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CAS No. : | 5389-87-7 | MDL No. : | MFCD00000983 |
Formula : | C10H17Cl | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | WLAUCMCTKPXDIY-JXMROGBWSA-N |
M.W : | 172.70 | Pubchem ID : | 6372219 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P210-P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362-P370+P378-P403+P233-P403+P235-P405-P501 | UN#: | N/A |
Hazard Statements: | H227-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 |
---|---|---|
67 %Spectr. | With 1-pyrrolidinecarboxaldehyde; sodium bromide In acetone at 0 - 20℃; for 20.5 h; | General procedure: In the presence of 2.5 molpercent FPyr allylic bromide 8 was synthesized with BzCI (1.2 equiv) according to general procedure VIII (chapter 4.9.1, t = 20 h) in 67percent yield as shown by internal standard (ratio oflinear and branched regioisomer of 98:2). Besides chloride 24 was obtained in 7percent yield (ratio bromide 84/chloride 24 91:9) together with geranyl benzoate E-34 in 12percent yield (ratio 84+24/34 86:14). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With titanium tetrachloride; N-methylaniline In dichloromethane at -23℃; for 1h; | |
97% | With chloro-trimethyl-silane; potassium carbonate In Petroleum ether at 0℃; for 2h; | |
97% | With dmap; triethylamine; p-toluenesulfonyl chloride In dichloromethane for 3h; Ambient temperature; |
94% | With Amberlite IRA 93 (PCl5 form) In hexane for 2h; Heating; | |
94% | With N-chloro-succinimide; dimethylsulfide In dichloromethane Inert atmosphere; | i Synthesis was carried out with geraniol as a starting material. The hydroxy group of geraniol was chlorinated using N-chlorosuccinimide (NCS) and dimethyl sulfide (DMS) in anhydrous dichloromethane in a nitrogen atmosphere to obtain a chloride (compound represented by (i) below) (yield: 94%). |
88% | With tetrachloromethane; triphenylphosphine Reflux; | |
87.5% | With pyridine; phosphorus trichloride In hexane at -5 - 5℃; for 0.5h; | 3.2.1. General Procedure for the Preparation of Intermediate 2 Intermediate 2 was synthesized using the published method [8]. Briefly, phosphorus trichloride (650 mmol) was added to dried anhydrous pyridine (325 mmol) and dried n-hexane (100 mL) in a 500 mL round bottom flask. After the mixture was cooled to 0 °C in ice-salt bath, geraniol (16.23 mmol)and dried n-hexane (20 mL) was dropwise added to the mixture between 0 °C and 5 °C. The mixturewas stirred for 30 min under -5 °C followed by washing with NaCl saturated solution (1 x 30 mL)and n-hexane (3 x 30 mL). The organic phase was combined and separately washed with saturated NaCl solution and saturated NaHCO3 solution until the pH = 7.0. After dried with anhydrous sodium sulfate, the organic phase was concentrated under reduced pressure to give the intermediate 2 (yellow liquid, yield 87.5%). |
86% | ||
84% | With 2,4,6-trimethyl-pyridine; methanesulfonyl chloride; lithium chloride | |
83% | Stage #1: Geraniol With methanesulfonyl chloride In pentane at -5℃; for 0.5h; Stage #2: With pyridine In pentane at 20℃; for 14h; | |
83% | With 1-pyrrolidinecarboxaldehyde; benzoyl chloride In tert-butyl methyl ether | |
80% | With N-chloro-succinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | |
80% | With N-chloro-succinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | To a solution of geraniol (1.5 g, 10 mmol) in DCM (20 mL), NCS (1.5 g, 11 mmol) and PPh3 (3.1 g, 12 mmol) were sequentially added at 0 °C. After being stirred at rt for 2 h, the solvent was removed under reduced pressure, and then residue was filtered through a pad of Celite with hexane as an eluant. The filtrate was evaporated under reduced pressure. The residue was purified by Kugelrohr disitillation to provide 5b (1.4 g, 8 mmol) in 80% yield. |
79% | With benzoyl chloride; 2,3-diethyl-2-cyclopropen-1-one In tert-butyl methyl ether at 20℃; for 24h; | |
77% | With pyridine; methanesulfonyl chloride In pentane at 25℃; for 5h; | |
74% | With N-chloro-succinimide; dimethylsulfide In dichloromethane at 0℃; for 2.5h; | |
73% | With tetrachloromethane; triphenylphosphine In dichloromethane for 6h; Ambient temperature; | |
61% | With methanesulfonyl chloride; triethylamine; lithium chloride In dichloromethane at 20℃; for 16h; | |
30% | With toluene-4-sulfonic acid; 1-butyl-3-methylimidazolium chloride In toluene at 200℃; for 0.05h; microwave irradiation; | |
With pyridine; thionyl chloride In diethyl ether | ||
With tetrachloromethane; tributylphosphine In Petroleum ether | ||
With tetrachloromethane; triphenylphosphine | ||
With tetrachloromethane; triphenylphosphine In acetonitrile at 25℃; | ||
With tetrachloromethane; triphenylphosphine for 48h; Ambient temperature; | ||
With N-chloro-succinimide; dimethylsulfide | ||
With tetrachloromethane; triphenylphosphine for 2h; Heating; | ||
With N-chloro-succinimide; dimethylsulfide In dichloromethane at -40 - 0℃; for 2h; | ||
14.1 g | With N-chloro-succinimide; dimethylsulfide In dichloromethane at 0℃; for 1h; | |
With triphenylphosphine In tetrachloromethane | ||
With tetrachloromethane; triphenylphosphine In acetonitrile at 22℃; for 19h; | ||
With n-butyllithium; p-toluenesulfonyl chloride; lithium chloride In diethyl ether at 0℃; | ||
With N-chloro-succinimide In dichloromethane at -40 - 0℃; | ||
