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CAS No. : | 763-32-6 | MDL No. : | MFCD00002933 |
Formula : | C5H10O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CPJRRXSHAYUTGL-UHFFFAOYSA-N |
M.W : | 86.13 | Pubchem ID : | 12988 |
Synonyms : |
|
Num. heavy atoms : | 6 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.6 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 26.84 |
TPSA : | 20.23 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) : | -5.92 cm/s |
Log Po/w (iLOGP) : | 1.66 |
Log Po/w (XLOGP3) : | 1.27 |
Log Po/w (WLOGP) : | 0.94 |
Log Po/w (MLOGP) : | 1.01 |
Log Po/w (SILICOS-IT) : | 0.69 |
Consensus Log Po/w : | 1.11 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.04 |
Solubility : | 7.82 mg/ml ; 0.0908 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.29 |
Solubility : | 4.38 mg/ml ; 0.0508 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.84 |
Solubility : | 12.4 mg/ml ; 0.144 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.43 |
Signal Word: | Danger | Class: | 3,8 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P280-P303+P361+P353-P305+P351+P338+P310-P370+P378-P403+P235-P501 | UN#: | 2924 |
Hazard Statements: | H226-H318 | Packing Group: | Ⅲ |
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 |
---|---|---|
43% | Stage #1: 2-methyl-1-buten-4-ol With tetrabutylammonium dihydrogen phosphate; trichloroacetonitrile In acetonitrile at 20℃; for 2h; Stage #2: With ammonium hydroxide In water | Typical experimental procedure General procedure: To a solution of the alcohol (1 mmol) in acetonitrile (1 mL), trichloroacetonitrile (2.4 mmol) is added, followed by dropwise addition of tetrabutylammonium dihydrogenphosphate (2.0 mmol) in acetonitrile (5 mL). The reaction mixture is stirred at room temperature for two hours, or until all the starting material is consumed. The solvent is removed in vacuo and the crude material is pre-purified by flash chromatography on silica gel (isopropanol/conc. aq NH4OH/H2O 7:2:1). The column fractions which show the presence of phosphate on TLC (e.g., with molybdate reagent) are combined and concentrated under reduced pressure. A Dowex 50WX8 ion-exchange column of 8 cm tall and 1 cm diameter is loaded and equilibrated with a mixture of conc. NH4OH/H2O 3:1 and afterward flushed with a buffer solution of 0.025 M NH4HCO3 until the pH reaches 8.0. The silica column residue is percolated through the DOWEX column with the same NH4OH buffer, collected, and dried either by lyophilization or by evaporation under reduced pressure until excess ammonium hydrogen carbonate is evaporated. The residual ammonium organophosphates are isolated as white solids |
With chloroform; triethylamine; trichlorophosphate anschliessendes Behandeln mit Wasser; | ||
With phosphonic Acid; iodine; triethylamine |
Stage #1: 2-methyl-1-buten-4-ol With trichloroacetonitrile at 20℃; for 0.0833333h; Stage #2: With phosphoric acid; triethylamine In acetonitrile at 37℃; | ||
With pyruvate kinase; Escherichia coli hydroxyethylthiazole kinase; ATP In aq. buffer at 20℃; for 16h; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In water at 280℃; for 0.166667h; | 1.A [Step A] Into a stainless steel-made reaction tube having an inside diameter of 2 mm and a length of 3,180 mm (internal volume: 10 mL) as heated at 280° C., a mixed solution of 2.4% by mass of formaldehyde, 2.4% by mass of water, 66.1% by mass of isobutene, and 29.1% by mass of tert-butyl alcohol (organic solvent) was fed at a rate of 1 mL/min. Here, an isobutene/tert-butyl alcohol/formaldehyde ratio (molar ratio) in the mixed solution is 15/5/1, and a retention time of the mixed solution is 10 minutes. An outlet of the reaction tube was connected to a condenser tube having an inside diameter of 2 mm and a length of 2,000 mm, and the reaction liquid was allowed to flow out while keeping an outlet pressure of the condenser tube at 20 MPa.The resulting reaction liquid was analyzed by means of gas chromatography. As a result, the conversion of formaldehyde was 81.6%, and the selectivity of 3-methyl-3-buten-1-ol was 90.5%. In addition, the contents of formic acid and a formic acid ester as byproducts were 1.4% and 0.8%, respectively.To 100 g of the reaction liquid obtained in the step A, a 1 mol/L sodium hydroxide aqueous solution was added in an amount of 12 mL (corresponding to 12 mmol of sodium hydroxide), and the mixture was stirred at 70° C. for 5 minutes. An organic layer (upper layer) was subjected to a gas chromatography analysis. As a result, all of formic acid and a formic acid ester of 3-methyl-3-buten-1-ol did not retain in the organic layer.An organic layer (upper layer) after alkali washing was subjected to purification by distillation under conditions of a theoretical plate number of 20, a reflux ratio of 1, a bath temperature of 140° C., and a pressure of 5.3 kPa. As a result, 3-methyl-3-buten-1-ol having a purity of 99.4% by mass was obtained at a distillation yield of 95.0%. |
at 200℃; | ||
In methanol; water; isopropyl alcohol |
at 100 - 110℃; | ||
