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CAS No. : | 31930-36-6 | MDL No. : | MFCD00209584 |
Formula : | C5H7IO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | AELYFQSZXFFNGP-ARJAWSKDSA-N |
M.W : | 226.01 | Pubchem ID : | 643843 |
Synonyms : |
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.4 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 39.92 |
TPSA : | 26.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.55 cm/s |
Log Po/w (iLOGP) : | 2.14 |
Log Po/w (XLOGP3) : | 1.59 |
Log Po/w (WLOGP) : | 1.5 |
Log Po/w (MLOGP) : | 1.52 |
Log Po/w (SILICOS-IT) : | 1.45 |
Consensus Log Po/w : | 1.64 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.04 |
Solubility : | 2.04 mg/ml ; 0.00902 mol/l |
Class : | Soluble |
Log S (Ali) : | -1.75 |
Solubility : | 3.99 mg/ml ; 0.0176 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.41 |
Solubility : | 8.81 mg/ml ; 0.039 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.96 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With acetic acid; sodium iodide at 70℃; for 16h; Inert atmosphere; | 8 Ethyl cis-3-iodoacrylate A solution of ethyl propiolate (1.0 mL, 9.8 mmol) in glacial acetic acid (5 mL) was treated with sodium iodide (1.5 g, 10 mmol) and the reaction mixture was warmed up to 70 °C and stirred for 16 h. The reaction was quenched with H2O (5 mL) followed by aq. NaOH (1 N, 5 mL) and extracted with diethyl ether (3 * 5 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated under vacuum to afford the desired iodoacrylate as orange oil in a quantitative yield (2.23 g, 9.8 mmol). The product was used without any further purification. Rf 0.59 (Et2O/PE, 2.5:7.5); 1H NMR (500 MHz, CDCl3): δ 7.31 (1H, dd, J = 8.8, 1.0 Hz), 6.74 (1H, dd, J = 8.9, 1.3 Hz), 4.06 (2H, qd, J = 7.2, 1.7 Hz), 1.14 (3H, td, J = 7.2, 1.6 Hz); 13C NMR (125 MHz, CDCl3): δ 164.0, 129.6, 94.7, 60.4, 13.9; νmax (film) 1721, 1597, 1321, 1192, 1159, 1024 and 804 cm-1; HRMS (ESI) calcd for C5H7IO2 [M]+: 225.9491. Found: 225.9494. |
99% | With acetic acid; sodium iodide at 70℃; for 16h; Inert atmosphere; | |
98% | With acetic acid; sodium iodide |
97% | With acetic acid; sodium iodide at 70℃; for 12h; Inert atmosphere; | |
96% | With acetic acid; sodium iodide at 20 - 70℃; | |
95% | With sodium iodide In acetic acid at 70℃; for 12h; | |
95% | With acetic acid; lithium iodide In acetonitrile at 76℃; for 13h; Inert atmosphere; | |
95% | With sodium iodide In acetic acid at 70℃; for 16h; | General procedure C: General procedure: (for the synthesis of compounds 13, 31)To round bottom flask were added the NaI (10 g, 66.7 mmol). The solid was stirred and dried at reduced pressure. After 30 min, aceticacid (100 mL) and propiolate (65.4 mmol) were added to the solidand stirred at 70 C. After 16 h, the mixture was poured into icewater and extracted with diethyl ether (100 mL 3). All organiclayers were combined, neutralized with saturated sodium bicarbonate,dried (anhyd. Na2SO4), filtered and concentrated in vacuo toafford the product as a yellow liquid. |
93% | With acetic acid; sodium iodide at 110℃; for 3h; | |
92% | With acetic acid; sodium iodide at 70℃; for 12h; | |
91% | With acetic acid; lithium iodide at 70℃; for 15h; | |
90% | With acetic acid; lithium iodide at 20 - 70℃; | |
90% | With acetic acid; sodium iodide at 70℃; | |
88% | With acetic acid; sodium iodide at 70℃; for 12h; | |
84% | With sodium iodide In acetic acid at 70℃; for 16h; | |
84% | With acetic acid; sodium iodide at 60 - 80℃; | 1 Preparation of compound (2)(Z)-3-iodoethyl acrylate In a 500ml reaction flask, add glacial acetic acid (232g, 3.86mol), ethyl propiolate (58g, 0.591mol), sodium iodide (133g, 0.887mol), stir and warm up to 60-80, keep for 5-7 hours , Sampling TLC analysis, the raw material ethyl propiolate has been converted; concentrated under reduced pressure to recover glacial acetic acid; the residue is cooled by 15-25°C, and water (116ml) and methyl tert-butyl ether (174ml) are added to extract and wash, and the organics are separated The layer was washed with water (116ml), and the organic layer was concentrated to dryness to recover methyl tert-butyl ether to obtain yellow liquid (Z)-3-iodoethyl acrylate (112.2g, 0.496mol), yield 84%, HPLC purity 95.0 %. |
80% | With acetic acid; sodium iodide at 70℃; for 16h; Inert atmosphere; stereoselective reaction; | |
78% | Stage #1: propynoic acid ethyl ester With acetic acid; sodium iodide Stage #2: With diisobutylaluminium hydride optical yield given as %de; stereoselective reaction; | |
75% | With palladium diacetate; acetic acid; lithium iodide at 70℃; for 5h; | |
72% | With sodium iodide In acetic acid at 70℃; for 6h; Inert atmosphere; | |
68% | With trifluoroacetic acid at 25℃; for 8h; | |
67% | With acetic acid; sodium iodide Schlenk technique; | |
With acetic acid; sodium iodide | ||
With acetic acid; lithium iodide | ||
With acetic acid; lithium iodide In acetonitrile for 0.166667h; Inert atmosphere; Reflux; | ||
With acetic acid; sodium iodide at 70℃; for 13h; | ||
With acetic acid; potassium iodide at 70℃; for 4h; Schlenk technique; | Procedure for the synthesis of Enynoates (1) Step 1: A schlenk tube equipped with a stir-bar was charged with ethyl propiolate 4 (1 eq.), potassium iodide (1.3 eq.) and acetic acid. The mixture was stirred at 70 oC for 4 hrs. Then the reaction mass was quenched with ice-cold water and sodium bi-carbonate, extracted with ethyl acetate and organic layer was separated and washed with saturated brine solution, organic layer collected was then dried over sodium sulphate. The excess solvent was evaporated under reduced pressure on rotary evaporator to give the desired compound as the reddish oil which was used without any further purification. | |
With acetic acid; lithium iodide In acetonitrile for 12h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With diisobutylaluminium hydride In dichloromethane; toluene at -90 - -20℃; Inert atmosphere; | |