Multi-step reaction with 2 steps 1: Et3N / tetrahydrofuran / -78 °C 2: LiCl / tetrahydrofuran / 0 °C | ||
With tetrachloromethane; triphenylphosphine for 1h; Reflux; | ||
With N,N-dimethyl-formamide; phosphorus trichloride In tetrahydrofuran for 0.5h; | ||
With pyridine; phosphorus trichloride | ||
With tetrachloromethane; triphenylphosphine at 85℃; for 3h; | General Experimental Procedure for Preparation of Allylic Chlorides: General procedure: Into a two-necked flask (300 mL), the corresponding alcohol (100 mmol) was placedand diluted with CCl4 (60 mL). To the solution, PPh3 (120 mmol) was added, and themixture was heated at 85 °C for 3 h. After the completion of reaction, the resultingwhite suspension was cooled to room temperature and then hexane (50 mL) was added.The mixture was filtered and the precipitate was washed with hexane (10 mL) threetimes. The combined organic layer was concentrated in vacuo followed by distillationunder reduced pressure affording the corresponding allylic chloride as a colorless liquid. | |
With N-chloro-succinimide; dimethylsulfide In dichloromethane at -40 - 20℃; for 2.25h; Inert atmosphere; | ||
With tetrachloromethane; triphenylphosphine | ||
With tetrachloromethane; triphenylphosphine | ||
With tetrachloromethane; triphenylphosphine Reflux; | ||
With N-chloro-succinimide; dimethylsulfide In dichloromethane | ||
With phosphorus trichloride In tetrahydrofuran; N,N-dimethyl-formamide for 0.5h; Inert atmosphere; Cooling with ice; | ||
With thionyl chloride In dichloromethane for 1h; Cooling with ice; Reflux; | 3; 5 Example 3(E)-2-(6-(((3,7-dimethyloctyl-2,6-dien-1-yl)oxy)-2,3-dihydrobenzofuran-3-yl ) Acetic acid(I) Geraniol (1 g, 6.5 mmol) was added to the pre-cooled dichloromethane solution of 5 ml of thionyl chloride in an ice bath, stirred well, and then heated to reflux for 1 h.The reaction solution was evaporated under reduced pressure to remove excess thionyl chloride, the resulting brown oil was dissolved in 20 ml of THF, and the raw material ester (1 equivalent), anhydrous potassium carbonate (3 equivalent), and the catalytic amount KI were added.Heat to 60 °C to react for 8 h, filter, and evaporate the solvent under reduced pressure. The residue is dissolved in 30 ml of water, extracted with ethyl acetate (20 ml × 3), and the organic phases are combined.Wash with saturated brine (15 ml × 2), dry with anhydrous sodium sulfate, filter,The filtrate was evaporated under reduced pressure to remove the solvent, and the residue was purified by column chromatography (petroleum ether/ethyl acetate, 5:1, v/v) to obtain a white solid, which was dissolved in 4 mL tetrahydrofuran, 6 mL methanol and 2 mL water.Add LiOH (2 equivalents), react at room temperature for 8 hours, distill off tetrahydrofuran and methanol under reduced pressure,Add 1N dilute hydrochloric acid dropwise under the ice water bath to adjust the PH 2-3, and a white solid precipitated out, filtered by suction,After drying, a white powdery solid compound I was obtained. | |
With N-chloro-succinimide; dimethylsulfide In dichloromethane at -40 - 0℃; for 2.5h; | ||
95 %Spectr. | With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In chloroform-d1 at 0 - 20℃; for 0.5h; Inert atmosphere; regioselective reaction; | 4.2. General procedure for the reaction of a-haloenamines withallylic and propargylic alcohols General procedure: Reactions were performed in an oven- or flame-dried three neckround-bottomed flask under dry argon and with magnetic stirring. The flask was equipped with a septum and a refrigerator isolated from moisture by an oil trap. A solution of alcohol in CDCl3 or CH2Cl2 was syringed in through the septum and cooled down at 0 °C. A solution of α-haloenamine (1.1 equiv.) was then syringed into the flask and the mixture was left at room temperature. The reaction was followed by 1H NMR. Yields were determined after removal of the solvent either by 1H NMR using an added standard (usually benzene or toluene) or by GLC. In some cases, the halides were purified by distillation or flash chromatography. The isolated yields were always very close to those measured by NMR or GLC. Most of the halogenation products obtained in this study were known compounds: their spectroscopic properties have been shown to be identical to those reported in the literature Therefore, no data or only 1H NMR are reported for these molecules. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; triethylamine In diethyl ether for 12h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts; | ||
With 1-pyrrolidinecarboxaldehyde; benzoyl chloride In tert-butyl methyl ether at 0 - 20℃; Sealed tube; | ||
With thionyl chloride In diethyl ether at 0 - 20℃; for 2.25h; | General procedure: According to the general procedure VII (see chapter4.4.1.3) geraniol E-14(1.00 mmol) waschlorinated with thionyl chloride. If not otherwise mentioned conversion 98% according to ‘H-N MR of the crude product. 1. Yield determined by NMR-standard (dodecane). 2. Ratio I/b-24 wasdetermined by ‘H-NMR of the crude material. 3. No aqueous work up was performed. 4. 95% conversion. 5. Detailed conditions: BzCI (1.1 equiv), FPyr (10 mol%) in MTBE (2 M), 18 h 0 °C to rt. 6. Detailed conditions: BzCI (1.01 equiv), FPyr (10 mol%) in MTBE (2 M), 17 h 0 °C to rt. 7. Isolated yield after distillation.* Comparative Example. |