at 150℃; for 8h; Gas phase; Inert atmosphere; | 2 48 g of catalyst (crushed D11-10 loaded with 50% by weight of EMIM TFSI and 10% by weight of AlCl3 based on the total supported catalyst) were installed in the gas-phase apparatus. At a reaction temperature of 150° C., 10 g/h (0.12 mol/h) of 36.5% strength formaldehyde solution (0.2 g/g of Cat/h), 5.4 standard liters/h (0.24 mol/h) of isobutene (introduced in gaseous form from a gas bottle) and 2 standard liters/h of N2 were passed through the apparatus. After a period of operation of 8 hours, the reaction output (condensed by means of a condenser and a cold trap at 0° C.) comprised isoprenol and isoprene in a ratio of 26.53:1.37 GC-% by area at an isobutene conversion of 5%. | |
With sodium methylate at 40 - 180℃; for 24h; Large scale; | 1 Example 1 The following operation was carried out using the continuous reaction apparatus shown in Fig.100% paraformaldehyde and 450 L of industrial sodium methoxide solution (3%) were added to the depolymerization vessel 2 dissolved in paraformaldehyde, and the mixture was heated to 40 ° C with stirring. The mixture was further stirred for 1 hour until paraformaldehyde was completely dissolved and then subjected to heat exchange 5 and 6, the material preheating, holding isobutylene and formaldehyde hemiacetal body molar ratio of 4: 1 ratio of the feed to the reactor tube 8, the feed to maintain airspeed 1.2H-1, maintaining the reaction temperature The reaction temperature is between 170 and 180 DEG C and the reaction pressure is between 9 and 10 MPa for 25 hours, and then the material enters the isobutene recovery tower 10. The isobutene is separated and cooled to -10 to -15 DEG C, And methanol was recovered for separation, and the bottom material flows into the product refining tower 12. The target product of rectification is 99.9%, the selectivity of 3-methyl-3-buten-1-ol is 99.2%, the product purity detected by gas chromatography of 99.6% formaldehyde content of less than 0.04%, a moisture content of less than 0.03%, the product structure has been characterized: | |
With europium(III) nitrate In water at 330℃; | 8 The temperature of the tubular reactor was set at 330 ° C,The reaction system pressure is 22MPa,The flow rate of 0.0005 wt% europium nitrate aqueous solution was 139. 8 g / min,37 wt% formaldehyde aqueous solution flow rate of 60 g / min, isobutene flow rate of 74. 59 g / min,The residence time of the reaction liquid in the reactor at this time was about 3 seconds.The conversion of formaldehyde was 98. 47% by liquid chromatography.Gas chromatographic analysis gave a selectivity of 3-methyl-3-buten-1-ol of 95.98%. (The mass ratio of europium nitrate to formaldehyde is 0. 00003: 1, the mass ratio of water to formaldehyde is 8: 1, the molar ratio of isobutene to formaldehyde is 1. 8: 1) | |
With aluminum trihydroxide; isopropyl alcohol at 200℃; for 1h; Autoclave; | 1 Synthesis of 3-methyl-3-buten-1-ol 58g administered paraformaldehyde, 200 g of isopropanol to a one-necked flask with a magnetic stirrer, stirred at 50 ~ 70 formaldehyde until dissolved, formaldehyde was obtained isopropanol solution. After continued stirring flask were added thereto 0.20g of aluminum hydroxide as a catalyst it has completely dissolved, then cooled to room temperature to give formaldehyde isopropanol solution was stored airtight mono vial, a solution of 20.2% formaldehyde content detection, content 0.08% aluminum hydroxide.Take isopropanol solution of formaldehyde 15g, 56g isobutylene, with mechanical stirring was charged to the autoclave, the reaction pressure 8MPa, held min in 200r / heating and stirring began, when the temperature reaches 200 start timing incubated for 1 hour. After cooling to room temperature, the autoclave was opened slowly eliminated isobutylene. The reaction was detected formaldehyde content, and do chromatography, mass spectrometry, in order to calculate the reaction selectivity and yield of formaldehyde as a reference.Through the above process was prepared methyl-3-buten-1-ol crude, recovered isobutylene, isopropanol prepared products recovered methyl-3-buten-1-ol. | |
In water; <i>tert</i>-butyl alcohol at 280℃; Flow reactor; Industrial scale; | 1 Into a stainless steel-made reaction tube having an inside diameter of 2 mm and a length of 3,180 mm (internal volume: 10 mL) and heated at 280° C., a mixed solution composed of 5.7 mass % of formaldehyde, 5.7 mass % of water, 74.5 mass % of isobutene, and 14.1 mass % of tert-butanol (organic solvent) was fed at a rate of 1 mL/min. Here, a molar ratio of isobutene to tert-butanol to formaldehyde in the mixed solution is 7/1/1. A residence time of the mixed solution is 10 minutes. An outlet of the reaction tube was connected to a cooling tube having an inside diameter of 2 mm and a length of 2,000 mm, an outlet pressure of the cooling tube was kept at 20 MPa, and a reaction liquid was allowed to flow out. | |