90% | With diisobutylaluminium hydride In diethyl ether; hexane at -78 - 23℃; for 2h; Inert atmosphere; | 3 (Z)-3-Iodoprop-2-en-l-ol (25): To a stirred solution of ethyl ester 24 (20.0 g, 88.0 mmol, 1.00 equiv) in Et20 (440 mL) cooled to -78 °C, was added a solution of DIBAL-H (195 mL, 1 M in hexanes, 195 mmol, 2.20 equiv) dropwise and the reaction mixture was stirred at -78 °C for 1 h and was then allowed to warm to 23 °C over 1 h. The reaction was quenched following the Fieser method: the mixture was cooled to 0 °C and water (7.80 mL) was added dropwise, after which the ice bath was removed and a 15% aqueous solution of NaOH (7.80 mL) was added dropwise followed by water (19.8 mL). The resulting mixture was stirred for 30 min and then filtered through a Celite pad. The filtrate was concentrated under reduced pressure and the crude residue was purified by distillation under reduced pressure (73-75°C head temperature, 1 Torr) to yield hydroxy iodide 25 (14.7 g, 79.2 mmol, 90% yield) as a pale yellow oil. Spectral data were identical to those found in the literature (Beruben et al, 1995). 25: NMR (600 MHz, CDCL) δ 3.93 (ddd, 7= 12.0, 5.1, 1.1 Hz, 1 H), 3.49 (dd, 7= 11.9, 8.8 Hz, 1 H), 2.61 (td, 7=7.5, 4.9 Hz, 1 H), 1.77 (br s, l H), 1.33 (ddd, 7=9.0, 7.8, 6.4 Hz, 1 H), 0.98-0.91 (m, 1 H), 0.67 (dt, 7=7.0, 5.8Hz, 1 H) ppm;13C NMR (151 MHz, CDC13) δ 202.58, 24.34, 16.60, -17.01 ppm. |
87% | With diisobutylaluminium hydride In hexane; dichloromethane at -78℃; for 1h; |
68% | With diisobutylaluminium hydride In tetrahydrofuran at -78 - 0℃; | |
8.28 g | With diisobutylaluminium hydride In diethyl ether; toluene at 0℃; for 0.5h; Inert atmosphere; | |
With lithium aluminium tetrahydride In diethyl ether at 0℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With diisobutylaluminium hydride In dichloromethane at -78℃; for 0.25h; Inert atmosphere; | |
88% | Stage #1: ethyl (Z)-3-iodopropenoate With diisobutylaluminium hydride In hexane; dichloromethane at -78℃; for 0.5h; Stage #2: With methanol; rochelle salt In diethyl ether; hexane; dichloromethane; water at -80 - 20℃; for 0.333333h; | |
With diisobutylaluminium hydride In dichloromethane; toluene at -78℃; for 0.5h; |
With diisobutylaluminium hydride In dichloromethane at -78℃; for 1h; | ||
With diisobutylaluminium hydride | ||
With diisobutylaluminium hydride In hexane; dichloromethane at -78℃; for 0.0833333h; | ||
With diisobutylaluminum hydride In n-heptane; dichloromethane at -78℃; for 0.5h; | ||
With diisobutylaluminium hydride In dichloromethane at -78℃; | ||
With diisobutylaluminium hydride In n-heptane; dichloromethane at -78℃; for 0.5h; Inert atmosphere; | ||
Stage #1: ethyl (Z)-3-iodopropenoate With diisobutylaluminium hydride In dichloromethane at -78℃; for 0.25h; Inert atmosphere; Stage #2: With methanol; water; Rochelle's salt In dichloromethane at -78 - 20℃; | ||
Stage #1: ethyl (Z)-3-iodopropenoate With diisobutylaluminium hydride In dichloromethane at -78℃; for 0.5h; Stage #2: With water; Rochelle's salt In methanol; dichloromethane at -78 - 20℃; | ||
With diisobutylaluminium hydride In dichloromethane at -80 - -75℃; Inert atmosphere; | ||
With diisobutylaluminium hydride In dichloromethane at -78℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate In toluene at 110℃; for 8h; | |
99% | With potassium carbonate In toluene at 110℃; for 8h; | 2.a Ethyl (Z)-5-phenyl-2-buten-4-ynoate (Table 2, entry 1): The general procedure was used to convert phenylacetylene and (Z)-ethyl-3-iodoacrylate to the title product. Purification by flash chromatography (15% ethyl acetate in hexanes as the eluent) gave the analytically pure product as a light yellow oil (396 mg, 99% yield). 1H NMR (400 MHz, CDCl3) δ 7.54-7.52 (m, 2H), 7.34 (m, 3H), 6.36 (d, J=11.43, 1H), 6.12 (d, J=11.42, 1H), 4.26 (q, 2H), 1.33 (t, 3H). 13C NMR (100 MHz, CDCl3) δ 164.72, 131.96, 129.10, 128.30, 128.17, 122.75, 122.57, 101.10, 86.30, 60.36, 14.23. Anal. Calc'd. for C13H12O2: C, 77.98; H, 6.04; Found C, 77.78; H, 6.06. |
93% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 3h; |
90% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 0 - 20℃; for 6h; Inert atmosphere; | |
83% | With copper(l) iodide; N,N-dimethylglycine hydrochoride; caesium carbonate In 1,4-dioxane at 80℃; for 12h; | |
63% | With copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine In acetonitrile at 50℃; for 18h; Inert atmosphere; Schlenk technique; | |
With copper(l) iodide; triethylamine In acetonitrile at 25℃; for 6h; | ||
76 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
16 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
53 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
36 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
2 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
4 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
51 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
69 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
34 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
74 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
21 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