1: 67 %Spectr. 2: 9 %Spectr. | With 1-pyrrolidinecarboxaldehyde; 1,3,5-trichloro-2,4,6-triazine In acetone at 20℃; for 24h; Sealed tube; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triphenylphosphine In chloroform at 25℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 46 % Chromat. 2: 54% | With tri-n-butyl-tin hydride; lithium chloride In tetrahydrofuran at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 54 % Chromat. 2: 46% | With carbon monoxide; tri-n-butyl-tin hydride; lithium chloride In tetrahydrofuran at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
61% | With n-butyllithium In hexane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With trichlorosilane; N-ethyl-N,N-diisopropylamine; copper(l) chloride In diethyl ether at 20℃; for 20h; | |
With trichlorosilane; N-ethyl-N,N-diisopropylamine; copper(l) chloride In diethyl ether for 10h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: trimethyl(prop-1-ynyl)silane With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1.5h; Inert atmosphere; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran; hexane at -78℃; for 2h; Inert atmosphere; Stage #3: With tetrabutyl ammonium fluoride In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; | |
44% | Stage #1: trimethyl(prop-1-ynyl)silane With n-butyllithium In tetrahydrofuran; hexane at -78 - -20℃; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran; hexane at -78℃; for 2h; Stage #3: With potassium carbonate In ethanol at 20℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃; for 24h; | |
With potassium carbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at -60 - 0℃; for 2.05h; regioselective reaction; | ||
With 3-chloro-benzenecarboperoxoic acid In chloroform at 0℃; for 1h; Inert atmosphere; | 4.1. (E)-4-methyldec-4-en-8-ynal (10) Geranyl chloride (5.8 g, 33.6 mmol, 1.0 equiv) was dissolved in 336 mL of chloroform. Solution was then cooled to 0°C and then mCPBA (77% purity) (7.9 g, 35.3 mmol, 1.05 equiv) was added in small portions over 30 min. After addition, solution was stirred for additional 30 min at 0°C. Solution was then extracted five times with 1M NaHCO3. Organic layer was washed with water, brine, dried over Na2SO4 and concentrated to give 6.34 g (100% yield, ca. 90-95 % pure by 1H NMR) of epoxide 20 as a colorless liquid, which was used in the next step without further purification and for which the characterization data matched literature values:32 1H NMR (400 MHz, CDCl3) δ 5.50 (td, 1H, J=7.9, 1.1), 4.10 (d, 2H. J=8.0), 2.69 (t, 1H, J=6.2), 2.29-2.11 (m, 2H), 1.74 (s, 3H), 1.66 (m, 2H), 1.30 (s, 3H), 1.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 141.7, 120.8, 63.8, 58.4, 40.8, 36.1, 26.9, 24.8, 18.7, 16.0. Propargyl bromide (2.97 g, 80 wt% in toluene, 20 mmol, 2.15 mL, 2.4 equiv) was added dropwise to a cold (-78°C) solution of BuLi (25 mL, 1.6 M in hexanes, 40 mmol, 4.8 equiv) and TMEDA (1.162 g, 10 mmol, 1.5 mL, 1.2 equiv) in 25 mL of ether. The resulting solution was stirred for 20 min at -78°C, and then a mixture of epoxide 20 (1.572 g, 8.33 mmol, 1.0 equiv) and TBAI (303 mg, 0.833 mmol, 0.1 equiv) in 5 mL of ether was then added by cannula, followed by rinsing with two additional 5-mL portions of ether. The reaction mixture was then switched to a 0°C bath and stirred for 1 h, and then the cloudy mixture was diluted with 50 mL of THF and 6.41 g (50 mmol, 6.03 mL, 6.0 equiv) of DMPU, followed by the dropwise addition of 6.30 g (50 mmol, 4.78 mL, 6.0 equiv.) of dimethyl sulfate. The 0°C bath was then removed and the reaction stirred for 1 h at rt. Reaction was then cooled to 0°C and 25 mL of 5% NH3 solution was added to quench the unreacted dimethyl sulfate. The reaction mixture was stirred for 1 h at rt, then diluted with water, and extracted three times with ethyl acetate. Organic extracts were washed twice ammonium chloride, twice with water, and once with brine, and then dried over Na2SO4, concentrated under rotary evaporator and subjected to column chromatography using 3% ethyl acetate/hexanes to afford 1.14 g (67% yield) of 17 as a colorless liquid: 1H NMR (400 MHz, CDCl3) δ 5.21 (t, 1H, J=5.6), 2.71 (t, 1H. J=6.3), 2.25-2.05 (m, 6H), 1.77 (t, 3H), 1.72-1.56 (m, 5H), 1.31 (s, 3H), 1.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 135.4, 123.6, 79.1, 75.4, 64.1, 58.4, 36.3, 27.7, 27.4, 24.9, 19.1, 18.7, 16.1, 3.5. HRMS (APCI) Calcd for C14H23O [M+H]: 207.1743, found: 207.1746. A cold (0°C) solution of 17 (540 mg, 2.62 mmol, 1.0 equiv, prepared as described above) in 10.5 mL of 1: 1 THF: H2O was then treated with sodium periodate (1.35 g, 6.28 mmol, 2.4 equiv), followed by the addition of periodic acid (59.7 mg, 0.262 mmol, 0.1 equiv). The resulting mixture was stirred for 3 h at 0°C and 1 h at rt and then partitioned between cold (0°C) 1M NaHCO3 and EtOAc. The aqueous layer was extracted with three portions of ethyl acetate. Organic layers were then combined and washed twice with water, brine and dried over sodium sulfate. Reaction mixture was then concentrated using rotary evaporator to give a quantitative recovery of crude aldehyde 10 (67% overall from geranyl chloride) as a colorless oil, which was used without purification in the next step. Characterization data for aldehyde 10 matched literature data:14 1H NMR (400 MHz, CDCl3) δ 9.80-9.74 (t, 1H, J=1.2), 5.21 (t, 1H, J=5.7), 2.52 (tq, 2H, J=8, 1.2), 2.33 (t, 2H, J=8), 2.2-2.07 (m, 4H), 1.76 (t, 3H, J=2.4), 1.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 202.6, 134.3, 124.1, 78.9, 75.6, 42.1, 31.8, 27.6, 19.0, 16.2, 3.4. Aldehyde 10 has strong irritating odor, which is felt even when the sample is in the fume hood. |