103.5 g | Stage #1: formaldehyd With acetaldehyde at 140℃; for 3h; Autoclave; Inert atmosphere; Stage #2: isobutene at 230℃; for 3h; Autoclave; Inert atmosphere; | 2 Example 2 Step 1, paraformaldehyde depolymerization:A mixture of 41.2 g of paraformaldehyde (95%And 180g of methylaldehyde were put into3L autoclave,With nitrogen replacement 2 to 3 times,Open stir and heat,The control temperature was 140 ° C,After 3 hours incubation cool down,Detection of non-solid precipitates in the depolymerization reactor,Showing a uniform transparent solution state.Step two, Prins reaction:800 g of isobutylene was weighed with a feeder,The isobutylene was pressed into the above-mentioned autoclave with 0.4 MPa of nitrogen,Open agitation,Heating up,The reaction temperature was controlled at 230 ° C,The reaction pressure is 15-16Mpa.After 3 hours of incubation, the cooling was cooled and the reaction material was released.Recycling of isobutene, the mother liquor distillation recovery of methylal,To give 103.5 g of 3-methyl-3-buten-1-ol,Content of 99.0%,The yield of paraformaldehyde was 92.4%. |
73 %Chromat. | With Sn-BEA zeolite In water; <i>tert</i>-butyl alcohol at 100℃; for 30h; | 1 Using the zeolitic material Sn-BEA according to Reference Example 2.1 as catalytically active material 55 g of an aqueous solution of formaldehyde (FA) (49 weight-%) were dissolved in 445 g of tert- butanol. A formaldehyde solution (5.39 weight-%) was obtained. This solution was dosed to an isothermal tubular reactor at 32 g/h (0.05 mol FA/h). The isobutene flask was pressurized with helium (to liquefy the gas) and pumped into the reactor at 31.3 g/h (0.55 mol/h). The two streams were pressurized to 20 bar and tempered to 100 °C before entering the reactor. The tubular reactor had a length of 110 cm and contained 10.85 g of a Sn-BEA catalyst according to Reference Example 2.1. The reactor was operated at 100 °C and at a constant pressure of 20 bar. The residence time was of about 15.67 min. The reaction was run for 48 h, and 4 samples were analysed during this time. After the reaction, the yield for 3-methyl-3-buten-1-ol based on the formaldehyde conversion was calculated with weight calibrated Gas Chromatography according to Reference Example 1.1. The unreacted formaldehyde was photometrically quantified according to Reference Example 1.1. The yield (Y), the selectivity (S) and the conversion (C) obtained are shown in Table 1 below. |
With chloroform at 100 - 110℃; | ||
With chloroform | ||
at 100 - 110℃; | ||
With Sn-BEA catalyst In water; <i>tert</i>-butyl alcohol at 100℃; for 48h; Inert atmosphere; | Reference Example 1.3: Synthesis of MBE in the high boiling solvent 2-ethlyhexanol 55 g of an aqueous solution of formaldehyde (FA) (49 weight-%) were dissolved in 445 g of tert- butanol. A formaldehyde solution (5.39 weight-%) was obtained. This solution was dosed to an isothermal tubular reactor at 32 g/h (0.05 mol FA/h). The isobutene flask was pressurized with helium (to liquefy the gas) and pumped into the reactor at 31.3 g/h (0.55 mol/h). The two streams were pressurized to 20 bar(abs) and tempered to 100 °C before entering the reactor. The tubular reactor had a length of 1 10 cm and contained 10.85 g of a Sn-BEA catalyst according to Reference Example 1.1. The reactor was operated at 100 °C and at a constant pressure of 20 bar(abs). The residence time was of about 15.67 min. The reaction was run for 48 h. The reaction mixture which was obtained was fed as stream F1 according to the invention to the inventive work-up process. In the following, this specific feed stream is denoted as (0411) Feed_K1200. The composition of the Feed_K1200 is given in Table 2 below. | |
In water; <i>tert</i>-butyl alcohol at 25 - 280℃; | 11 Example 11 An aqueous solution of 50 mass % formaldehyde (raw material liquid 1A) was fed into a stainless reactor tube (preheating tube 1) heated at 80° C. and having an inner diameter of 2 mm and a length of 50 mm (inner volume 0.1 mL) at 1.8 mL/hr and preheated therein. On the other hand, a mixture solution of 61.9 mass % of isobutene and 38.1 mass % of tert-butyl alcohol (raw material liquid 2E) was fed into a stainless reactor tube (preheating tube 2) at room temperature (25° C.) having an inner diameter of 2 mm and a length of 1545 mm (inner volume 4.9 mL) at 58.2 mL/hr. The amount of isobutene used for the reaction relative to 1 mol of formaldehyde was 15 mol, and the amount of tert-butyl alcohol used was 7 mol. The others than the above were the same as in Example 1, and according to the method, IPEA was produced. The production conditions and the results of analysis are shown in Table 1.According to the operation mentioned below, isobutene and formaldehyde were reacted to produce a γ,δ-unsaturated alcohol, 3-methyl-3-buten-1-ol (IPEA). During the production process, each operation was carried out while the pressure inside the reaction system was kept at 200 kg/cm2 (19.6 MPa). (0096) An aqueous solution of 50 mass % formaldehyde (raw material liquid 1A) was fed into a stainless reactor tube (preheating tube 1) preheated at 80° C. and having an inner diameter of 2 mm and a length of 125 mm (inner volume 0.4 mL) at 4.7 mL/hr and preheated therein. On the other hand, a mixture solution of 55.8 mass % of isobutene and 44.2 mass % of tert-butyl alcohol (raw