation of this suspension, removal of the supernatant and drying of the solid part under vacuum of an oil pump led to 14 mg (17.0 μηιο, 58 % yield) of an orange solid VDJA-C8-5. 3- (0183) (0184) NMR (400 MHz, acetone-d6): 2.67 (s, 3H), 2.68 (s, 3H), 3.49-3.54 (m, 2H), 3.82 (dq, J = 1.7, 17.1 Hz, 1H)5 3.89 (dq, J= 1.7, 17.1 Hz, 1H), 5.17 (dt, J= 3.4, 14.6 Hz, 1H), 5.33 (dt, .7= 3.7, 14.0 Hz, 1H), 5.40 (dd, J= 1.6, 13.9 Hz, 1H), 5.75 (dd, J= 1.6, 13.9 Hz, 1H), 7.61 (dt, J= 1.2, 7.2 Hz, 1H), 7.64 (dt, J = 1.3, 8.2 Hz, 1H), 7.69 (dt, J = 1.3, 7.2 Hz, 1H), 7.88 (dt, J = 1.2, 6.8 Hz, 1H), 7.91 (t, j = 8.1 Hz, 1H), 8.00 (d, J= 15.8 Hz, 1H), 8.02 (t5 J= 1.2 Hz, 1H), 8.17 (dq, J= 0.7, 8.1 Hz, 1H), 8.18 (dd, J= 0.8, 8.7 Hz, 1H), 8.22 (dq, J= 0.7, 8.1 Hz, 1H), 8.24 (dd, J= 1.3, 8.1 Hz, 1H), 8.31 (d, J= 9.2 Hz, 1H), 8.41 (d, J= 15.9 Hz, 1H), 8.58 (d, J= 6.7 Hz, 1H), 9.06 (d, J= 6.7 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With sodium sulfate In methanol at 20℃; | General procedure for the synthesis of α,β-unsaturated γ-lactams General procedure: To a solution of aldehydes (1a-g, 1 equiv) in methanol (3 mL) were added successively Na2SO4 (0.3 g), amines (2a-f, 1.2 equiv), 2-alkynoic acids (3a-d, 1.2 equiv) and isonitriles (4a-e, 1.2 equiv) in a screw capped vial equipped with a magnetic stir bar. The reaction mixture was stirred at room temperature or 50 °C for 24-48 hours in closed vial. After completion of the reaction, the mixture was diluted with dichloromethane (50 mL) and was extracted with water (50 mL). Organic layer was washed with brine (50 mL), dried over magnesium sulfate and evaporated under reduced pressure to obtained residue which was subjected to silica gel column chromatography to afford the desired product α,β-unsaturated γ-lactams (5a-s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium sulfate; In methanol; at 20℃; | General procedure: To a solution of aldehydes (1a-g, 1 equiv) in methanol (3 mL) were added successively Na2SO4 (0.3 g), amines (2a-f, 1.2 equiv), 2-alkynoic acids (3a-d, 1.2 equiv) and isonitriles (4a-e, 1.2 equiv) in a screw capped vial equipped with a magnetic stir bar. The reaction mixture was stirred at room temperature or 50 C for 24-48 hours in closed vial. After completion of the reaction, the mixture was diluted with dichloromethane (50 mL) and was extracted with water (50 mL). Organic layer was washed with brine (50 mL), dried over magnesium sulfate and evaporated under reduced pressure to obtained residue which was subjected to silica gel column chromatography to afford the desired product alpha,beta-unsaturated gamma-lactams (5a-s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium sulfate In methanol at 20℃; | General procedure for the synthesis of α,β-unsaturated γ-lactams General procedure: To a solution of aldehydes (1a-g, 1 equiv) in methanol (3 mL) were added successively Na2SO4 (0.3 g), amines (2a-f, 1.2 equiv), 2-alkynoic acids (3a-d, 1.2 equiv) and isonitriles (4a-e, 1.2 equiv) in a screw capped vial equipped with a magnetic stir bar. The reaction mixture was stirred at room temperature or 50 °C for 24-48 hours in closed vial. After completion of the reaction, the mixture was diluted with dichloromethane (50 mL) and was extracted with water (50 mL). Organic layer was washed with brine (50 mL), dried over magnesium sulfate and evaporated under reduced pressure to obtained residue which was subjected to silica gel column chromatography to afford the desired product α,β-unsaturated γ-lactams (5a-s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With aluminium(III) chloride hexahydrate In ethanol for 24h; Reflux; | 2-(benzothiazole)-2,3-dihydro-1H-perimidine(bzpm) Thetitled compound was prepared from a 1:1 molar condensation reaction betweenbenzothiazole-2-carboxaldehyde (0.1928 g, 1.182 mmol) and 1, 8-diaminonaphthalene(0.187 g, 1.182 mmol) in 20 cm3 of absolute ethanol. The catalystemployed was AlCl3.6H2O (0.028 g, 0.118 mmol). The resultantreaction mixture was heated until reflux for 24 hrs. Afterwards, the volume ofa dark brown solution was reduced using a rotary-evaporator and a dark brownprecipitate was filtered off. This precipitatewas purified via columnchromatography using a 6:4 (v:v)ethyl acetate:hexane solvent system to produce a brown precipitate. M.P.= 140-143C, yield = 70%. IR (νmax/cm-1): ν(N-H)3442, 3307 (m); ν(C=N) 1595 (s). 1H NMR (295K/ ppm): 8.00 - 7.94 (m,2H, H5, H8); 7.52 - 7.45 (t, 2H, H6,H7); 7.43 - 7.34 (m, 2H, H14, H18);7.21 (t, 2H, H13, H19); 7.05 (d, 2H, H15, H17); 6.60 (d, 2H, N2H, N3H); 5.93 (s, 1H, H11). UV-vis(DCM, (λmax(ε, M-1cm-1))):316 nm (7874); 338 nm (sh, 7548); 393 nm (sh, 2461). HRMS: found[M++Na] 326.0723, calculated for C10H13N3NaS= 326.0728. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With piperidine In methanol for 3h; Reflux; | 1 N-[1,3-benzothiazol-2-ylmethylidene]pyridine-2-carbohydrazide (bzpc) The 1:1 molar condensation reaction between benzothiazole-2-carbaldehyde (0.18 g, 1.09 mmol) and pyridine-2-carbohydrazide (0.15 g, 1.09 mmol) was conducted in 20 cm3 of MeOH heated until reflux for 3 hours in the presence of a catalytic amount of piperidine. The resultant yellow solution was reduced to 5 cm3 and allowed to cool to room temperature. A light yellow, crystalline precipitate was filtered and washed with 3 cm3 of cold MeOH and 6 cm3 of petroleum ether. Yield: 0.23 g (75%). M.P: 204.3 - 209.2 °C. IR (νmax/cm-1): v(N-H) 3262 w, v(C=O) 1683 s, v(C=N) 1519 s, v(C-S) 762 m. 1H NMR (303K/ppm): 12.84 (s, 1H, NH), 9.00 (s, 1H, H10), 8.76 (ddd, 1H, H4), 8.14-8.18 (m, 2H, H7, H16), 8.07-8.11 (m, 1H, H5), 8.05-8.08 (m, 1H, H13), 7.72 (ddd, 1H, H6), 7.54-7.58 (m, 1H, H15), 7.50-7.54 (m, 1H, H14). UV-Vis (MeOH, λmax (ε, M-1cm-1)): 326 nm (17280), 352 nm (15045). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogenchloride In ethanol; water at 80℃; for 4h; | 4.1.1. General Procedure for the Automated Synthesis of Compounds 1-5 General procedure: Aldehyde (1.00 mmol), hydrazide (1.00 mmol), ethanol (4.0 mL) and 50 L of aqueous 1M HClwere added in a 13 mL double jacket reactor from Chemspeed equipped with condenser. The mixturewas shaken at 700 rpm for 4 h at 80 °C, then cooled down to 20 °C. The precipitate was filtrated andsuccessively washed with 2 mL of ethanol and 2 mL of ethyl ether to obtain the product. |
72% | In methanol for 3h; Reflux; | 2 N-[1,3-benzothiazol-2-ylmethylidene]thiophene-2-carbohydrazide} (bztc) Equimolar amounts of 1,3-benzothiazole-2-carbaldehyde (0.17 g, 1.05 mmol) and thiophene-2-carbohydrazide (0.15 g, 1.05 mmol) were reacted in 20 cm3 of MeOH for 3 hours under reflux conditions. The yellow solution was allowed to cool to room temperature. Cream coloured precipitate was filtered and washed with 3 cm3 of cold MeOH and 3 cm3 of petroleum ether. Yield: 0.22 g (72%). M.P: 212.2 - 215.9 °C. IR (νmax/cm-1): v(N-H) 2851 w, v(C=O) 1651 s, v(C=N) 1584 m, v(C-S) 728 s. 1H NMR (303K/ppm): 12.35 (br s, 1H, NH), 8.70 (br s, 0.5H, H1), 8.44 (br s, 0.5H, H1), 8.15 (d, 1H, H5), 8.05 (d, 1H, H2), 7.84-8.23 (v br s, 2H, H7, H8), 7.54-7.57 (m, 1H, H4), 7.49-7.52 (m, 1H, H3), 7.25-7.27 (m, 1H, H6). UV-Vis (MeOH, λmax (ε, M-1cm-1)): 327 nm (28800), 355 nm (29101). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With acetic acid In ethanol for 4h; Reflux; | 2.5. Synthesis of probe 1 A mixture of benzothiazole-2-carbaldehyde (1.630 g,1.000 mmol), 4-hydrazinehydrate-N-butyl-1,8-naphthalimide(0.283 g, 1.000 mmol) and a drop of acetic acid was heated toreflux for 4 h in 10 mL ethanol. After cooling to the room temperature,many precipitates formed. The precipitates were collectedthrough filtration and recrystallized from ethanol to give pale yellowprobe 1 (0.359 g, 84%). MP: 194.5-195.5 °C. 1H NMR (400 MHz,DMSO-d6, TMS): δH 12.05 (s, 1H), 8.78 (d, J = 8.4 Hz, 1H), 8.68 (s, 1H),8.52 (d, J = 7.2 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.87 (t, J = 8.4 Hz, 1H),7.73 (d, J = 8.4 Hz, 1H), 7.57-7.47 (m, 2H), 4.03 (t, J = 7.2 Hz, 2H),1.61 (m, 2H), 1.35 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H). IR (KBr: v (cm-1)):3445, 3222, 2960, 1682, 1647, 1587, 1566, 1387, 1242, 1120, 1020.HRMS (EI): m/z Calcd for C24H20N4O2S1 [M]-, 428.1307; found,428.1308. Anal. Calcd for C24H20N4O2S1: C, 67.27; H, 4.70; N, 13.07%.Found: C, 67.23; H, 4.66; N, 13.11%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In methanol at 45℃; for 3h; | 4′-(5-(benzothiazole-2-methyleneamino)pentanoxy)-2,2′:6′,2′′-terpyridine (bzterpy) Equimolar amounts of 1,3-benzothiazole-2-carbaldehyde (74 mg; 457 µmol) and tpa (64 mg; 457 µmol) were stirred for 3 hrs at 45 °C in 10 cm3 of MeOH. The resultant solution was boiled down to ~ 3 cm3 and allowed to cool to room temperature. Then a peach coloured precipitate was filtered and washed with cold MeOH and petroleum ether. XRD quality needle-shaped crystals were grown from a 1:1 (v:v) solution of MeOH: EtOH. Yield: 90%. M.P: 232.4 - 235.8 °C. IR (νmax/cm-1): v(N-H) 2952 w, v(C=N) 1557 s, v(C-O-C) 1196 m, v(C-S) 767 s. 1H NMR (298 K/ppm): 8.71 (dd, 2H, H1, H15), 8.66 (s, 1H, H21), 8.61 (dd, 2H, H27, H24), 8.10 (dt, 2H, H2, H14), 8.03-7.96 (m, 4H, H3, H7, H9, H13), 7.59-7.48 (m, 4H, H4, H12, H25, H26), 4.29 (t, 2H, H16, H16’), 3.78 (t, 2H, H20, H20’), 1.94-7.86 (m, 2H, H17, H17’), 1.85-1.76 (m, 2H, H19, H19’), 1.64-1.54 (m, 2H, H18, H18’). UV-Vis (MeOH, λmax (ε, M-1cm-1)): 241 nm (15277), 282 nm (22046). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With ammonium hydroxide; potassium hydroxide In ethanol at 20℃; for 6h; | 2-([2,2′:6′,2″-Terpyridin]-4′-yl)-1,3-benzothiazole(TP1). A solution of 1,3-benzothiazole-2-carbaldehyde(0.5 mmol, 81.5 mg) in 2 mL of ethanol wasadded to a solution of 2-acetylpyridine (1 mmol,121 mg) in 3 mL of ethanol. The mixture was stirred atroom temperature for 15 min, a small piece of KOHpellet (~0.05 mg) was added, 25% aqueous ammonia(1.5 mL) was then added, and the resultant mixture wasstirred at room temperature for 6 h. After completion ofthe reaction (TLC), the solid product was filtered offunder vacuum onto a sintered funnel, washed with icecoldethanol until colorless washings, and recrystallizedfrom chloroform. Yield 180 mg (98%), greenish whitesolid, mp 135-136°C. IR spectrum (KBr), ν, cm-1:1684, 1581, 1402, 1021. 1H NMR spectrum, δ, ppm:7.3 d.d (2H, J = 5.5, 7.0 Hz), 7.4 d.t (1H, J = 1.0,8.0 Hz), 7.5 d.t (1H, J = 1.5, 8.5 Hz), 7.9 d.t (2H, J =1.5, 7.5 Hz), 8.0 d (J = 8.0 Hz), 8.2 d (1H, J = 8.0 Hz),8.6 d (2H, J = 8.0 Hz), 8.8 d.d (2H, J = 1.0, 5.0 Hz),9.1 s (2H). 13C NMR spectrum, δC, ppm: 118.71,121.32, 121.86, 124.03, 124.09, 125.96, 126.61,135.52, 136.85, 142.68, 149.31, 154.13, 155.63,156.63, 165.78; DEPT-135, δC, ppm: 118.70, 121.33,121.86, 124.03, 124.10, 125.96, 126.61, 136.86,149.31. Mass spectrum (ESI): m/z 367.1005 [M + H]+.Calculated for C22H15N4S: 367.1012 |
With ammonium acetate; acetic acid; sodium hydroxide for 2h; Reflux; | 2.2.1.1. 4'-(1,3-benzothiophene)-2, 2':6',2''-terpyridine (Btptpy) (L1). General procedure: Ligand L1 has been synthesized by using kroneke pyridine synthesismethod. A mixture of 2-acetyl pyridine (5 mM) and Benzothiophene-2-carboxaldehydes (2.5 mM) was taken in a mortar andground well in the presence of NaOH. The resulting red powderwasrefluxed with ammonium acetate and acetic acid suspension 2 h. After cooling the solution to room temperature ice cold waterwas added. The resulting solid was filtered using successionfiltration and kept for drying in desiccator. Ligand was recrystallizedfrom chloroform. Fine crystals suitable for single crystal X-raydiffraction were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With piperidine In ethanol Reflux; | 4.3. General method for the preparation of imidazolylphenylheterocyclic-2-ylmethylene-thiazole-2-amines (4a-4i) General procedure: A mixture of substituted compound 3 (0.01 mol), substituted heterocyclic aldehyde (0.01 mol) and piperidine (0.01 mol) was refluxed in 30 mL ethanol for 6-8 h. The reaction mixture was poured into an ice-water mixture to get a product, which was filtered, dried, and recrystallized using ethanol to give the final compounds 4a-4i, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With piperidine In ethanol for 6h; Reflux; | Synthesis of (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones (6a-j); general procedure General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. (E)-3-(Benzothiazol-2-ylmethylene)indolin-2-one (6a): Dark red solid; yield 89%; m.p. 275-277 °C; IR (KBr) (ν cm-1): 3151, 3083, 2884, 1706, 1608, 1330, 1219, 1086, 741; 1H NMR (500 MHz, DMSO-d6): δ 10.78 (s, 1H), 9.23 (d, J = 7.7 Hz, 1H), 8.28 (d, J = 8.2 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.69-7.63 (m, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 7.7 Hz, 1H). HRMS (EI) m/z calcd for C16H10N2OS (M+): 278.0514; found: 278.0512. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With piperidine In ethanol for 6h; Reflux; | Synthesis of (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones (6a-j); general procedure General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With piperidine In ethanol for 6h; Reflux; | Synthesis of (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones (6a-j); general procedure General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With piperidine In ethanol for 6h; Reflux; | Synthesis of (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones (6a-j); general procedure General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With piperidine; In ethanol; for 6h;Reflux; | General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With piperidine; In ethanol; for 6h;Reflux; | General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With piperidine In ethanol for 6h; Reflux; | Synthesis of (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones (6a-j); general procedure General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With