With potassium carbonate; 3-chloro-benzenecarboperoxoic acid at -60 - 0℃; for 1.16667h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In tetrahydrofuran at -20℃; | |
87% | Stage #1: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran at -20℃; Stage #2: phenylmagnesium bromide In tetrahydrofuran; diethyl ether at -20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With lithium hydroxide; 1-butyl-3-methylimidazolium Tetrafluoroborate at 35℃; for 3h; | |
34% | With lithium hydroxide In N,N-dimethyl-formamide | ii Next, the chloride was reacted with ethyl cyanoacetate in the presence of lithium hydroxide in anhydrous N,N-dimethylformamide to obtain an ester form (compound represented by (ii) below) (yield: 34%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | Stage #1: tetra(n-butoxy)silane With anilinium hypophosphorous salt In acetonitrile for 2h; Heating; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene With 1,3-bis-(diphenylphosphino)propane In acetonitrile Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: With zinc dibromide In tetrahydrofuran; hexane at -78 - 0℃; for 0.5h; Stage #3: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran; hexane; N,N-dimethyl-formamide at 70℃; for 10h; | |
74% | With copper(l) iodide; potassium carbonate; sodium sulfite In N,N-dimethyl-formamide at 30℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: tert-Butyldimethyl(prop-2-ynyloxy)silane With n-butyllithium In hexane at -78℃; for 0.5h; Stage #2: With zinc dibromide In tetrahydrofuran; hexane at -78 - 0℃; for 0.5h; Stage #3: 1-chloro-3,7-dimethylocta-2,6-diene In hexane; N,N-dimethyl-formamide at 70℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: With zinc dibromide In tetrahydrofuran; hexane at -78 - 0℃; for 0.5h; Stage #3: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran; hexane; N,N-dimethyl-formamide at 70℃; for 4h; | |
83% | With copper(l) iodide; potassium carbonate; sodium sulfite In N,N-dimethyl-formamide at 30℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With copper(l) iodide; potassium carbonate; sodium sulfite In N,N-dimethyl-formamide at 30℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With copper(l) iodide; potassium carbonate; sodium sulfite In N,N-dimethyl-formamide at 30℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.2% | With CuI In tetrahydrofuran | 40 Synthesis of farnesylacetone STR95 EXAMPLE 40 Synthesis of farnesylacetone STR95 The same procedure as that described in Example 25 was repeated except that 0.73 g of metallic magnesium, 80 ml of tetrahydrofuran, three droplets of ethylene dibromide, 7.4 g (0.03 mol) of geranyl chloride having a purity of 70%, 4.1 g (0.03 mol) of anhydrous zinc chloride, 0.2 g of CuI, 3 g (0.02 mol) of 3-chloromethylheptenone and 30 ml of tetrahydrofuran were used. Thus, 4.1 g of the objective compound was obtained as a colorless liquid (yield: 78.2%, purity: 98.8%). The obtained compound was catalytically reduced into phytone to determine the α-adduct content by GLC. The content was 0.3% by below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.1% | With CuI In tetrahydrofuran | 45 Synthesis of 3-methylene-7,11,15-trimethyl-1,6,10(E)-hexadecatriene STR100 EXAMPLE 45 Synthesis of 3-methylene-7,11,15-trimethyl-1,6,10(E)-hexadecatriene STR100 The same procedure as that described in Example 25 was repeated except that 0.73 g of metallic magnesium, 80 ml of tetrahydrofuran, three droplets of ethylene dibromide, 6.55 g (0.03 mol) of 6,7-dihydrogeranyl chloride, 2.7 g (0.02 mol) of anhydrous zinc chloride, 0.2 g (1.05 mmol) of CuI, 4.4 g (0.02 mol) of 3-chloro-6-methylene-2-methyl-octadiene-1,7 and 30 ml of tetrahydrofuran were used. Thus, 5.0 g of the objective compound was obtained as a colorless liquid (yield: 91.1%, purity: 99.2%). The liquid had a ratio of the objective compound (γ-adduct) to an isomeric by-product (α-adduct) of 9.8:0.2 as determined by HPLC. The conversion was 99.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sulfuric acid; sodium sulfate In ethyl acetate; N,N-dimethyl-formamide | 1 EXAMPLE 1 STR13 EXAMPLE 1 STR13 346 mg (2 mmols) of geranyl chloride and 787 mg (6 mmols) of N-ethylmorpholine N-oxide were placed in a flask, to which was further added 3 ml of N,N-dimethylformamide. The mixture was agitated at room temperature for 1 hour and at 50° C. for 4 hours. To the reaction mixture was added 10 ml of 2.5% sulfuric acid and 10 ml of ethyl acetate for phase separation. The resultant organic phase was washed with 5 ml of 2.5% sulfuric acid, 5 ml of a saturated sodium hydrogen carbonate aqueous solution and 5 ml of a 10% sodium sulfate aqueous solution successively, after which it was dried with magnesium sulfate. After the drying, the solvent was distilled off from the solution and the residue was subjected to distillation by the use of Kugel-rohr distillation apparatus (bath temperature 93° C./3 Torr.) to obtain 268 mg (1.76 mmols) of citral. The yield was 88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sulfuric acid In ethyl acetate; N,N-dimethyl-formamide | 23 EXAMPLE 23 STR27 EXAMPLE 23 STR27 330 mg (1.9 mmols) of a mixture of gernayl chloride, neryl chloride and linalyl chloride (ratios=61:32:7), 24.3 mg (0.25 mmols) of copper(I) chloride, 0.82 g (6.0 mmols) of triethylamine N-oxide (water content of 14%), and 3 ml of N,N-dimethylformamide were mixed and agitated at 45° C. for 2 hours. 