material liquid 2A) was fed into a stainless reactor tube (preheating tube 2) at room temperature (25° C.) having an inner diameter of 2 mm and a length of 1465 mm (inner volume 4.6 mL) at 55.3 mL/hr. The amount of isobutene used relative to 1 mol of formaldehyde was 5 mol, and the amount of tert-butyl alcohol used was 3 mol. (0097) At the outlets of the preheating tubes, the raw material liquid 1A and the raw material liquid 2A were joined and contacted together, and the obtained mixture liquid was immediately fed to a stainless reaction tube (reactor) preheated at 280° C. and having an inner diameter of 2 mm and a length of 1590 mm (inner volume 5 mL) so that isobutene and formaldehyde were reacted in the reactor. The residence time of the each raw material liquid in the preheating tube was 5 minutes, and the residence time of the mixture liquid in the reactor was 5 minutes. The outlet of the reactor was connected to a condenser tube having an inner diameter of 2 mm and a length of 2,000 mm, and while the outlet pressure of the condenser tube was kept at 200 kg/cm2 (19.6 MPa), the reaction liquid was made to flow out. The obtained reaction liquid was analyzed through GC under the above-mentioned conditions, and the conversion ratio of formaldehyde was 88.1%, and the selectivity based on the formaldehyde equivalent of the targeted product γ,δ-unsaturated alcohol, 3-methyl-3-buten-1-ol (IPEA) was 84.5%. The production conditions and the results of analysis are shown in Table 1. | |
255 g | With hexamethylenetetramine In water at 270℃; for 1h; Autoclave; Inert atmosphere; Large scale; | 1 Example 1 2-Methylprop-l-ene (2053 g), aqueous formaldehyde (200 g; 50 wt.%) and 1.4 g urotropine were placed in an autoclave. The autoclave was sealed, stirred and heated to 270° C and thus the internal pressure rose to 100 bar. The autoclave was pressurized with nitrogen to 250 bar. The reaction mixture was stirred at 270° C and 250 bar for 1 h. The reaction mix ture was cooled to 25°C and the pressure was released. The 2-methylprop-l-ene was col lected and recycled. The liquid reaction mixture was weighted and analyzed. (0121) Organic upper phase: 370 g (0122) 69 % = 255 g 3-methyl-but-3-en-l-ol (0123) 0.9 % = 3.3 g formaldehyde (0124) 20.8 % = 77 g water (0125) 2 % = 7.4 g methanol (0126) 1.1 % = 4.1 g 3-methyl-but-3-en-l-yl formate (0127) 1.2 %= 4.4 3-methyl-but-2-enal (0128) 5 % = 5.5 g side-products (0129) Aqueous lower phase: 29 g (0130) 8 % = 2.3 g 3-methyl-but-3-en-l-ol (0131) 4 % = 1.16 g methanol (0132) 2 % = 0.56 g side products (0133) 86 % = 24.9 g water |
257.3 g | With hexamethylenetetramine In water at 25 - 270℃; for 1h; Autoclave; Large scale; | 1a; 1b 2-Methylprop-l-ene (2053 g), aqueous formaldehyde (200 g; 50 wt.%) and 1.4 g urotropine were placed in an autoclave. The autoclave was sealed, stirred and heated to 270° C and thus the internal pressure rose to 100 bar. The autoclave was pressurized with nitrogen to 250 bar. The reaction mixture was stirred at 270° C and 250 bar for 1 h. The reaction mix ture was cooled to 25 °C and the pressure was released. The 2-methylprop-l-ene stream was collected, water was separated and 2-methylprop-l-ene recycled. The liquid reaction mixture was weighted and analyzed.; Organic upper phase: 370 g69 % = 255 g 3- methyl -but-3-en-l-ol0.9 % = 3.3 g formaldehyde20.8 % = 11 g water2 % = 7.4 g methanol1.1 % = 4.1 g 3-methyl-but-3-en-l-yl formate1.2 %= 4.4 3-methyl-but-2-enal5 % = 5.5 g mixture of C6-diols = (Z)-3-methylpent-2-ene-l,5-diol, (E)-3-methylpent- 2-ene-l,5-diol and 3-methylenepentane-l,5-diol; Aqueous lower phase: 29 g, 8 % = 2.3 g 3-methyl-but-3-en-l-ol4 % = 1.16 g methanol 2 % = 0.56 g side products 86 % = 24.9 g water. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: 2-methyl-1-buten-4-ol With diethylzinc(II) In hexane at 0 - 15℃; for 0.833333h; Stage #2: diiodomethane In dichloromethane at 25℃; for 20h; | 148.1 Step 1: 2-(1-Methylcyclopropyl)ethanol To a solution of diethylzinc (hexane solution) (2 L of 1 M, 2.0000 mol) was added 3- methylbut-3-en-1-ol (135 g, 1.5674 mol) at 0 - 15 °C in 30 minutes. The mixture was then warmed to 15 °C and after 20 minutes of stirring, diiodomethane (482.7 g, 1.8022 mol) as a DCM (270 mL) solution was added over 1 h. The reaction was then warmed to 25 °C and stirred for 20 hours. After cooling to 5 °C, the reaction mixture was quenched with aqueous HCl (2 M, 1.35 L). The phases were split, and the aqueous phase extracted with DCM (2x 675 mL). The hexanes extract was, washed with sodium thiosulfate (10% w/w, 1.35 L), and concentrated in vacuo. The sodium thiosulfate solution was then extracted with the two DCM extracts successively. The DCM extracts were then combined with the product obtained from the concentration of the hexanes extract. Water (1.35 L) was then added to this combined organic phase. The mixture was cooled to 2 °C and an aqueous solution of sodium permanganate (83.5 g, 40 %w/w, 235.34 mmol) was added. The mixture was stirred at 2 °C for 15 minutes, sodium bisulfite (10% w/w, 1 L) was added, the phases were split and the aqueous phase washed with DCM (2x 350 mL). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated in vacuo and distilled (40°C, 2-5 mbar) to give 2-(1-methylcyclopropyl)ethanol (106.6 g, 66%) as a clear oil.1H NMR (400 MHz, CDCl3) δ 3.75 (t, J = 7.0 Hz, 2H), 1.51 (t, J = 7.0 Hz, 3H), 1.04 (s, 3H), 0.32 - 0.22 (m, 4H). |