piperidine; In ethanol; for 6h;Reflux; | General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With piperidine; In ethanol; for 6h;Reflux; | General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With piperidine; In ethanol; for 6h;Reflux; | General procedure: A mixture of 2a-j (1.50 mmol) and 5 (1.50 mmol) in ethanol (10 mL) was treated with a catalytic amount of piperidine. The reaction mixture was stirred under reflux until complete consumption of the substituted indolin-2-ones was observed by TLC. After cooling, the precipitate was filtered, recrystallised from absolute ethanol and dried in air to furnish pure (E)-3-(benzothiazol-2-ylmethylene)indolin-2-ones 6a-j. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With hydrogenchloride In N,N-dimethyl-formamide at 50℃; for 10h; | 1.2 Step 2 the 2-benzothiazole dimethyl acetal was added to the organic solvent DMF, according to 2-benzothiazole dimethyl acetalAldehyde and the amount of acid catalyst material ratio of 1: 5 and then add the acid catalyst hydrochloric acid, the reaction temperature was 50 ° C for 10 hours,Concentrated under reduced pressure and recrystallized from 50 mL of isopropanol to give 11.4 g of benzothiazole-2-carbaldehyde as a white solid, yield 86%, purity 99.6% |
86% | With hydrogenchloride In water; N,N-dimethyl-formamide at 50℃; for 10h; | 1.2 Step two The above 2-benzothiazole dimethyl acetal was added to DMF as an organic solvent,Follow 2-benzothiazole dimethyl acetal andThe amount of acid catalyst material ratio of 1: 5 then add the acid catalyst hydrochloric acid,50 ° C for 10 hours under the conditions of temperature,Concentrated under reduced pressure, and recrystallized from 50 mL of isopropanol,There was obtained 11.4 g of benzothiazole-2-carbaldehyde as a white solid,Yield 86%, purity 99.6% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: benzothiazole-2-carbaldehyde; 1H-indazol-5-ylamine In acetonitrile at 0℃; for 0.0833333h; Stage #2: mercaptoacetic acid With oxovanadium(IV) sulfate In acetonitrile at 0℃; for 1h; Sonication; | General Procedure for the synthesis of 2,3-diaryl-thiazolidin-4-ones (6 a-j ) and 9 (a - y) General procedure: A mixture of aromatic amine (1 equiv) and aryl aldehyde (1 equiv) in acetonitrile was stirred at 0 °C for 5 min, and then thioglycolic acid (1 equiv) was added. After 5 min, VOSO4 (5 mol%) was added to the reaction mixture at 0 °C and was sonicated for 1 h. After completion of the reaction (monitored by TLC), VOSO4 was separated by filtration and the filtrate was concentrated to dryness under reduced pressure. The residue was taken up in ethyl acetate and washed with NaHCO3 solution. Finally, the organic layer was dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure to get a crude product that was purified by column chromatography on silica gel using n-hexane/ethyl acetate solvent system as eluent in 63-86 % yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.3% | With potassium permanganate; manganese(II) acetate; In acetic acid; at 7℃; for 60h; | With 100mL glacial acetic acid as a solvent,In the manganese acetate and potassium permanganate (manganese acetate and potassium permanganate weightThe ratio of 0.1: 100)As a catalyst for catalysis,The above benzothiazole-2-carbaldehyde andThe oxygen introduced through the oxidation reaction (the weight of the catalyst accounted for benzothiazole-2-carbaldehyde 1%),Reaction temperature is 7 ,Reaction time is 60 hours,Concentration under reduced pressure, filtration, recrystallization from isopropanol,To a white solid benzothiazole 2-carboxylic acid 10.1g,Yield 80.3%, purity of 98.7% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With ammonium peroxydisulfate; caesium carbonate In dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; Irradiation; Green chemistry; regioselective reaction; | Procedure A for compounds (3a-3p) in Schemes 2 General procedure: Heterocycle (0.10mmol,1equiv)ammonium persulfate (0.30 mmol, 3 equiv), Cs2CO3(0.20mmol,2 equiv)were placed in a dry glass tube.Then, anhydrous DMSO1 mL) and2,2-diethoxyacetic acid (0.7mmol7equiv), wereinjected into the tube by syringe under a N2atmosphere.The solution was then stirred at roomtemperature under the irradiation of 15W blueLEDs strip for 24h.After completion of the reaction,the mixture was quenched by addition of1.2mL of 3.0 M HCl, stirred for 20hthen saturated Na2CO3solution was added to adjust pH tobasicextract with CH2Cl2,the combined organic layers was washed with brine, then dry overanhydrous Na2SO4. The desired products were obtained in thecorresponding yields afterpurification by flashchromatography on silica gel eluting with petroleum and ethylacetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | Stage #1: benzothiazole-2-carbaldehyde; 2,6-difluoro-3-aminobenzamide With toluene-4-sulfonic acid In methanol at 0℃; for 2h; Stage #2: With sodium cyanoborohydride In methanol for 12h; | 4.1.2. 