7 %Chromat. | With caesium carbonate In toluene at 110℃; for 24h; | Using these two bi-dentate complexes as potential catalysts, a variety of bases were screened for the cross-coupling of phenylacetylene and (Z)-ethyl-3-iodoacrylate in toluene at 110° C. for 24 hours. It was found that an effective base for use with [Cu(phen)(PPh3)2]NO3 is Cs2CO3, as it afforded the desired product with a yield of 76% by GC. However, with [Cu(bipy)PPh3Br] as the catalyst and K2CO3 as the base, the yield was improved to 99%. Monitored over a period of time, it was discovered that the reaction was complete within 8 hours. Lowering the amount of base to 1.5 equivalents resulted in lower yields. Other bases such as K3PO4, Na2CO3, KOtBu, NaOtBu, Et3N and DBU were less effective with this particular reaction. When this particular reaction was run either in the absence of catalyst or in the absence of base the product was not observed by GC. Based on such results and control experiments, 10 mol % of [Cu(bipy)PPh3Br] as the catalyst, 2.0 equivalents of K2CO3 as the base in toluene, at 110° C., was used as part of a protocol for synthesizing 1,3-enynes. |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 55℃; for 6h; Inert atmosphere; Sealed tube; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In triethylamine at 50℃; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine Inert atmosphere; Schlenk technique; | Procedure for the synthesis of Enynoates (1) General procedure: Step 2: In a schlenk tube with a stir-bar, compound 5 was dissolved in triethylamine and to the stirred solution, terminal alkyne 6 and Copper iodide were added. The reaction tube was purged with argon. Then after 5-10 min. bis(triphenylphosphine)palladium(II)dichloride was added to the reaction mixture followed by argon purging. The mixture was stirred at 50oC for 2 hrs. Then the reaction mass was quenched with ice-cold water and sodium bi-carbonate, extracted with ethyl acetate and organic layer was separated and washed with saturated brine solution, organic layer collected was then dried over sodium sulphate. The reaction mixture was then filtered and concentrated under reduced pressure to give the desired compound which was then purified using5% ethyl acetate: petroleum ether as the eluent to afford the pure compound 1 as a pale yellow oil. | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 15h; | |
86% | With copper(l) iodide; triethylamine; triphenylphosphine In tetrahydrofuran at 20℃; | |
84% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; |
76% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine In tetrahydrofuran at 20℃; | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tetrabutyl ammonium fluoride In tetrahydrofuran at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With potassium carbonate In toluene at 110℃; for 8h; | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With caesium carbonate In toluene at 110℃; for 12h; | |
51% | With caesium carbonate In toluene at 110℃; for 12h; | |
51% | With caesium carbonate In toluene at 110℃; for 8h; | 2.o 5-Pyridin-3-yl-pent-2-en-4-ynoic acid ethyl ester (Table 2, entry 15): The modified procedure was used to convert 3-Ethynyl-pyridine and (Z)-ethyl-3-iodoacrylate to the title product in 12 hours. Purification by flash chromatography (30% ethyl acetate in hexane as the eluent) gave the analytically pure product as a light yellow oil (200 mg, 51% yield). 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 8.57-8.55 (dd, J=4.9, 1.5, 1H), 7.82-7.79 (td, J=7.8, 1.8, 1H), 7.29-7.26 (m, 1H), 6.38-6.35 (d, J=11.4, 1H), 6.21-6.18 (d, J=11.4, 1H), 4.29-4.23 (q, J=7.1, 2H), 1.34-1.31 (t, J=7.1, 3H). 13C NMR (100 MHz, CDCl3) δ 164.32, 152.25, 149.13, 138.58, 129.22, 122.86, 121.80, 119.68, 96.97, 89.03, 60.34, 14.08. Anal. Calcd. for C12H11NO2: C, 71.63; H, 5.51; N, 6.96; Found C, 71.77; H, 5.64; N, 6.73. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium carbonate In toluene at 110℃; for 20h; | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate In toluene at 110℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate In toluene at 110℃; for 8h; | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In triethylamine at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In toluene at 110℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate In toluene at 110℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate In toluene at 110℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In toluene at 110℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium carbonate In toluene at 110℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In toluene at 110℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate In toluene at 110℃; for 8h; | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate In toluene at 110℃; for 8h; | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate In toluene at 110℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In toluene at 110℃; for 8h; | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 55℃; for 6h; Inert atmosphere; Sealed tube; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine Inert atmosphere; Schlenk technique; | Procedure for the synthesis of Enynoates (1) General procedure: Step 2: In a schlenk tube with a stir-bar, compound 5 was dissolved in triethylamine and to the stirred solution, terminal alkyne 6 and Copper iodide were added. The reaction tube was purged with argon. Then after 5-10 min. bis(triphenylphosphine)palladium(II)dichloride was added to the reaction mixture followed by argon purging. The mixture was stirred at 50oC for 2 hrs. Then the reaction mass was quenched with ice-cold water and sodium bi-carbonate, extracted with ethyl acetate and organic layer was separated and washed with saturated brine solution, organic layer collected was then dried over sodium sulphate. The reaction mixture was then filtered and concentrated under reduced pressure to give the desired compound which was then purified using5% ethyl acetate: petroleum ether as the eluent to afford the pure compound 1 as a pale yellow oil. | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium phosphate; (1,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate In toluene at 110℃; for 4h; | |
88% | With pyridine; zinc In acetonitrile at 80℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogen iodide In toluene at 80℃; for 8h; Inert atmosphere; | |
87% | With hydrogen iodide In water; toluene at 80℃; for 8h; | |
77% | With hydrogen iodide In water; benzene at 80℃; |
With hydrogen iodide In benzene at 80℃; for 8h; | ||