52% | With diethylzinc(II) In dichloromethane at -10 - 20℃; for 13h; Inert atmosphere; | 10.A Example 10 3-(2-chlorophenyl)sulfanyl-6-[6-[2-(l-methylcyclopropyl)ethoxy]-2-pyridyl]-6-(3-thienyl)pipe ridine-2,4-dione Example 10 3-(2-chlorophenyl)sulfanyl-6-[6-[2-(l-methylcyclopropyl)ethoxy]-2-pyridyl]-6-(3-thienyl)pipe ridine-2,4-dione 10 Step A: Diethylzinc (40.6 ml, 40.6 mmol) and diiodomethane (9.3 g, 34.8 mmol) was added to a solution of 3-methylbut-3-en-l -ol (1 g, 11.6 mmlo) in DCM (80 mL) at -10 °C. The reaction mixture was stirred at 0 °C for 1 hour and then room temperature for additional 12 hours. The reaction was quenched with saturated NH4C1, extracted with DCM (50 mL x 2), dried over anhydrous Na2S04 and concentrated to afford 2-(l-methylcyclopropyl)ethanol (600 mg, 6 mmol, 52% yield) as light color oil. Step B: 5-((2-Chlorophenyl)thio)-4-hydroxy-6'-(2-(l -methylcyclopropyl)ethoxy)- 2-(thiophen-3-yl)-2,3-dihydro-[2,2'-bipyridin]-6(lH)-one was prepared in 39% yield according to the Example 2, Step A substituting propan-2-ol for 2-(l-methylcyclopropyl)ethanol. Mixture of diastereoisomers: lH NMR (400MHz, CD3OD) δ 7.74 (dd, J= 8.0, 8.0 Hz, IH), 7.47 (dd, J = 5.2, 3.2 Hz, IH), 7.30 - 7.15 (m, 4H), 6.96 (dd, J= 8.0, 8.0 Hz, IH), 6.77 - 6.75 (m, 2H), 6.01 (dd, J= 8.4, 1.6 Hz, IH), 4.49 (t, J= 7.2 Hz, 2H), 3.93 (d, J= 16.0 Ηζ,ΙΗ), 3.48 (d, J= 16.4 Ηζ,ΙΗ), 1.70 (t, J= 6.8 Hz, 2H), 1.09 (s, 3H), 0.34 - 0.23 (m, 4H). Stereoisomer 1 : lH NMR (400MHz, CD3OD) δ 7.50 (dd, J= 8.0, 8.0 Hz, IH), 7.48 (dd, J= 5.2, 3.2 Hz, IH), 7.30 - 7.22 (m, 2H), 7.06 - 7.00 (m, 2H), 6.93 (dd, J= 8.0, 8.0 Hz, IH), 6.54 - 6.52 (m, 2H), 5.79 (dd, J= 8.0, 1.6 Hz, IH), 4.26 (t, J= 6.8 Hz, 2H), 3.70 (d, J= 16.0 Ηζ,ΙΗ), 3.25 (d, J= 16.4 Ηζ,ΙΗ), 1.46 (t, J = 6.8 Hz, 2H), 0.86 (s, 3H), 0.11 - 0.00 (m, 4H). Stereoisomer 2: 1H NMR (400MHz, CD3OD) δ 7.48 (dd, J= 8.0, 8.0 Hz, lH), 7.46 (dd, J= 5.2, 3.2 Hz, 1H), 7.21 - 7.20 (m, 2H), 7.05 - 7.03 (m, 2H), 6.93 (dd, J= 8.0, 8.0 Hz, 1H), 6.53 - 6.50 (m, 2H), 5.77 (dd, J= 8.0, 1.6 Hz, 1H), 4.24 (t, J= 6.8 Hz, 2H), 3.68 (d, J= 16.0 Ηζ,ΙΗ), 3.23 (d, J= 16.4 Ηζ,ΙΗ), 1.45 (t, J= 6.8 Hz, 2H), 0.85 (s, 3H), 0.10 - 0.01 (m, 4H). |
52% | With diethylzinc(II) In dichloromethane at -10 - 20℃; for 13h; | 10.A Step A: Diethylzinc (40.6 ml, 40.6 mmol) and diiodomethane (9.3 g, 34.8 mmol) was added to a solution of 3-methylbut-3-en-l-ol (1 g, 11.6 mmol) in DCM (80 niL) at -10 °C. The reaction mixture was stirred at 0 °C for 1 hour and then room temperature for additional 12 hours. The reaction was quenched with saturated NH4C1, extracted with DCM (50 rriL x 2), dried over anhydrous Na2S04 and concentrated to afford 2-(l-methylcyclopropyl)ethanol (600 mg, 6 mmol, 52% yield) as light color oil. |
With copper atom; zinc In diethyl ether Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.1% | With thionyl chloride; triethylamine at 5 - 65℃; for 6h; | Synthesis of 3-methyl-3-butenyl chloride A 1 L reactor equipped with a stirrer, a thermometer and a dropping funnel was charged with 3-methyl-3-butene-1-ol 66.0 g (0.697 mol) of 270 ml of diethylene glycol dibutyl ether and 77.5 g (0.767 mol) of triethylamine were charged and cooled to an internal temperature of 5 ° C. or less with stirring. 91.2 g (0.767 mol) of thionyl chloride was added dropwise while keeping the internal temperature at 10 ° C. or less, and after completion of the dropwise addition, the temperature was raised to 65 ° C. and the mixture was heated and stirred for 6 hours. After completion of the reaction, the inner temperature was cooled to 30 ° C. or lower, 200 g of water was added, the reaction mixture was washed, and the organic phase was separated. The organic phase was washed with 500 g of a 5% sodium bicarbonate aqueous solution and then with 200 g of saturated brine successively. The washed organic phase was distilled under reduced pressure to obtain 46.0 g (0.440 mol: yield 63.1%) of 3-methyl-3-butenyl chloride. |
50% | With thionyl chloride; triethylamine In diethyl ether at 5 - 55℃; for 15.5h; | 3 Synthesis Example 43.06 g (0.50 mol) of 3-methyl-3-buten- 1 -ol, 55.65 g (0.55 mol) of triethylamine and 200 g of ether were charged in a 500-ml reactor equipped with a stirrer, a cooling tube, a thermometer and a dropping funnel, and the interior mixture was cooled down to 5° C. under stirring. Then, 65.43 g (0.55 mol) of thionyl chloride was dropwise charged over 2.5 hours while the internal temperature was held at 100 C. or lowet After the dropping, the resultant mixture was heated up to an internal temperature of 50 to 550 C., and heated and stirred for 13 hours. Afier cooling, 125 g of water was added, stirred and allowed to stand; thereafier, a water phase was separated, and thrther an organic phase was washed with 130 g of a 5% sodium hydrogencarbonate aqueous solution and 125 g of watet The separated organic phase was obtained in 235.2 g, and analyzed by gas chromatography; as a result of the analysis, the organic phase contained 46.5 g (0.44 mol, yield: 88%) of 3-methyl-3- butenyl chloride. The reaction solution was distilled under reduced pressure to thereby obtain 23.3 g (distillation yield:50%) of 3-methyl-3-butenyl chloride (hereinafter, designated as IPEC) of 99% or higher in purity. |