2,6-Difluoro-3-((3-(n-butyloxy)benzyl)amino)benzamide(11) General procedure: To a well stirred mixture of 2,6-difluoro-3-aminobenzamide(10) (0.17 g, 1.0 mmol) and 3-n-butoxybenzaldehyde (0.17 g,1.0 mmol) in MeOH (10 mL) at 0 °C, was added p-toluenesulfonicacid monohydrate (0.02 g, 0.11 mmol) and the reaction mixturewasstirred for 2 h. After that, excess sodium cyanoborohydride (0.63 g,10.0 mmol)was added in portions to the reaction mixture. After theaddition, the reaction mixture was stirred for further 12 h. The reactionwas quenched by pouring into a separating funnel containing50 mL water and extracted with ethyl acetate (20 mL x 3). Thecombined organic layers were dried over MgSO4, filtered andevaporated under reduced pressure to a crude product, which wassubjected to purification by flash column chromatography on silicagel with gradient elution (20%e50% ethyl acetate in hexane) toafford the titled compound (0.15 g) in 45% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: Thiazole-2-carbaldehyde; benzothiazole-2-carbaldehyde; 1-amino-4-[(tert-butyloxycarbonyl)amino]butane In dichloromethane for 0.166667h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; Inert atmosphere; | General Procedure for the synthesis 1(a-c): General procedure: To a stirred solution of tert-butyl (4-aminobutyl)carbamate (1.88g, 10mmol) in DCM (100 mL) was added aldehyde (22 mmol) After the mixture was stirred for 10 min, NaBH(OAc)3 (22 mmol) was added and the mixture was stirred overnight at room temperature under N2. The mixture was diluted with DCM (100 mL) and washed with saturated sodium bicarbonate (100 mL), water (2 × 100 mL), and brine (100 mL). The organic layer was dried over sodium sulfate and concentrated to afford the crude product. The crude material was purified by combiflash using EtOAc in Hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Stage #1: benzothiazole-2-carbaldehyde; 1-amino-4-[(tert-butyloxycarbonyl)amino]butane In dichloromethane for 0.166667h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; Inert atmosphere; | General Procedure for the synthesis 1(a-c): General procedure: To a stirred solution of tert-butyl (4-aminobutyl)carbamate (1.88g, 10mmol) in DCM (100 mL) was added aldehyde (22 mmol) After the mixture was stirred for 10 min, NaBH(OAc)3 (22 mmol) was added and the mixture was stirred overnight at room temperature under N2. The mixture was diluted with DCM (100 mL) and washed with saturated sodium bicarbonate (100 mL), water (2 × 100 mL), and brine (100 mL). The organic layer was dried over sodium sulfate and concentrated to afford the crude product. The crude material was purified by combiflash using EtOAc in Hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In ethanol; water at 80℃; for 4h; | 4.1.1. General Procedure for the Automated Synthesis of Compounds 1-5 General procedure: Aldehyde (1.00 mmol), hydrazide (1.00 mmol), ethanol (4.0 mL) and 50 L of aqueous 1M HClwere added in a 13 mL double jacket reactor from Chemspeed equipped with condenser. The mixturewas shaken at 700 rpm for 4 h at 80 °C, then cooled down to 20 °C. The precipitate was filtrated andsuccessively washed with 2 mL of ethanol and 2 mL of ethyl ether to obtain the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.1% | Stage #1: benzothiazole-2-carbaldehyde; 2-amino-3-(3H-imidazol-4-yl)propanoic acid hydrochloride With sodium sulfate In ethanol at 20℃; for 2h; Stage #2: With ethanol; sodium tris(acetoxy)borohydride at 20℃; for 8h; | 9.3 Step 3 Preparation of Intermediate 13 Intermediate 12 (2.5 g, 15.3 mmol) and histidine hydrochloride 2.51 g (15.3 mmol) were dissolved in absolute ethanol, then anhydrous sodium sulfate (3.65 g, 30.64 mmol) was added and stirred at room temperature 2 After the reaction was carried out, sodium triacetoxyborohydride (3.90 g, 18.38 mmol) was added to the reaction system. The reaction was allowed to stand at room temperature for 8 h, and the reaction was completed by TLC. The organic layer was dried over Na 2 SO 4 overnight. The desiccant was filtered off and concentrated under reduced pressure to give 2.96 g.The yield was 67.