15 ml of ethyl acetate and 8 ml of 2% sulfuric acid were added to the mixture and shaked sufficiently to extract an organic matter. The organic phase was collected, to which 145 mg of n-tetradecane was added, followed by subjecting to gas chromatography. As a result, it was found that starting geranyl chloride, neryl chloride and linalyl chloride disappeared with citral being formed at a yield of 67%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With chlorine In pentane | 13 EXAMPLE 13 EXAMPLE 13 The procedure employs an apparatus identical to that described in Example 12. Geranyl chloride (25.9 g; 0.15 mole) and dry pentane (60 cc) are introduced. The reaction mixture is heated to 37° C. and then gaseous chlorine diluted with argon is introduced, the distilled pentane being replaced with fresh pentane so as to keep the level constant in the reactor. After 3 hours 360 cc of pentane have been distilled and added and 10.6 g (0.15 mole) of chlorine have been added. After evaporation of the solvent a crude product (30.6 g) is obtained which is rapidly distilled at 95° C. under reduced pressure (0.5 mm Hg; 0.067 kPa). Analysis of the distillate by gas phase chromatography and by proton nuclear magnetic resonance spectrum shows that the degree of conversion of the geranyl chloride is 65% and that 3,8-dichloro-2,6-dimethyl-1,6-octadiene is obtained in a yield of 91% based on the converted geranyl chloride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(II) bis(trifluoromethanesulfonate); potassium carbonate In water at 20℃; for 12h; | |
174 mg | With potassium carbonate In 1,4-dioxane; acetonitrile at 40℃; for 24h; | 4.5.1.9 Synthesis of N,N-Diethyl geranyl amine (E-44k) General procedure: Entry 2: Following general procedure IV (chapter 2.2.1) geraniol E-14 (1.00 mmol, 1.0 equiv) wasallowed to react with benzoyl chloride (1.20 mmol, 1.2 equiv) in the presence of FPyr (0.10 mmol,10 mol%) in dioxane (0.5 mL, 2 M) for 24 h at room temperature. Then MeCN (2.0 mL, dioxane/MeCN 1:4, 0.4 M), K2C03 (320 mg, 2.30 mmol, 2.3 equiv) and diethylamine (530 ilL, 5.00 mmol, 5.0 equiv) were added to the reaction mixture and the resulting suspension was stirred for 24 h at 40 °C. Chromatographic purification of the crude product (249 mg) on silica gel (mass of crude material/Si02 1:35) with Et20/NEt3/nPen 5:3:92 gave diethylgeranyl amine E-44k as a yellow oilin 86% yield (180 mg, 0.858 mmol).M (C,4H27N) = 209.37 g/mol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: (1S,2S,5R)-(+)-neomenthyl selenol With n-butyllithium In tetrahydrofuran at -25℃; for 0.5h; Inert atmosphere; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran at 0 - 50℃; for 1h; | 4.6.1 (1S,2S,5R)-(+)-Geranyl neomenthyl selenide 25 General procedure: 4.3 General procedure for the synthesis of allylic selenides: At first, n-BuLi (1.97 ml) was carefully added to the selenol (4.92 mmol) in anhydrous THF (8 ml) at -25 °C under an argon atmosphere. The solution was stirred for 0.5 h and E- or Z-cinnamyl chloride (0.75 g, 4.92 mmol) in anhydrous THF (8 ml) was added. The solution was then stirred for 0.5 h at 0 °C, and then 0.5 h at 50 °C. The reaction mixture was cooled and poured into water (10 ml). The solvent was evaporated and the reaction mixture was extracted with diethyl ether (3×25 ml). The combined ether layers were dried over anhydrous MgSO4, and the solvent was evaporated. The residue was purified by column chromatography, eluting with petroleum ether to give the pure selenide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.778 % de | With sodium hexamethyldisilazane In tetrahydrofuran at 30℃; for 2.5h; Inert atmosphere; Overall yield = 56 %; Overall yield = 48 mg; | Synthesis of ketone 25 Into a flame-dried flask were added ketone 24 (63 mg, 0.181 mmol, 1 equiv), geranylchloride (14, 78 mg, 0.453 mmol, 2.5 equiv), and toluene (5 mL). Volatiles were removed under reduced pressure to remove any traces of water. The flask was fitted with a condensing column, capped with a rubber septum, and maintained under a nitrogen atmosphere. THF (0.10 mL, 2 M) was added, and the mixture was warmed to 30 C in a water bath. Sodium bis(trimethylsilyl)amide (1.0 M in THF, 0.27 mL, 0.27 mmol, 1.5 equiv) was added dropwise (over 1.5 h). The mixture was stirred (additional 1 h), quenched with potassium phosphate monobasic (1 M aqueous, 5 mL, producing pH = 5), and extracted with EtOAc (3 x 5 mL). The combined organic phases were washed with brine (8 mL) and dried with sodium sulfate. Volatiles were removed under reduced pressure and the crude material was purified via column chromatography (18 mL silica gel, 6:1 hexane/EtOAc) to yield ketone 25 (48 mg, 0.102 mmol, 56% yield, colorless oil) as a mixture of epimers at the CH-OMOM stereocenter (8:1 25A /25B). An aliquot of each epimer was isolated by column chromatography. 