With thionyl chloride; tributyl-amine |
With thionyl chloride; tributyl-amine In diethyl ether | ||
With thionyl chloride Heating; | ||
With tetrachloromethane; triphenylphosphine In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With N-Bromosuccinimide; triphenylphosphine In dichloromethane for 3h; Ambient temperature; | |
75% | With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 3h; | 52.A [0499] Step A. 4-bromo-2-methylbut-1-ene. To a mixture of 3-methyl-3-butene-l-ol (10.1 mL, 0.100 mol), and triphenylphosphine (28.8 g, 0.110 mol) in dry DCM (20 mL) at 0°C was added NBS (19.6 g, 0.110 mol) in portions. The mixture was stirred at r.t. for 3 hr then diluted with hexane (60 mL) and filtered through a short silica gel pad. The filtrate was distilled under reduced pressure to afford the desired product (55.9 g, 75% yield). |
75% | With N-Bromosuccinimide; triphenylphosphine at 20℃; Inert atmosphere; |
55% | With N-Bromosuccinimide; triphenylphosphine In dichloromethane for 2h; Ambient temperature; | |
50.6% | With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 23℃; for 2h; | |
40% | With N-Bromosuccinimide; triphenylphosphine In dichloromethane for 16h; | |
30% | With phosphorus tribromide In diethyl ether | |
29% | With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | To a 500 mL RBF, oven dried and under Ar, with stirbar and 10.0 mL (99.0 mmol, 1.0 equiv) of 3-methyl-3-butene-1-ol (51) in 33 mL of dry methylene chloride (3M) at 0° C was added 31.2 g of triphenylphosphine (119 mmol, 1.2 equiv). Then, 21.1 g of NBS (119 mmol, 1.2 equiv) was added portion-wise as this reaction is extremely exothermic. After stirring for 12 hrs and allowing the reaction to slowly warm to room temperature, the methylene chloride was removed in vacuo. Next, 250 mL of hexanes was added to the flask and allowed to stir for 15 min. Then, the solution was filtered through a pad of silica gel to remove the white solids, when the resulting filtrate was then concentrated. Finally, the crude mixture was then distilled at 115°C to give 4.15 g of 52 (29% yield) as a clear, colorless oil. All spectra were in accordance with known literature values. |
With pyridine; phosphorus tribromide | ||
With pyridine; phosphorus tribromide at 0℃; for 6h; | ||
With lithium bromide 1) --> mesylate, 2) DMF; Multistep reaction; | ||
With N-Bromosuccinimide; triphenylphosphine In tetrahydrofuran | ||
Multi-step reaction with 2 steps 1: 99 percent / Et3N / CH2Cl2 / 0.5 h / -5 °C 2: 100 percent / LiBr / dimethylformamide / 2 h / Heating | ||
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2 / 1 h / 0 - 20 °C 2: 9.86 g / LiBr / tetrahydrofuran / 12 h / Heating | ||
Multi-step reaction with 2 steps 1: 85 percent / pyridine / 16 h / 0 °C 2: 76 percent / LiBr / dimethylformamide / 24 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 91 percent / Et3N / CH2Cl2 / 0.25 h / 0 °C 2: 57 percent / LiBr / acetone / 15 h / Heating | ||
Multi-step reaction with 2 steps 1: triethylamine / CH2Cl2 2: lithium bromide / acetone | ||
2.95 g (26.4%) | With pyridine; phosphorus tribromide | 43.a a. a. 1-Bromo-3-methyl-3-butene The title compound was prepared by mixing 7.75 ml (75.0 mM) 3-methyl-3-buten-1-ol and 2.06 ml (25.5 mM) pyridine at -40° C. Slowly, to maintain the reaction temperature below -30° C., were added 2.40 ml (25.5 mM) phosphorus tribromide dropwise. Mechanical stirring was necessary as the reaction mixture became very thick. After warming to rt, the reaction mixture was stirred 3 hours, diluted with 20 ml Et2 O, washed three times with H2 O, 10 ml each, and dried over MgSO4. After filtration, the volatiles were distilled. Product was distilled to yield 2.95 g (26.4%) of a colorless liquid, bp=45° C. at 40 mm of Hg. |
With methanesulfonyl chloride; triethylamine; lithium bromide In dichloromethane | ||
With N-Bromosuccinimide; triphenylphosphine In tetrahydrofuran at 23℃; for 11h; Inert atmosphere; | ||
With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; Inert atmosphere; | ||
3.66 g | With N-Bromosuccinimide; triphenylphosphine In tetrahydrofuran at 20℃; for 11.25h; | |
Multi-step reaction with 2 steps 1: triethylamine / 0 - 20 °C 2: lithium bromide / tetrahydrofuran / Reflux | ||
With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 23℃; for 15h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine at 0℃; for 2.5h; | |
100% | With triethylamine In dichloromethane at 20℃; for 18h; | |
98% | With triethylamine In dichloromethane 1.) 0 deg C, 1 h, 2.) r.t., 12 h; |
98% | With pyridine In dichloromethane at 0 - 20℃; for 15.25h; Inert atmosphere; | |
96% | With dmap In dichloromethane at 0 - 20℃; Inert atmosphere; | |