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With hydrogenchloride In ethanol; water Reflux; | 1.1-1.2; 2.1-2.2; 3.1-3.2 Example 3 The preparation method of benzothiazole double Schiff base ratio fluorescent molecular probe for iron ion detection is as follows: 1) According to the molar ratio of benzothiazole-2-carbaldehyde to 2-hydroxy-1-naphthylhydrazine is 1: (1 to 2), Add benzothiazole-2-carbaldehyde and 2-hydroxy-1-naphthylhydrazine to 20 mL of concentrated hydrochloric acid in ethanol. The reaction was refluxed for 5-7 hours. To obtain a reaction mixture; 2) The filter cake is recrystallized with acetone and water to obtain a fluorescent molecular probe BP, which is a benzothiazole double Schiff base ratio fluorescent molecular probe for iron ion detection. The yield is calculated to be 79%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: benzothiazole-2-carbaldehyde; 2-amino-phenol In 1,4-dioxane at 100℃; for 1h; Green chemistry; Stage #2: With bis(1-butyl-3-methylimidazolium) tungstate In 1,4-dioxane at 100℃; for 4h; Green chemistry; | 2.3 General procedure for synthesis of 2-arylbenzoxazoles 3 General procedure: The mixture of o-aminophenols 1 (0.6mmol, 1.2 equiv), aldehydes 2 (0.5mmol, 1 equiv) in 1,4-dioxane (5mL) was stirred at 100°C with oil bath for 1h. [BMIm]2[WO4] (0.1mmol, 53mg, 0.2 equiv) was added to reaction mixture for further 4h at 100°C in the open air. The reaction was monitored by TLC. After completion of the reaction, the resulting solution was cooled to room temperature and pour it into the water (30mL) followed by extraction with ethyl acetate (10mL×3). The combined organic phase was washed with water three times. The solvent was removed by vacuum evaporation. The pure products 3 were obtained by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With ammonium acetate; acetic acid at 80℃; | A mixture of compound 2, benzothiazole-2-carboxaldehyde (1.5equiv.), NH4OAc (10 equiv.) was stirred and catalyzed by AcOH at 80 °C for 6 h. After cooling, pH value of the mixture was adjusted to 8 with NaOH solution. The product was exacted by CH2Cl2 and dried over Na2SO4. Then, flash column chromatography with CH2Cl2/CH3OH elution was conducted to purify the crude product. 2-(4,5-bis(4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazol-2-yl)benzo[d]thiazole (IZTZ-1): Yellow solid (41% yield). 1H NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 7.93 (d, J = 8.1 Hz, 2H), 7.62 (d,J = 8.7 Hz, 2H), 7.53-7.31 (m, 4H), 6.90 (dd, J = 14.6, 8.8 Hz, 4H),3.36-3.17 (m, 8H), 2.69-2.55 (m, 8H), 2.39 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 159.24, 153.30, 150.71, 150.22, 139.92, 134.91,128.80, 128.62, 126.31, 125.18, 122.38, 121.81, 115.68, 115.43,55.01, 48.80, 48.27, 46.05. HRMS (ESI) m/z: predicted for C32H35N7S:550.2747 [M+H]+, found 550.2753 [M+H]+. Purity,>95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.2% | With diethylamine In butan-1-ol at 50℃; Sealed tube; | 1.2 (2) Mix 2,8-dimethyl-5-hydroxyquinoline and benzothiazole-2-formaldehyde in a molar ratio of 1:3 in n-butanol solution, Add 3 drops of diethylamine, With a sealed high-pressure bottle, React at 50 °C for 1-3h, A yellow solid Ia is obtained with a yield of over 96.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With acetic acid In propan-1-ol for 24h; Reflux; Molecular sieve; | 29 Example 29 1.25 g (2.55 mmol) of azo precursor II were suspended in a mixture of 8.8 ml of n-propanol and 0.6 ml acetic acid, followed by adding 0.56 g of benzothiazole-2-carboxaldehyde (5 mmol) and 3.96 g of activated molecular sieves (4A). The mixture was refluxed for 24 hours and then cooled to RT, the solids were filtered off and washed with n-propanol. The residue was suspended in THF to dissolve the product, the solids were filtered off and washed with THF. The filtrate was evaporated yielding 1.04 g (81 %) of dark crystals of formula (29) after drying (50°C / 200 mbar). (0558) 1 H-NMR (300 MHz, CDCh): d = 7.38 (d, Aryl-H, 1 H), 7.54-7.64 (m, Aryl-H, 2H), 7.71-7.81 (m, Aryl-H, 2H), 7.85 (d, Aryl-H, 2H), 8.02-8.1 1 (m, Aryl-H, 4H), 8.17-8.27 (m, Aryl-H, 5H), 8.54 (d, Aryl-H, 1 H), 9.00 (s, CH=N, 1 H), 9.08 (d, Aryl-H, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3. 4.3.1. N-(2-(benzo[d]thiazol-2-yl)-2-oxo-1-phenylethyl)-4- methylbenzenesulfonamide (3a) White solid, 83% yield, 35 mg; m.p. 177e179 C; 1 H NMR (400 MHz, DMSO-d6) d 9.15 (d, J 9.3 Hz, 1H), 8.31e8.22 (m, 2H), 7.71e7.59 (m, 4H), 7.40e7.37 (m, 2H), 7.30e7.21 (m, 3H), 7.17 (d, J 8.1 Hz, 2H), 6.45 (d, J 9.3 Hz, 1H), 2.25 (s, 3H). 