14 g | With hydrogen iodide In water; toluene at 80℃; for 14h; | |
With hydrogen iodide In toluene at 80℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 4h; | |
63% | With copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 4h; | 1 6-[2-(4-Methyl-oxazole-5-carbonyl)-phenyl]-hept-2-en-4-ynoic acid ethyl ester (11c) 6-[2-(4-Methyl-oxazole-5-carbonyl)-phenyl]-hept-2-en-4-ynoic acid ethyl ester (11c) A solution of 300 mg (1.25 mmol, 1.0 eq) of alkyne 11b in 3.0 mL of dry THF was stirred in a 10 mL round bottom flask at room temperature under argon. To this solution was added 650 μL (3.75 mmol, 5.0 eq) of N,N-diisopropylethylamine followed by 340 mg (1.50 mmol, 1.2 eq) of 3-Iodo-acrylic acid ethyl ester. This solution was then sparged with argon for 10 minutes, at which point 44 mg (0.063 mmol, 0.05 eq) of PdCl2(PPh3)2 and 12 mg (0.063 mmol, 0.05 eq) of CuI were added at once and the solution was stirred at room temperature until the reaction was complete by TLC (3:1 hexane:acetone, Rf=0.30). Upon completion (~4 hours) the reaction was diluted with EtOAc and washed with 1.0 M HCl. The aqueous layer was then extracted twice with EtOAc. The combined organic fractions were then washed with saturated NaHCO3 and brine and then dried over MgSO4. Purification via silica gel flash chromatography (hexane/EtOAc) yielded 252 mg (63%) of 11c as a pale brown oil, Rf 0.47 (1:1 hexane:EtOAc). 1H-NMR (500 MHz, CDCl3): 7.92 (1H, s), 7.87 (1H, d, J=7.9 Hz), 7.56 (1H, dt, J=7.8 Hz, 1.2 Hz), 7.41 (1H, d, J=7.6 Hz), 7.35 (1H, t, J=7.6 Hz), 6.11 (1H, dd, J=11.5 Hz, 2.4 Hz), 6.04 (1H, d, J=11.5 Hz), 4.35 (1H, dq, J=7.1 Hz, 2.2 Hz), 4.21 (2H, q, J=7.1 Hz), 2.39 (3H, s), 1.57 (3H, d, J=7.1 Hz), 1.27 (3H, t, J=7.1 Hz). 13C-NMR (500 MHz, CDCl3): 185.43, 164.92, 152.18, 147.04, 145.37, 142.09, 136.11, 131.86, 129.00, 128.44, 128.35, 126.69, 123.28, 105.40, 79.35, 60.52, 29.88, 24.64, 14.42, 14.18. IR (cm-1): 2976 (m), 2213 (w), 1719 (s), 1653 (s), 1603 (m), 1579 (s), 1384 (m), 1355 (m), 1291 (m), 1183 (vs), 905 (s). HRMS (EI) calcd. for C20H19NO4: 337.1314; found: 337.1322. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: <i>tert</i>-butyl-dimethyl-(1-phenethyl-but-3-enyloxy)-silane; 2-(3-methoxyprop-1-yn-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane With cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate In acetone at 20℃; Stage #2: With rhenium(VII) oxide In diethyl ether at 20℃; for 2h; Stage #3: ethyl (Z)-3-iodopropenoate With tetrakis(triphenylphosphine) palladium(0); thallium (I) ethoxide In tetrahydrofuran; water for 1h; Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); <i>tert</i>-butylamine In benzene at 20℃; for 1h; | |
81% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
64% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With tetrabutylammomium bromide; triethylamine In acetone at 35℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tetrabutylammomium bromide; triethylamine In acetone at 35℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tetrakis(triphenylphosphine) palladium(0); triethylamine; silver carbonate In toluene at 20℃; for 4h; Schlenk technique; Inert atmosphere; | |
86% | With tetrabutylammomium bromide; triethylamine In acetone at 35℃; for 2h; | |
64% | With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; triethylamine In acetone at 35℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tetrabutylammomium bromide; triethylamine In acetone at 35℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With tetrabutylammomium bromide; triethylamine In acetone at 35℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Stage #1: 5-<<(1,1-Dimethylethyl)dimethylsilyl>oxy>-1-pentyn-3-ol With methyllithium In tetrahydrofuran at -78 - 23℃; Stage #2: With Schwartz's reagent; zinc(II) chloride In tetrahydrofuran at 23℃; for 2h; Stage #3: ethyl (Z)-3-iodopropenoate In tetrahydrofuran; acetonitrile Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium phosphate In water at 50℃; for 10h; | |
99 %Chromat. | With sodium carbonate In water; ethyl acetate; isopropyl alcohol at 50℃; for 0.00138889h; Microchannel flow reactor; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium phosphate; copper(l) iodide; cis-1,2-cyclohexane In N,N-dimethyl-formamide at 40 - 50℃; stereospecific reaction; | |
98% | With potassium phosphate; copper(l) iodide; cis-1,2-cyclohexane In N,N-dimethyl-formamide at 40 - 50℃; for 2h; Inert atmosphere; | |
With potassium phosphate; copper(l) iodide; cis-1,2-cyclohexane In N,N-dimethyl-formamide at 30 - 40℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(l) iodide; 2-(2'-pyridyl)benzimidazole; caesium carbonate In N,N-dimethyl-formamide at 40℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tetrakis(triphenylphosphine) palladium(0); silver carbonate In dimethyl sulfoxide at 70℃; for 10h; Inert atmosphere; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: C8H9NO With 9-BBN-H dimer In tetrahydrofuran at 20℃; for 5.5h; Stage #2: With caesium carbonate In tetrahydrofuran; water at 20℃; for 0.5h; Stage #3: ethyl (Z)-3-iodopropenoate With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triphenyl-arsane In tetrahydrofuran; water; N,N-dimethyl-formamide at 20℃; for 8.5h; | (Z)-α,β-Unsaturated ester 29 General procedure: To a solution of olefin 25 (27.8 mg, 0.135mmol) in THF (0.4 mL) was added a solution of 9-BBN-H dimer (49.4 mg, 0.202 mmol) in THF (1.0 mL), and the resultant solution was stirred at room temperature for 5.5 h. To the solution was added Cs2CO3 (3 M aqueous solution, 0.180 mL, 0.540 mmol), and the resultant mixture was stirred vigorously at room temperature for 30 min. To the reaction mixture were added PdCl2(dppf)·CH2Cl2 (11.0 mg, 0.0135 mmol), Ph3As (16.5 mg, 0.0540 mmol), and a solution of vinyl iodide 26 (47.3 mg, 0.209 mmol) in DMF (1.4 mL), and the resultant mixture was stirred at room temperature for 8.5 h. The reaction mixture was diluted with TBME, washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography (silica gel, 20% EtOAc/hexanes) gave (Z)-α,β-unsaturated ester 29 (31.3 mg, 76%) as a pale yellow oil: IR (film) 3348, 2952, 2360, 2341, 1715, 1521, 1249, 1196, 779, 595 cm-1;1H NMR (600 MHz, CDCl3) d7.35 (s, 1H), 6.27 (d, J = 11.5 Hz,1H), 6.08 (dt, J = 11.5, 6.4 Hz, 1H),5.95 (dt, J = 7.4, 1.4 Hz, 1H), 5.57(br s, 1H), 4.30-4.26(m, 2H), 3.71 (s, 3H), 3.65 (s, 3H), 2.79 (ddt, J = 7.3, 7.3, 1.0 Hz, 2H), 2.63 (dd, J = 7.3, 7.3 Hz, 2H) 1.87 (s, 3H); 13C NMR (150 MHz,CDCl3) d 168.3, 159.9,157.2, 141.7, 141.4, 136.1, 133.8, 127.9, 116.7, 52.1, 51.3, 39.3, 28.1, 26.0,20.6; HRMS (ESI) calcd for C15H20N2O5Na[(M + Na)+] 331.1264, found 331.1286. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: C9H11NO With 9-BBN-H dimer In tetrahydrofuran at 20℃; for 5.5h; Stage #2: With caesium carbonate In tetrahydrofuran; water at 20℃; for 0.5h; Stage #3: ethyl (Z)-3-iodopropenoate With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; triphenyl-arsane In tetrahydrofuran; water; N,N-dimethyl-formamide at 20℃; for 8.5h; | (Z)-α,β-Unsaturated ester 29 General procedure: To a solution of olefin 25 (27.8 mg, 0.135mmol) in THF (0.4 mL) was added a solution of 9-BBN-H dimer (49.4 mg, 0.202 mmol) in THF (1.0 mL), and the resultant solution was stirred at room temperature for 5.5 h. To the solution was added Cs2CO3 (3 M aqueous solution, 0.180 mL, 0.540 mmol), and the resultant mixture was stirred vigorously at room temperature for 30 min. To the reaction mixture were added PdCl2(dppf)·CH2Cl2 (11.0 mg, 0.0135 mmol), Ph3As (16.5 mg, 0.0540 mmol), and a solution of vinyl iodide 26 (47.3 mg, 0.209 mmol) in DMF (1.4 mL), and the resultant mixture was stirred at room temperature for 8.5 h. The reaction mixture was diluted with TBME, washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography (silica gel, 20% EtOAc/hexanes) gave (Z)-α,β-unsaturated ester 29 (31.3 mg, 76%) as a pale yellow oil: IR (film) 3348, 2952, 2360, 2341, 1715, 1521, 1249, 1196, 779, 595 cm-1;1H NMR (600 MHz, CDCl3) d7.35 (s, 1H), 6.27 (d, J = 11.5 Hz,1H), 6.08 (dt, J = 11.5, 6.4 Hz, 1H),5.95 (dt, J = 7.4, 1.4 Hz, 1H), 5.57(br s, 1H), 4.30-4.26(m, 2H), 3.71 (s, 3H), 3.65 (s, 3H), 2.79 (ddt, J = 7.3, 7.3, 1.0 Hz, 2H), 2.63 (dd, J = 7.3, 7.3 Hz, 2H) 1.87 (s, 3H); 13C NMR (150 MHz,CDCl3) d 168.3, 159.9,157.2, 141.7, 141.4, 136.1, 133.8, 127.9, 116.7, 52.1, 51.3, 39.3, 28.1, 26.0,20.6; HRMS (ESI) calcd for C15H20N2O5Na[(M + Na)+] 331.1264, found 331.1286. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In tetrahydrofuran; at 70℃; for 18h;Inert atmosphere; Microwave irradiation; | A suspension of 2-naphtamide 12 (50 mg, 292 mumol), cesium carbonate (95 mg, 292 mumol), CuI (3 mg, 15 mumol) and N,N'-methylenediamine (3.2 muL, 30 mumol) in degassed and dry THF (2 mL) in a 2.0-5.0 mL microwave vial, was treated dropwise with a solution of (Z)-ethyl 3-iodoacrylate (60 mg, 266 mumol) in degassed and dry THF (2 mL). The reaction mixture was stirred at 70 °C for 18 h and then allowed to cool down to rt. The light-green suspension was diluted with EtOAc (4 mL), filtered through a short pad of silica (previously deactivated with Et3N) using EtOAc (20 mL) as eluent. The filtrate was concentrated under vacuum to afford a crude green-yellow oil which was purified by flash column chromatography (silica gel, elution gradient EtOAc/PE, from 0:10 to 0.5:9.5) to afford the desired enamide 23 as a pale yellow gum in 48percent yield (34.3 mg, 128 mumol). Rf 0.16 (EtOAc/PE, 0.4:9.6); 1H NMR (500 MHz, acetone-d6): delta 11.69 (1H, bd, J = 8.8 Hz), 8.59 (1H, s), 8.20 (1H, d, J = 7.9 Hz), 8.17 (1H, d, J = 8.9 Hz), 8.09 (1H, d, J = 7.6 Hz), 8.03 (1H, dd, J = 8.5, 1.9 Hz), 7.86 (1H, dd, J = 11.1, 8.9 Hz), 7.72 (2H, dqn, J = 7.0 1.6 Hz), 5.38 (1H, d, J = 8.9 Hz), 4.31 (2H, q, J = 7.1 Hz), 1.36 (3H, t, J = 7.1 Hz); 13C NMR (125 MHz, acetone-d6): delta 170.9, 165.5, 140.5, 140.3, 137.1, 134.4, 131.4, 130.9, 130.7, 130.2, 129.5, 128.9, 125.0, 98.5, 61.7, 15.3; numax (film) 3327, 1678, 1622, 1487, 1397, 1381 and 1199 cm-1; HRMS (CI+/ISO) calcd for C16H16O3N [M+H]+: 270.1130. Found: 270.1136. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine In tetrahydrofuran at 70℃; for 18h; Inert atmosphere; Microwave irradiation; | 10 Ethyl 3-cinnamamido-Z-acrylate, 24 A suspension of cinnamamide 13 (50 mg, 340 μmol), cesium carbonate (111 mg, 340 μmol), CuI (3.1 mg, 16 μmol) and N,N'-methylenediamine (3.4 μL, 32 μmol) in degassed and dry THF (2 mL) in a 2.0-5.0 mL microwave vial, was treated dropwise with a solution of (Z)-ethyl 3-iodoacrylate (70 mg, 310 μmol) in degassed and dry THF (2 mL). The reaction mixture was stirred at 70 °C for 18 h and then allowed to cool down to rt. The light-green suspension was diluted with EtOAc (4 mL), filtered through a short pad of silica (previously deactivated with Et3N) using EtOAc (20 mL) as eluent. The filtrate was concentrated under vacuum to afford a crude green-yellow oil which was purified by flash column chromatography (silica gel, elution gradient EtOAc/PE, from 0:10 to 0.5:9.5) to afford the desired enamide 24 as a white gum in 55% yield (36 mg, 147 μmol).Rf 0.1 (EtOAc/PE, 0.4:9.6); 1H NMR (500 MHz, acetone-d6): δ 10.65 (1H, bd, J = 8.3 Hz), 7.83-7.78 (2H, m), 7.79 (1H, d, J = 16.0 Hz), 7.69 (1H, dd, J = 11.4, 9.0 Hz), 7.54-7.46 (3H, m), 7.10 (1H, d, J = 16.0 Hz), 5.24 (1H, d, J = 9.2 Hz), 4.23 (2H, q, J = 6.9 Hz), 1.31 (3H, t, J = 7.2 Hz); 13C NMR (125 MHz, acetone-d6): δ 170.2, 164.9, 145.4, 139.9, 136.4, 131.9, 130.6, 129.9, 121.7, 97.7, 61.4, 15.3; νmax (film) 3333, 2983, 1713, 1676, 1620, 1379, 1260, 1198 and 1138 cm-1; HRMS (CI+/ISO) calcd for C14H16O3N [M+H]+: 246.1130. Found: 246.1130. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In triethylamine at 50℃; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55%Spectr. | With copper(l) iodide; tetramethylammonium bromide; trans-N,N'-dimethylcyclohexane-1,2-diamine; In ethanol; at 110℃; for 72h;Inert atmosphere; Sealed tube; | General procedure: An oven dried 15 mL resealable pressure tube was charged with copper(I) iodide (19 mg, 0.1 mmol, 10 mol % unless specified otherwise), tetramethylammonium chloride (219 mg, 2.0 mmol) or tetramethylammonium bromide (616 mg, 4.0 mmol) and the iodoalkene or bromoalkene (1.0 mmol). The tube was fitted with a rubber septum, evacuated under vacuum, backfilled with argon and trans-N,N'-dimethylcyclohexane-1,2-diamine (31 muL, 0.2 mmol, 20 mol % unless specified otherwise) and ethanol (or DMSO or dioxane when specified) (2 mL) were next added. The tube was closed with a Teflon-coated screw cap and the resulting suspension was stirred and heated at 110 C in a preheated oil bath for 48 h (unless specified otherwise). When the reaction was run in ethanol or dioxane, the crude reaction mixture was cooled to rt, diluted with ethyl acetate, filtered on a plug of silica gel and concentrated. When the reaction was run in DMSO, the crude reaction mixture was cooled to rt, diluted with water (15 mL), extracted thrice with diethyl ether and the combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The crude residue was finally purified by flash column chromatography over silica gel to afford the desired chlorinated or brominated alkene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tris-(dibenzylideneacetone)dipalladium(0); silver carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran at 20 - 65℃; for 17h; Schlenk technique; Inert atmosphere; Molecular sieve; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With iron(III)-acetylacetonate In tetrahydrofuran at 0 - 25℃; for 1h; Schlenk technique; Inert atmosphere; | Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganeseReagents 1a-g with different Elecrophiles 3a-e (TP 2) General procedure: A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber septumwas charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a-e, 1.00mmol, 1.0 equiv), tetradecane as internal standard (50 μL) and freshly distilled THF (1.0 mL) as solvent.The reaction mixture was cooled to 0 °C and the bis-(aryl)manganese solution (1a-g, 0.6 equiv) wasadded dropwise whereupon a color change to dark brown could be recognized. After the addition wascomplete, the reaction mixture was stirred for a given time at room temperature and the completion ofthe cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, asaturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reducedpressure. Purification of the crude products by flash column chromatography afforded the desired crosscouplingreaction products (4a-n). Product 4l was not isolated and its yield was determined by GC and1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With iron(III)-acetylacetonate In tetrahydrofuran at 0 - 25℃; for 0.5h; Schlenk technique; Inert atmosphere; | Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganeseReagents 1a-g with different Elecrophiles 3a-e (TP 2) General procedure: A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber septumwas charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a-e, 1.00mmol, 1.0 equiv), tetradecane as internal standard (50 μL) and freshly distilled THF (1.0 mL) as solvent.The reaction mixture was cooled to 0 °C and the bis-(aryl)manganese solution (1a-g, 0.6 equiv) wasadded dropwise whereupon a color change to dark brown could be recognized. After the addition wascomplete, the reaction mixture was stirred for a given time at room temperature and the completion ofthe cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, asaturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reducedpressure. Purification of the crude products by flash column chromatography afforded the desired crosscouplingreaction products (4a-n). Product 4l was not isolated and its yield was determined by GC and1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With iron(III)-acetylacetonate In tetrahydrofuran at 0 - 25℃; for 1h; Schlenk technique; Inert atmosphere; | Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganeseReagents 1a-g with different Elecrophiles 3a-e (TP 2) General procedure: A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber septumwas charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a-e, 1.00mmol, 1.0 equiv), tetradecane as internal standard (50 μL) and freshly distilled THF (1.0 mL) as solvent.The reaction mixture was cooled to 0 °C and the bis-(aryl)manganese solution (1a-g, 0.6 equiv) wasadded dropwise whereupon a color change to dark brown could be recognized. After the addition wascomplete, the reaction mixture was stirred for a given time at room temperature and the completion ofthe cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, asaturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reducedpressure. Purification of the crude products by flash column chromatography afforded the desired crosscouplingreaction products (4a-n). Product 4l was not isolated and its yield was determined by GC and1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With iron(III)-acetylacetonate In tetrahydrofuran at 0 - 25℃; for 1h; Schlenk technique; Inert atmosphere; | Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganeseReagents 1a-g with different Elecrophiles 3a-e (TP 2) General procedure: A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber septumwas charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a-e, 1.00mmol, 1.0 equiv), tetradecane as internal standard (50 μL) and freshly distilled THF (1.0 mL) as solvent.The reaction mixture was cooled to 0 °C and the bis-(aryl)manganese solution (1a-g, 0.6 equiv) wasadded dropwise whereupon a color change to dark brown could be recognized. After the addition wascomplete, the