95% | With sodium hydroxide; benzyl-triethyl-ammonium chloride In dichloromethane for 0.333333h; Ambient temperature; | |
95% | With dmap In dichloromethane | |
94% | With pyridine In chloroform for 15h; Ambient temperature; | |
94% | In dichloromethane at 0℃; for 2h; | 2 Tosyl chloride (4.8 g, 25 mmol) and 4-(N, N-dimethylamino-) pyridine (3. 4 g, 27.5 mmol) were mixed under magnetic stirring with 90 ml of anhydrous dichloromethane in a 250-ml three-necked flask cooled in an ice bath. A solution of 3-methyl-3-buten-1-ol (2.2 g, 25 mmol) in about 10 ml of anhydrous dichloromethane was then slowly introduced with a syringe through a septum in the flask, and the ice bath was then removed. The reaction was monitored by silica gel TLC (pentane/ethyl acetate, 85: 15 (v/v)). After 2 h with constant stirring, the mixture was precipitated by dilution into 1 liter of hexane and filtered, and the filtrate was concentratedunder reduced pressure. This filtration/suspension step was repeated using diethyl ether, and the resulting oil was purified by liquid chromatography on silica gel (pentane/ethyl acetate, 85: 15 (v/v) ), yielding a yellow oil of 3-methyl-3-buten-1-yl-tosylate (5.6 g, 23.5 mmol, 94% yield) kept under dry N2 at 4 °C. |
94% | With dmap In dichloromethane at 0℃; for 2h; | 3 Tosyl chloride (4.8 g, 25 mmol) and 4-(N, N-dimethylamino-) pyridine (3.4 g, 27.5 mmol ; Aldrich) were mixed under magnetic stirring with 90 ml of anhydrous dichloromethane in a 250-ml three-necked flask cooled in an ice bath. A solution of 3-methyl-3- butene-1-ol (2.2 g, 25 mmol) in about 10 ml of anhydrous dichloromethane was then slowly introduced with a syringe through a septum in the flask, and the ice bath was then removed. The reaction was monitored by silica gel TLC (pentane/ethyl acetate, 85: 15 (v/v)). After 2 h with constant stirring, the mixture was precipitated by dilution into 1 liter of hexane and filtered, and the filtrate was concentrated under reduced pressure. This filtration/suspension step was repeated using diethyl ether, and the resulting oil was purified by liquid chromatography on silica gel (pentane/ethyl acetate, 85 : 15 (v/v) ), yielding a yellow oil of 3-methyl-3-butene-1-yl- tosylate (5.6 g, 23.5 mmol, 94% yield) kept under dry N2 at 4 °C (positive mode ESI-MS: m/z 241 [M + H] + ; mlz 258 [M + NH4] + ; mlz 263 [M + Na] + ; MS2 of m/z 258 : m/z 190 (C5H8 loss)). |
94% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | |
93% | With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere; | 3-Methyl-3-buten-1-yl p-toluenesulfonate (13) 3-Methyl-3-buten-1-ol (12, 12.5 g, 14.4 mL, 1.0 equiv, 145.3 mmol) was dissolved inDCM (150 mL), and the solution was cooled to 0 C. Pyridine (23.7 g, 24.2 mL, 2.05equiv, 300.0 mmol) was added in one portion, followed by dropwise addition of a solutionof p-toluenesulfonyl chloride (27.2 g, 0.98 equiv, 142.5 mmol) in DCM (50 mL) over20 min. The mixture was allowed to slowly warm to room temperature with stirringovernight. The crude reaction mixture was washed with water (3100 mL), aqueousNH4Cl (150 mL), aqueous NaCl (100 mL), and then dried (Na2SO4). The solvent wasremoved under vacuum to afford 13 (31.7 g, 93%) as a pale yellow liquid. The spectramatched those reported previously.18 |
91% | With dmap; triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere; | |
89% | With dmap In dichloromethane at 0 - 20℃; | |
89% | With pyridine at 0℃; for 2.5h; | 3.1 Synthesis of 3-methylbut-3-en-1-yl-4-methylbenzenesulfonate The alcohol (10 mL, 98.7 mmol) was dissolved in 50 mL pyridine and cooled to 0 °C. At this temperature, p-toluenesulfonyl chloride (TsCI, 21.8 g, 113.5 mmol, 1.15 equiv.) was added in small portions and stirred for 2.5 h at this temperature. It was warmed to room temperature and the reaction was terminated with 2M HCI solution (100 mL). The phases were separated and the aqueous phase was extracted with MTBE (2 x 100 mL). The combined organic phases were successively washed with 10% NH4CI solution (100 mL), 5% NaHCO3solution (100 mL) and saturated NaCI solution (100 mL). The organic phases were dried with Na2SC>4, filtered and the volatile components were removed under reduced pressure. The product was obtained as a colorless liquid (21.2 g, 88.2 mmol, 89%) and carried over to the next step without any purification.TLC: Rf= 0.49 (ethyl acetate/cyclohexane, 20:80)GC: DB-1 column: fa = 13.4 min1H-NMR (400 MHz, CDCh) 6 = 7.79 (d, J = 8.3 Hz, 2H, 2x ArH), 7.35 (d, J = 8.1 Hz, 1 H, 2x ArH), 4.79 (s, 1 H, C=C(H)H‘), 4.68 (s, 1 H, C=C(H)H‘), 4.13 (t, J = 6.9 Hz, 2H, CH2OTs), 2.45 (s, 3H, ArCH3), 2.35 (t, J = 6.8 Hz, 2H, C(=CH2)CH2), 1.66 (s, 3H, C(=CH2)CH3)13C-NMR (101 MHz, CDCh) 6 = 144.73 (CH3C(Ar)), 140.13 (C=CH2), 133.16 (SO2C(Ar)), 129.81 (2xAr), 127.91 (2x Ar), 113.10 (C=CH2), 68.54 (CH2OTs), 36.76 (C(=CH2)CH2), 22.34 C(=CH2)CH3), 21.65 (ArCH3)IR (GC/FT-IR): = 3084 (w), 2968 (m), 2937 (w), 1392 (m) 1188 (s), 1088 (m), 1025 (s), 973 (m) cm'1MS (El): m/z = 155 [Ts]+, 91 [(C6H4)CH3]+, 55 [(CH3)C(=CH2)CH2]+ |