13C NMR (100 MHz, DMSO-d6) d 190.4, 164.1, 153.1, 143.2, 138.3, 137.0, 134.9, 129.8, 129.3, 129.0, 128.9, 128.7, 128.2, 127.0, 126.0, 123.7, 61.1, 21.3. HRMS (ESI, m/z) calcd. for C22H17N2O3S2Na: 445.0651, found: 445.0648 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With 2-pentafluorophenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; potassium phosphate In tetrahydrofuran at 0℃; for 12h; Molecular sieve; | General procedure for the preparation of products (3) General procedure: To a 4 mL vial equipped with a magnetic stir bar was added NHC pre-catalyst C (0.02 mmol, 20 mol%, 7.3 mg), K3PO4 (0.02 mmol, 20 mol%, 4.2 mg), 4 Å MS (100.0 mg), substrates 1 (0.10 mmol) and substrates 2 (0.15 mmol), anhydrous THF (2.0 mL). The reaction mixture was allowed to stir for 12 h at 0 C. After completion of the reaction, monitored by TLC, the mixture was concentrated under reduced pressure. The resulting crude residue was purifified via column chromatography on silica gel (v/v/v: petroleum ether/ CH2Cl2/EtOAc, from 10/2/1 to 10/2/2) to afford the desired product 3.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: benzothiazole-2-carboxaldehyde; but-2-ynoic acid; 4-tert-Butylaniline In methanol at 20℃; for 0.5h; Stage #2: Cyclohexyl isocyanide In methanol at 20℃; | General Procedures A, B and C for 4-Component Ugi Reaction General procedure: In a 6-dram vial equipped with a stir bar aldehyde (1.0 mmol, 1.0eq.), aniline (1.0 mmol, 1.0 eq.) and carboxylic acid (1.0 mmol, 1.0eq.) were combined in MeOH (4 mL). The obtained reaction mixturewas stirred for 30 min at room temperature. Afterwards cyclohexylisocyanide (0.9 mmol, 0.9 eq.) was added to the reaction mixtureand the walls of the vial were washed with 1 mL of MeOH. Thereaction mixture was continued to stir at room temperature overnight.The crude reaction mixture was evaporated in vacuo. Purificationprocedure A) The crude product was triturated withhexanes (5 mL) and filtered. The obtained product was furtherwashed with hexanes (3 x 3 mL). Purification procedure B) Thecrude product recrystallized fromCHCl3/hexanes mixture, filtereand the obtained product was further washed with hexanes (3 x3 mL). Purification procedure C) The crude product was redissolvedin DCM. The obtained crude solutionwas deposited on silica. It wasthen purified using flash column chromatography using DCM/MeOH (gradient 05%) as eluent. |
91% | Stage #1: benzothiazole-2-carboxaldehyde; but-2-ynoic acid; 4-tert-Butylaniline In methanol at 20℃; for 0.5h; Stage #2: Cyclohexyl isocyanide In methanol at 20℃; | General Procedures A, B and C for 4-Component Ugi Reaction General procedure: In a 6-dram vial equipped with a stir bar aldehyde (1.0 mmol, 1.0eq.), aniline (1.0 mmol, 1.0 eq.) and carboxylic acid (1.0 mmol, 1.0eq.) were combined in MeOH (4 mL). The obtained reaction mixturewas stirred for 30 min at room temperature. Afterwards cyclohexylisocyanide (0.9 mmol, 0.9 eq.) was added to the reaction mixtureand the walls of the vial were washed with 1 mL of MeOH. Thereaction mixture was continued to stir at room temperature overnight.The crude reaction mixture was evaporated in vacuo. Purificationprocedure A) The crude product was triturated withhexanes (5 mL) and filtered. The obtained product was furtherwashed with hexanes (3 x 3 mL). Purification procedure B) Thecrude product recrystallized fromCHCl3/hexanes mixture, filtereand the obtained product was further washed with hexanes (3 x3 mL). Purification procedure C) The crude product was redissolvedin DCM. The obtained crude solutionwas deposited on silica. It wasthen purified using flash column chromatography using DCM/MeOH (gradient 05%) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In methanol at 20℃; for 15h; Molecular sieve; Inert atmosphere; | 3.1. General Method for Synthesis of (S,E)-11-[2-(Arylmethylene)hydrazono]-pyrrolo [2,1-c] [1,4]Benzodiazepines (4a-4q) General procedure: To a solution of 3 (230 mg, 1.0 mmol) in anhydrous methanol (10 mL) was addedaldehyde (1.0 mmol). 3 Å molecular sieves (0.5 g) was also added and stirred at roomtemperature. Various modifications were used to obtain compounds 4a-4q.(Spectroscopicdata for PBD analogs (4a-4q) and typical MRM chromatograms of 4k in plasma and tissuesare available in Supplementary Materials) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With ammonium hydroxide; potassium hydroxide In ethanol at 20℃; | 2-([2,2′:6′,2″-Terpyridin]-4′-yl)-1,3-benzothiazole(TP1) General procedure: A solution of 1,3-benzothiazole-2-carbaldehyde(0.5 mmol, 81.5 mg) in 2 mL of ethanol wasadded to a solution of 2-acetylpyridine (1 mmol,121 mg) in 3 mL of ethanol. The mixture was stirred atroom temperature for 15 min, a small piece of KOHpellet (~0.05 mg) was added, 25% aqueous ammonia(1.5 mL) was then added, and the resultant mixture wasstirred at room temperature for 6 h. After completion