reaction mixture was stirred for a given time at room temperature and the completion ofthe cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, asaturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reducedpressure. Purification of the crude products by flash column chromatography afforded the desired crosscouplingreaction products (4a-n). Product 4l was not isolated and its yield was determined by GC and1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With iron(III)-acetylacetonate In tetrahydrofuran at 0 - 25℃; for 1h; Schlenk technique; Inert atmosphere; | Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganeseReagents 1a-g with different Elecrophiles 3a-e (TP 2) General procedure: A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber septumwas charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a-e, 1.00mmol, 1.0 equiv), tetradecane as internal standard (50 μL) and freshly distilled THF (1.0 mL) as solvent.The reaction mixture was cooled to 0 °C and the bis-(aryl)manganese solution (1a-g, 0.6 equiv) wasadded dropwise whereupon a color change to dark brown could be recognized. After the addition wascomplete, the reaction mixture was stirred for a given time at room temperature and the completion ofthe cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, asaturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reducedpressure. Purification of the crude products by flash column chromatography afforded the desired crosscouplingreaction products (4a-n). Product 4l was not isolated and its yield was determined by GC and1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With iron(III)-acetylacetonate In tetrahydrofuran at 0 - 25℃; for 0.5h; Schlenk technique; Inert atmosphere; | Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganeseReagents 1a-g with different Elecrophiles 3a-e (TP 2) General procedure: A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber septumwas charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a-e, 1.00mmol, 1.0 equiv), tetradecane as internal standard (50 μL) and freshly distilled THF (1.0 mL) as solvent.The reaction mixture was cooled to 0 °C and the bis-(aryl)manganese solution (1a-g, 0.6 equiv) wasadded dropwise whereupon a color change to dark brown could be recognized. After the addition wascomplete, the reaction mixture was stirred for a given time at room temperature and the completion ofthe cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, asaturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reducedpressure. Purification of the crude products by flash column chromatography afforded the desired crosscouplingreaction products (4a-n). Product 4l was not isolated and its yield was determined by GC and1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | Stage #1: 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: ethyl (Z)-3-iodopropenoate In N,N-dimethyl-formamide at 20℃; for 3h; | General procedure D: General procedure: (for the synthesis of compounds 14a-14d,22, 32) To a solution of 3-phenyl-1H-pyrazole (32.8 mmol) in DMF(50 mL) was added DABCO (7.4 g, 65.6 mmol). The mixture wasstirred at rt for 30 min and iodoacrylate (65.6 mmol) was slowlyadded dropwise. The mixture was stirred at rt for 3 h. After TLCmonitoring, the mixture was poured into water (400 mL) andextracted with ethyl acetate (100 mL 3). All organic layers werecombined, washed (saturated sodium chloride solution,100 mL 2), dried (anhyd. Na2SO4), filtered and concentrated invacuo to afford the crude product. Purification by column chromatography(silica gel, ethyl acetate: petroleum ether 1:20)afford the product as a white solid. |
7.9 g | Stage #1: 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: ethyl (Z)-3-iodopropenoate In N,N-dimethyl-formamide at 20℃; for 3h; | 1 In a 250mL eggplant-shaped flask, add 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole 2 (8.5g, 30.2mmol), and dissolve in DMF (40mL), DABCO (8.5 g, 75.5 mmol) was added thereto. After the mixture was continuously stirred at room temperature for 30 min, ethyl (Z)-3-iodoacrylate (7.5 g, 33.2 mmol) was added dropwise to the reaction solution. The reaction was then stirred at room temperature for 3 h. After the completion of the reaction monitored by TLC, the reaction solution was poured into an ice-water mixed solution (400 mL). Extract with ethyl acetate (80 mL×3), combine the organic phases and wash with saturated sodium chloride solution (100 mL×1), dry with anhydrous Na2SO4, filter and evaporate the solvent under reduced pressure to obtain a crude compound. The obtained crude product was purified by column chromatography (PE/EtOAc=25:1) to obtain the compound (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid ethyl ester 3 (7.9g, yield 68.2%, purity 98%), white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium carbonate In ethanol at -10 - 10℃; | 2 Compound (4) Preparation of (Z)-3-(3-bromo-1H-1,2,4-triazol-1-yl) ethyl acrylate In a 500ml reaction flask, add 3-bromo-1H-1,2,4-triazole (20g, 0.135mol), ethanol (120ml), potassium carbonate (37.6g, 0.27mol), stir and cool to -10°-10° , add (Z)-3-iodoethyl acrylate (36.6g, 0.162mol) dropwise, keep for 1-2 hours after adding, sample TLC for analysis, raw material 3-bromo-1H-1,2,4-triazole The conversion is complete; the ethanol is recovered by concentration under reduced pressure; the temperature of the residue is reduced by 15-25, and water (60ml) and ethyl acetate (100ml) are added to extract and wash. The organic layer is separated and washed with water (60ml); the organic layer is concentrated under reduced pressure to dryness Ethyl acetate was recovered, and the residue was crystallized by adding methanol (40ml), filtered, washed, and dried to obtain an off-white solid powder (Z)-3-(3-bromo-1H-1,2,4-triazol-1-yl ) Ethyl acrylate (25.2g, 0.103mol), yield 76%, HPLC purity 98.