1H NMR signals were assigned by 1H-1H COSY. Stereochemistry of each epimer was assigned by 1H-1H NOESY. No other stereoisomers, constitutionalisomers, or double-alkylation products were observed by NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With N-benzyl-N,N,N-triethylammonium chloride; potassium hydroxide In N,N-dimethyl-formamide at 80 - 100℃; | Diethyl malonate derivatives 4 and 9 (general procedure). General procedure: A mixture of diethyl cyclohexylmalonate (2) (24.2 g, 0.1 mol) and corresponding alkylating agent 3 or 8 (0.1 mol) was gradually added to a suspension of powdered KOH (5.6 g, 0.1 mol) and BnNEt3Cl (5 mmol) in DMF (30 ml) at 80-85oC with stirring. The reaction mixture was stirred for additional 5-6 h at 95-100oC and cooled to ambient temperature (TLC-monitoring). The precipitate was filtered off and washed with diethyl ether (2×20 ml). The combined filtrates were evaporated under reduced pressure (40 torr, 40) to a minimum volume and the residue was diluted with Et2O (50 mL). The ether solution was washed with water (3×30 ml) and dried over anhydrous MgSO4. The solvent was evaporated (40 torr, 40) and the remaining oil was distilled in vacuo (0.5 torr) to afford compound 4 or 9 and unchanged starting compounds 2 and 3. Diethyl [(2E)-3,7-dimethylocta-2,6-dien-1-yl](cyclohexyl)malonate (4). A colourless oil, 21.3 g, yield 56% (86% calculated on the consumed starting materials), b.p. 175-180 (0.5 torr); nD20 1.4790 [Lit.S1: b.p. 161-169 (0.3 torr); nD25 1.4795]. 1H-NMR: δ 0.85-1.00 (m, 4H, 2CH2);1.25 (t, 6, 2Me, J 7.1 Hz); 1.30-1.40 (m, 2H, CH2); 1.55-1.75 (m, 4H, 2CH2); 1.60, 1.62, 1.68 (all s, 3 each, Me); 1.90-2.10 (m, 6H, 3CH2); 2.64 (m, H, CH); 4.12 (q, 4, 22, J 7.1 Hz); 5.06 (m, 1H, CH=); 5.08 (m, 1H, CH=) (see ref.S5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.3% | With tris(tetrabutylammonium) hydrogen pyrophosphate In acetonitrile at 20℃; for 2h; Inert atmosphere; | |
With tris(tetra-n-butylammonium) hydrogen pyrophosphate In acetonitrile at 20℃; Inert atmosphere; | ||
1.55 g | Stage #1: 1-chloro-3,7-dimethylocta-2,6-diene With tris(tetra-n-butylammonium) hydrogen pyrophosphate In acetonitrile at 20℃; for 2h; Stage #2: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With barium In tetrahydrofuran at 70℃; for 12h; Inert atmosphere; Schlenk technique; stereoselective reaction; | General Experimental Procedure for Allylation of Isatin Imines Using MetallicBarium (Entry 6 in Table 1; Tables 2-4; Entries 1 and 3 in Table 5): General procedure: Freshly cut barium (small pieces, 1.0 mmol) was placed in a Schlenk tube (50 mL) under an argon atmosphere and covered with dry THF (1 mL). The mixture underwentultrasonication for 30 min and THF was removed through a cannula under an argonstream. The resulting barium pieces were vigorously stirred under reduced pressureuntil they turned to powder. Then, a solution of allylic chloride (2, 1.0 mmol) andisatin imine 1 (0.25 mmol) in THF (4 mL) was added to the resulting barium powder atroom temperature under an argon atmosphere. After being heated to 70 °C, themixture was stirred for 12 h at this temperature and concentrated in vacuo after filtrationthrough a celite pad. The residual crude product was purified by columnchromatography on silica gel (hexane-EtOAc, 9:1) to afford 3-allylated3-amino-2-oxindole 3. The chemical yield was determined by 1H NMR using1,4-bis(trimethylsilyl)benzene as an internal standard. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.3% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.8% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47.6% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.6% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.4% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29.2% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25.8% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.1% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.1% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59.2% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20.3% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.5% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.5% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38.2% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49.2% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39.1% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52.8% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39.2% | With potassium carbonate In acetonitrile for 5h; Reflux; | 3.2.3. General Procedure of EβF Analogues 4a-4t General procedure: All the EβF analogues were synthesized according to the reported method [29]. Intermediate 2 (2.58 mmol), intermediate 3 (2.58 mmol) as prepared in Sections 3.2.1 and 3.2.2 and dried K2CO3 (2.58 mmol) were added to dried acetonitrile (20 mL) in a 100 mL round bottom flask. The mixture was refluxed for 5 h and then cooled to room temperature, filtered and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (petroleum ether/ethylacetate = 4:1) to give the EβF analogues 4a-4t. The yields, physicochemical properties and structural characterization data of 4a-4t were as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecyl-N,N-dimethylamine N-oxide; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 4h; | Preparation of N-geranyl-substituted anilines (7a-7t). General procedure: Yields: 39-83%. Take N-geranyl-aniline (7a) for example. To a mixture of aniline (1.12g, 12 mmol), KI (0.08g, 0.4 