ofthe reaction (TLC), the solid product was filtered offunder vacuum onto a sintered funnel, washed with icecoldethanol until colorless washings, and recrystallizedfrom chloroform. Yield 180 mg (98%), greenish white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With ammonium hydroxide; potassium hydroxide In ethanol at 20℃; | 2-([2,2′:6′,2″-Terpyridin]-4′-yl)-1,3-benzothiazole(TP1) General procedure: A solution of 1,3-benzothiazole-2-carbaldehyde(0.5 mmol, 81.5 mg) in 2 mL of ethanol wasadded to a solution of 2-acetylpyridine (1 mmol,121 mg) in 3 mL of ethanol. The mixture was stirred atroom temperature for 15 min, a small piece of KOHpellet (~0.05 mg) was added, 25% aqueous ammonia(1.5 mL) was then added, and the resultant mixture wasstirred at room temperature for 6 h. After completion ofthe reaction (TLC), the solid product was filtered offunder vacuum onto a sintered funnel, washed with icecoldethanol until colorless washings, and recrystallizedfrom chloroform. Yield 180 mg (98%), greenish white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: benzothiazole-2-carboxaldehyde; 1-acetyl-2,3-dihydro-1H-indol-3-one In N,N-dimethyl-formamide at 40℃; for 0.25h; Inert atmosphere; Stage #2: With triethylamine In N,N-dimethyl-formamide for 10h; Inert atmosphere; Stage #3: boron trifluoride diethyl ether complex With triethylamine In dichloromethane at 20℃; for 0.25h; Inert atmosphere; Cooling with ice; | 11 Example 11 In a (50 mL) round-bottom flask, 1-acetylindol-3-one (500 mg, 2.8 mmol) and benzothiazole-2-carbaldehyde (457 mg, 2.8 mmol) were added, purged with nitrogen, and N,N- Dimethylformamide (10 mL) was stirred for 15 minutes, placed in a 40°C water bath, followed by addition of triethylamine (0.4 mL) and vigorous stirring for 10 hours, the reaction mixture solution was added to distilled water (500 mL).After standing for some time, the orange intermediate was obtained by filtration and low temperature vacuum drying.The intermediate was added to a 250 mL round-bottom reaction flask, argon was pumped three times, and a dichloromethane solution (50 mL) was added and stirred for 5 minutes, followed by triethylamine (2 mL) at room temperature.After 10 minutes, boron trifluoride ether (2.5 mL) was slowly added dropwise in an ice bath, and the reaction was stopped when the starting material disappeared on TLC.After vacuum concentration, the product was purified by silica gel chromatography (dichloromethane/petroleum ether=1/1) to obtain the pure product (703 mg) as a blue solid, the structural formula is (A11), and the yield was 77%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.2% | Stage #1: benzothiazole-2-carboxaldehyde; 1-acetyl-2,3-dihydro-1H-indol-3-one In N,N-dimethyl-formamide at 20℃; for 0.25h; Inert atmosphere; Stage #2: With triethylamine In N,N-dimethyl-formamide for 20h; Inert atmosphere; Stage #3: triphenylborane In toluene at 110℃; for 2h; Inert atmosphere; | 22 Example 22 In a (50 mL) round-bottom flask, 1-acetylindol-3-one (500 mg, 2.8 mmol) and benzothiazole-2-carbaldehyde (457 mg, 2.8 mmol) were added, purged with nitrogen, and N,N- Dimethylformamide (10 mL) was stirred for 15 minutes, placed in a 20°C water bath, followed by addition of triethylamine (1.1 mL) and vigorous stirring for 20 hours. The reaction mixture solution was added to distilled water (500 mL).After standing for some time, the orange intermediate was obtained by filtration and low temperature vacuum drying.The dry intermediate was added to a 100 mL two-necked round-bottom flask, triphenylboron (2.66 g, 8.4 mmol) was added under nitrogen atmosphere, and redistilled toluene solution (25 mL) was added at the same time, and stirred for 5 minutes.The reaction was then heated to 110°C for 2 hours.It was cooled to room temperature, concentrated in vacuo, and purified by silica gel chromatography (dichloromethane/petroleum ether=7/3) to obtain the target product (1.05 g), the structural formula is (B11), and the yield was 85.2%. |
Tags: 6639-57-2 synthesis path| 6639-57-2 SDS| 6639-57-2 COA| 6639-57-2 purity| 6639-57-2 application| 6639-57-2 NMR| 6639-57-2 COA| 6639-57-2 structure
[ 19989-67-4 ]
Benzo[d]thiazole-6-carbaldehyde
Similarity: 0.75
[ 394223-38-2 ]
Benzo[d]thiazole-5-carbaldehyde
Similarity: 0.75
[ 1213833-90-9 ]
Benzo[d]thiazole-4-carbaldehyde
Similarity: 0.74
[ 74531-15-0 ]
4,5-Dimethylthiazole-2-carbaldehyde
Similarity: 0.72
[ 144876-37-9 ]
Benzo[d]thiazole-7-carbaldehyde
Similarity: 0.61
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H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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