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: ethyl (Z)-3-iodopropenoate With diisobutylaluminium hydride In dichloromethane at -78℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: n-hexylmagnesium bromide In dichloromethane at -70 - 20℃; Inert atmosphere; Schlenk technique; | Synthesis of (Z)-1-iodonon-1-en-3-ol 9 A dry and argon-flushed 100 mL Schlenk-flask equipped with a thermometer charged with ethyl cis-3-iodoacrylate (3.39 g, 15.0 mmol) and DCM (30 mL) was cooled to -78 °C. DIBAL-H (1.00 M in DCM, 15 mL, 15.0 mmol) was slowly added so that the temperature of the reaction mixture did not exceed -75 °C. After stirring at -78 °C for 30 min, hexylmagnesium bromide (16.5 mmol) was added dropwise at -70 °C. The reaction was allowed to warm to room temperature and stirred overnight. 1.00 M HCl (30 mL) was added dropwise at -5 °C and the mixture was warmed to room temperature. After extraction with diethyl ether (3 x 30 mL), the organic phase was dried over MgSO 4 . The solvent was evaporated and the crude product was purified via column chromatography (isohexane:ethyl acetate = 9:1, R f = 0.30) to give the product (3.48 g, 13.0 mmol, 87% yield) as a yellowish oil. 1 H-NMR (400 MHz, CDCl 3 , ppm) = 6.33 (dd, J = 7.6, 0.9 Hz, 1H), 6.24 (t, J = 7.6 Hz, 1H), 4.40 (tdd, J = 7.3, 5.9, 0.9 Hz, 1H), 1.76 - 1.60 (m, 2H), 1.61 - 1.50 (m, 1H), 1.48 - 1.17 (m, 8H), 0.96 - 0.74 (m, 3H). 13 C-NMR (101 MHz, CDCl 3 , ppm) = 143.6, 82.5, 74.6, 36.1, 31.9, 29.4, 25.1, 22.7, 14.3. IR (ATR, cm -1 ) = 2924, 2854, 1456, 1377, 1171. MS (EI, 70 eV, %) m/z = 183 (100), 81 (11). HRMS (EI, 70 eV) m/z: calc. for C 3 H 4 OI: 182.9307; found 182.9301. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 3-(3,5-bis(trifluoromethyl)phenyl)-4-methyl-1H-pyrazole With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: ethyl (Z)-3-iodopropenoate In N,N-dimethyl-formamide at 20℃; for 3h; | General procedure D: General procedure: (for the synthesis of compounds 14a-14d,22, 32) To a solution of 3-phenyl-1H-pyrazole (32.8 mmol) in DMF(50 mL) was added DABCO (7.4 g, 65.6 mmol). The mixture wasstirred at rt for 30 min and iodoacrylate (65.6 mmol) was slowlyadded dropwise. The mixture was stirred at rt for 3 h. After TLCmonitoring, the mixture was poured into water (400 mL) andextracted with ethyl acetate (100 mL 3). All organic layers werecombined, washed (saturated sodium chloride solution,100 mL 2), dried (anhyd. Na2SO4), filtered and concentrated invacuo to afford the crude product. Purification by column chromatography(silica gel, ethyl acetate: petroleum ether 1:20)afford the product as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: 3-(3,5-bis(trifluoromethyl)phenyl)-1H-pyrazole-4-carbonitrile With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: ethyl (Z)-3-iodopropenoate In N,N-dimethyl-formamide at 20℃; for 3h; | General procedure D: General procedure: (for the synthesis of compounds 14a-14d,22, 32) To a solution of 3-phenyl-1H-pyrazole (32.8 mmol) in DMF(50 mL) was added DABCO (7.4 g, 65.6 mmol). The mixture wasstirred at rt for 30 min and iodoacrylate (65.6 mmol) was slowlyadded dropwise. The mixture was stirred at rt for 3 h. After TLCmonitoring, the mixture was poured into water (400 mL) andextracted with ethyl acetate (100 mL 3). All organic layers werecombined, washed (saturated sodium chloride solution,100 mL 2), dried (anhyd. Na2SO4), filtered and concentrated invacuo to afford the crude product. Purification by column chromatography(silica gel, ethyl acetate: petroleum ether 1:20)afford the product as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: 3-(3,5-bis(trifluoromethyl)phenyl)-4-fluoro-1H-pyrazole With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: ethyl (Z)-3-iodopropenoate In N,N-dimethyl-formamide at 20℃; for 3h; | General procedure D: General procedure: (for the synthesis of compounds 14a-14d,22, 32) To a solution of 3-phenyl-1H-pyrazole (32.8 mmol) in DMF(50 mL) was added DABCO (7.4 g, 65.6 mmol). The mixture wasstirred at rt for 30 min and iodoacrylate (65.6 mmol) was slowlyadded dropwise. The mixture was stirred at rt for 3 h. After TLCmonitoring, the mixture was poured into water (400 mL) andextracted with ethyl acetate (100 mL 3). All organic layers werecombined, washed (saturated sodium chloride solution,100 mL 2), dried (anhyd. Na2SO4), filtered and concentrated invacuo to afford the crude product. Purification by column chromatography(silica gel, ethyl acetate: petroleum ether 1:20)afford the product as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | Stage #1: 3-(3,5-bis(trifluoromethyl)phenyl)-4-chloro-1H-pyrazole With 1,4-diaza-bicyclo[2.2.2]octane In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: ethyl (Z)-3-iodopropenoate In N,N-dimethyl-formamide at 20℃; for 3h; | General procedure D: General procedure: (for the synthesis of compounds 14a-14d,22, 32) To a solution of 3-phenyl-1H-pyrazole (32.8 mmol) in DMF(50 mL) was added DABCO (7.4 g, 65.6 mmol). The mixture wasstirred at rt for 30 min and iodoacrylate (65.6 mmol) was slowlyadded dropwise. The mixture was stirred at rt for 3 h. After TLCmonitoring, the mixture was poured into water (400 mL) andextracted with ethyl acetate (100 mL 3). All organic layers werecombined, washed (saturated sodium chloride solution,100 mL 2), dried (anhyd. Na2SO4), filtered and concentrated invacuo to afford the crude product. Purification by column chromatography(silica gel, ethyl acetate: petroleum ether 1:20)afford the product as a white solid. |
Tags: 31930-36-6 synthesis path| 31930-36-6 SDS| 31930-36-6 COA| 31930-36-6 purity| 31930-36-6 application| 31930-36-6 NMR| 31930-36-6 COA| 31930-36-6 structure
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P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
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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