mmol), K2CO3(0.56g, 4 mmol), DDAO (9.16g, 12 mmol), and CH3CN (20 mL), the solution of geranyl chloride (0.70g, 4 mmol) in CH3CN was gently added in 20min. The resulting mixture was stirred 4h under room temperature. Then poured into 30 mL water and extracted with dichloromethane (2×30 mL), organic layer was combined and dried over anhydrous MgSO4and concentrated in vacuo. The resulting residue was purified by column chromatography on silica-gel column (petroleum ether: ethyl acetate = 4:1, v/v) to obtain the product 7a, yellow liquid, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | Stage #1: 2-bromo-pyridine With TurboGrignard In tetrahydrofuran at 0℃; for 3h; Schlenk technique; Inert atmosphere; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran at 0 - 25℃; for 12h; Schlenk technique; Inert atmosphere; regioselective reaction; | C. General Procedure of Compound 3 General procedure: A dry and nitrogen-flushed 25 ml Schlenk tube equipped with a magnetic stirrer and a septum was charged with a solution of 2-bromopyridine (1 mmol, 1.0 equiv) in dry THF (3 mL). i-PrMgClLiCl (2.1 mmol, 1.0 S3 M in THF, 2.1 equiv) was then added dropwise at 0 °C. After the reaction mixture was continuously stirred at 0 °C for 3 h, a complete Br/Mg exchange was observed as indicated by thin layer chromatography (TLC). Allylic chloride (3.0 mmol, 3.0 equiv) was added at 0 °C and the resulting mixture was gradually raised to room temperature, and stirred overnight. The resulting mixture was quenched with water (10 mL) and extracted with ethyl acetate (3 30 mL). The organic fractions were dried over Na2SO4, concentrated in vacuo and purified by silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 2-(3-methylbut-2-en-1-yl)pyridine With TurboGrignard In tetrahydrofuran at 0℃; for 5h; Schlenk technique; Inert atmosphere; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran at 0 - 25℃; for 12h; Schlenk technique; Inert atmosphere; | E. General Procedure of Compound 4 General procedure: General Procedure D: A dry and nitrogen-flushed 25 ml Schlenk tube equipped with a magnetic stirrer and a septum was charged with a solution of 2-(3-methylbut-2-en-1-yl)pyridine (1 mmol, 1.0 equiv) in dry THF (3 mL). i-PrMgClLiCl (1.1 mmol, 1.0 M in THF, 1.1 equiv) was then added dropwise at 0 °C. After the reaction mixture was continuously stirred at 0 °C for 5 h, allyl chlorides (1.5 mmol, 1.5 equiv) was added at S15 0 °C and stirred overnight at room temperature. The resulting mixture was quenched with water (10 mL) and extracted with ethyl acetate (3 30 mL). The organic fractions were dried over Na2SO4, concentrated in vacuo and purified by silica gel chromatography. 2-(7-ethyl-2-methylnona-2,6-dien-4-yl)pyridine Prepared from 2-(3-methylbut-2-en-1-yl)pyridine (147 mg, 1.0 mmol) and 1-chloro-3-ethylpent-2-ene (3.0 mmol) according to the general procedure D. Purification via flash column chromatography (eluent: 20 : 1 to 10 : 1 Petroleum ether : EtOAc) gave 4a. Yield: 70%; yellow oil; Rf = 0.32 (10:1 Petroleum ether: EtOAc); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: ethyl 2-cyclohexylacetate With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.666667h; Inert atmosphere; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; | 3 Synthesis of racemic carboxylic acid ethyl esters rac-3a, rac-3b and rac-4 (General procedure) General procedure: Lithium diisopropylamide (LDA) was prepared by treating a stirred solution of diisopropylamine (0.53g, 5.2 mmol) in dry THF (25 mL) with 2.5 M n-butyllithium in hexane (2.1mL, 5.2 mmol) under argon at -78 °C. The resulting solution was warmed to -30 °C and then recooled to -78 °C. Ethyl cyclohexylacetate 2 (0.74 g, 4.35 mmol) in dry THF (2mL) was added dropwise to this solution via syringe over a 10 min. The mixture was stirred at -78 °C for 0.5 h. Then the corresponding allylic halide (5.2 mmol) in dry THF (2 mL) was syringed, and the mixture was stirred without external cooling until it reached ambient temperature. Diethyl ether (30 mL) was added and the mixture was washed successively with 1N HCl (2×10 mL), brine (2×10 mL) and water (2×10 mL). The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure (40 Torr). The residue was purified by column chromatography (silica gel, n-hexane/CH2Cl2 20:1 to 5:1) to afford the corresponding racemic ester. 4.2.1.1. Ethyl (E)-2-cyclohexyl-5,9-dimethyldeca-4,8-dienoate rac-3a. Colorless liquid, 0.80g (60%); IR (CHCl3, cm-1): 1740 (C=O); 1H NMR (300 MHz, CDCl3): δ 5.10-5.08 (m, 2H), 4.12 (q, J=6.0Hz, 2H), 2.30-1.97 (m, 6H), 1.84-1.49 (m, 6H), 1.69 (s, 3H), 1.61 (s, 6H), 1.30-0.93 (m, 6H), 1.26 (t, J=6.0Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 175.4, 136.6, 131.2, 124.2, 121.6, 59.7, 52.3, 39.9, 39.7, 30.9, 30.7, 28.0, 26.7, 26.4, 26.3, 26.3, 25.6, 17.6, 16.0, 14.4; HRMS (ESI) m/z calcd for C20H34NaO2+: 329.2451; found [M+Na]+ 329.2450. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 3-piperidin-1-yl-propane-1,2-diol With sodium hydride In tetrahydrofuran for 0.25h; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In tetrahydrofuran for 24h; Reflux; | General procedure for the preparation of compounds 6a-c General procedure: Sodium hydride (0.6 g, 25 mmol) was added to a solution of aminoglycerol 4a-c (10 mmol) in THF (20 ml) with stirring, and the resulting solution was additionally stirred for 15 min prior to the formation of the alcoholate. Then, a solution of geranyl chloride 5 (5.17 ml, 28 mmol) in THF (15 ml) was added dropwise, and the mixture was refluxed for 24 h. The flask was cooled to room temperature and ice-cold water (40 ml) was added. The resulting mixture was extracted with dichloromethane (3×20 ml), solvent was evaporated in vacuo. The residue was purified by column chromatography on silica gel with hexane-ethyl acetate (3 :1) (for 6a,b) and hexane-acetone (3:1) (for 6c) as eluents. The products were obtained as yellow (6a,c) or yellow-orange (6b) oil. 1-(2,3-Bisgeranyloxypropyl)piperidine 6c: yield 3.02 g (70%). 1H NMR (CDCl3) d: 1.60 (m, 6H, CH2CH2CH2), 1.66 (s, 6H, Me), 1.68 (m, 16H, Me, CH2N), 1.83 (m, 2H, CHCH2O), 2.09 (m, 10H, CH2CH2 and NCH2), 3.98 (d, 4H, OCH2, 3J 6.8 Hz), 5.08 (m, 2H, =CH), 5.26 (m, 1H, CH), 5.44 (m, 2H, =CH). 13C NMR (CDCl3) d: 16.48, 17.70, 23.03, 25.72, 26.39, 32.46, 39.63, 44.47, 45.50, 66.41, 113.30, 120.99, 121.54, 124.06,131.63, 140.03. IR (ν/cm-1): 3365 (=CH), 2967 (Me), 2928 (Me), 2857 (CH2), 1720 (=CH), 1670 (C=C), 1446 (=CH), 1376 (Me), 1256 (C-N),1140, 1065, 928 (C-O-C), 902 (=CH), 570 (=CH). MS (MALDI), m/z: 432.5 [M+H]+, 465.5 [M+Na]+, 469.5 [M+K]+ (calc., m/z: 431.4 [M]+). Found (%): C, 77.02; H, 10.98; N, 3.56. Calc. for C28H49NO2 (%): C, 77.90;H, 11.44; N, 3.24. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: carvacrol With potassium carbonate In acetone at 20℃; for 0.166667h; Stage #2: 1-chloro-3,7-dimethylocta-2,6-diene In acetone at 80℃; for 4h; | 3.1.35. Synthesis of WSCP18-20 General procedure: A solution of CAR (100 mg, 0.67 mmol) in dry acetone (4 mL)was added with K2CO3 (1.1 eq.), and the mixture was stirred for10 min at room temperature. The suitable alkylating agent (3,3-dimethylallyl chloride, geranyl chloride, or trans-farnesyl chloride(1.1 eq)was added to the mixture, whichwas stirred for 4 h at 80° C.After cooling, the required products were purified by chromatographyusing CH2Cl2/MeOH (95:5) as eluent. WSCP18e20 were obtainedas oils in 83-95% yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.4% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 8h; | 4.1.6. Synthesis of (E)-2-((3-((3,7-dimethylocta-2,6-dien-1-yl)oxy)phenyl)amino)-4H-benzo[d][1,3]oxazin-4-one (42) The phenolic intermediate 2 (0.1 g, 0.39 mmol) was dissolved inDMF and to that potassium carbonate (0.163 g, 1.18 mmol) wasadded under stirring condition. Then Geranylchloride (0.087 mL,0.47 mmol) was added and the reaction mass was heated at 70 Cfor 8 h. After completion of reaction (checked by TLC), the reactionmasswas added intowater and extracted with ethyl acetate (3 30mL). Then the combined organic layer was washed with waterfollowed by brine solution. It was dried over sodium sulfate andevaporated. The compound was purified by column chromatographywhere the product was eluted at 30% ethyl acetate in hexanes.Yield: 0.098 g, 64.4%, white solid, m.p: 178e180 C. 1H NMR(300 MHz, CDCl3): d 1.63e1.64 (m, 6H), 1.84 (s, 3H), 2.01e2.09 (m,4H), 4.81 (d, J 6.0 Hz, 2H), 5.02 (t, J 6.6 Hz, 1H), 5.22 (t, J 6.0 Hz,1H), 6.49 (bs, 1 NeH), 6.63 (t, J 2.1 Hz, 1ArH), 6.79 (td, J 1.8,7.8 Hz, 2 ArH), 7.21e7.29 (m, 1ArH), 7.30e7.35 (m, 2ArH), 7.71 (td,J 1.5, 7.5 Hz, 1ArH), 8.27 (dd, J 1.5, 7.8 Hz, 1ArH) 13C NMR(100 MHz, CDCl3): d 16.9, 17.9, 25.9, 26.4, 39.7, 42.7, 114.6, 116.0,116.2, 116.7, 118.3, 119.9, 123.4, 123.8, 129.7, 130.5, 132.1, 135.7, 136.2,140.5, 140.8, 151.1, 157.7, 162.4. HRMS (ESI): m/z calculated forC24H27N2O3 [MH]: 391.2022; found: 391.2026. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Geraniol (0.5 g, 3.3 mmol) was added to the pre-cooled dichloromethane solution of 5 ml of thionyl chloride in an ice bath, stirred well, and then heated to reflux for 1 h.The reaction solution was evaporated under reduced pressure to remove excess thionyl chloride, the resulting brown oil was dissolved in 20 ml of THF, and the raw material ester (1 equivalent), anhydrous potassium carbonate (3 equivalent), and the catalytic amount KI were added.Heat to 60 C to react for 8 h, filter, and evaporate the solvent under reduced pressure. The residue is dissolved in 30 ml of water, extracted with ethyl acetate (20 ml × 3), and the organic phases are combined.Wash with saturated brine (15 ml × 2), dry with anhydrous sodium sulfate, filter,The filtrate was evaporated under reduced pressure to remove the solvent, and the residue was purified by column chromatography (petroleum ether/ethyl acetate, 5:1, v/v) to obtain a white solid, which was dissolved in 4 mL tetrahydrofuran, 6 mL methanol and 2 mL water.Add LiOH (2 equivalents), react at room temperature for 8 hours, distill off tetrahydrofuran and methanol under reduced pressure,Add 1N dilute hydrochloric acid dropwise under the ice water bath to adjust the PH 2-3, and a white solid precipitated out, filtered by suction,After drying, a white powdery solid compound II with 99% ee was obtained. |
Tags: 5389-87-7 synthesis path| 5389-87-7 SDS| 5389-87-7 COA| 5389-87-7 purity| 5389-87-7 application| 5389-87-7 NMR| 5389-87-7 COA| 5389-87-7 structure
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P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
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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