89% | With pyridine at 0℃; for 2.5h; | 3.1 Synthesis of 3-methylbut-3-en-1-yl-4-methylbenzenesulfonate The alcohol (10 mL, 98.7 mmol) was dissolved in 50 mL pyridine and cooled to 0 °C. At this temperature, p-toluenesulfonyl chloride (TsCI, 21.8 g, 113.5 mmol, 1.15 equiv.) was added in small portions and stirred for 2.5 h at this temperature. It was warmed to room temperature and the reaction was terminated with 2M HCI solution (100 mL). The phases were separated and the aqueous phase was extracted with MTBE (2 x 100 mL). The combined organic phases were successively washed with 10% NH4CI solution (100 mL), 5% NaHCO3solution (100 mL) and saturated NaCI solution (100 mL). The organic phases were dried with Na2SC>4, filtered and the volatile components were removed under reduced pressure. The product was obtained as a colorless liquid (21.2 g, 88.2 mmol, 89%) and carried over to the next step without any purification.TLC: Rf= 0.49 (ethyl acetate/cyclohexane, 20:80)GC: DB-1 column: fa = 13.4 min1H-NMR (400 MHz, CDCh) 6 = 7.79 (d, J = 8.3 Hz, 2H, 2x ArH), 7.35 (d, J = 8.1 Hz, 1 H, 2x ArH), 4.79 (s, 1 H, C=C(H)H‘), 4.68 (s, 1 H, C=C(H)H‘), 4.13 (t, J = 6.9 Hz, 2H, CH2OTs), 2.45 (s, 3H, ArCH3), 2.35 (t, J = 6.8 Hz, 2H, C(=CH2)CH2), 1.66 (s, 3H, C(=CH2)CH3)13C-NMR (101 MHz, CDCh) 6 = 144.73 (CH3C(Ar)), 140.13 (C=CH2), 133.16 (SO2C(Ar)), 129.81 (2xAr), 127.91 (2x Ar), 113.10 (C=CH2), 68.54 (CH2OTs), 36.76 (C(=CH2)CH2), 22.34 C(=CH2)CH3), 21.65 (ArCH3)IR (GC/FT-IR): = 3084 (w), 2968 (m), 2937 (w), 1392 (m) 1188 (s), 1088 (m), 1025 (s), 973 (m) cm'1MS (El): m/z = 155 [Ts]+, 91 [(C6H4)CH3]+, 55 [(CH3)C(=CH2)CH2]+ |
86% | With pyridine In dichloromethane at 20℃; for 8h; | |
85% | With pyridine at 0℃; for 16h; | |
85% | With dmap In dichloromethane for 3h; | 1 EXAMPLE 1; Production of 3-(Bromomethyl)-3-butanol-1-yl Diphosphate (BrHPP); Preparation of 3-Methyl-3-butene-1-yl Tosylate (Isopentenyl Tosylate) 2.32 mmol (442 mg) of tosyl chloride and 2.55 mmol (312 mg) of 4-(N,N-dimethylamino)pyridine are introduced while stirring with a magnetic stirrer into 5 ml of anhydrous dichloromethane in a glass reaction vessel which is equipped for handling under an inert atmosphere and has been carefully dried. 2.32 mmol (200 mg) of isopentenol dissolved in approx. 1 ml of dichloromethane are slowly added to this mixture through a septum using a syringe. The reaction is monitored by thin-layer chromatography on silica (silica gel 60 F-254; eluent: pentane/ethyl acetate 85/15 vol./vol.; Rf (product)=0.4 and Rf (TsCl)=0.5). After approx. 3 hours' stirring under a nitrogen atmosphere, the reaction mixture is diluted in a large volume of hexane (approx. 100 ml), resulting in the immediate formation of a white precipitate. The mixture is then filtered and the filtrate concentrated by evaporation under reduced pressure. The solution is then diluted with diethyl ether and refiltered. Once the solvent has evaporated, a yellowish oil is obtained. The product is purified by preparative chromatography through a silica column (silica gel 60; eluent: pentane/ethyl acetate 85/15). In this manner, 1.98 mmol (475 mg) of 3-methyl-3-butene-1-yl tosylate (85% isolated yield) are obtained. The compound (colorless oil) is stored at +4° C. in an anhydrous medium. |
82% | With pyridine In chloroform Inert atmosphere; | |
80% | With dmap In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | |
79% | With pyridine In dichloromethane for 12h; Ambient temperature; | |
79% | Stage #1: p-toluenesulfonyl chloride With pyridine In dichloromethane for 0.0833333h; Cooling with ice; Stage #2: 2-methyl-1-buten-4-ol In dichloromethane at 20℃; Inert atmosphere; | |
79% | With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere; | |
77% | With triethylamine In dichloromethane at 20℃; for 18h; | |
75% | With dmap; triethylamine In dichloromethane at 0℃; for 48h; Inert atmosphere; | |
39% | With pyridine at 0℃; for 1h; | |
18% | With pyridine at 0 - 20℃; for 18h; | Synthesis of 3-methylbut-3-en-1-yl 4-methylbenzenesulfonate (6). The preparation ofcompound 6 was carried out according to a modified protocol reported in reference 30. In detail,at 0°C a solution of tosylchloride (18.47 g, 96.9 mmol) in dried pyridine (120 mL) was slowlyadded to solution of 3-methylbut-3-en-1-ol (97%, 10 mL, 96.9 mmol) in dried pyridine (50 mL) and after warming up to room temperature the resulting solution was stirred for 18h.Subsequently, saturated aqueous sodium bicarbonate (40 mL) was added, and the mixture wasstirred for 40 min. After removal of the solvent in vacuo, the residue was dissolved in chloroformand subsequently washed with diluted hydrochloric acid (2M, 20 mL), distilled water (40 mL)and saturated aqueous sodium bicarbonate (40 mL). The combined organic phases were driedover magnesium sulfate and after filtration the volatile components were removed in vacuo. Theresulting crude product was purified through column chromatography. The compound 6 wasobtained in 18% yield (3.90 g, 17.03 mmol, 98% purity). |
With pyridine | ||
With n-butyllithium 1) THF, hexane, 0 deg C, 2) 25 deg C, 3h; Yield given. Multistep reaction; | ||
With pyridine at 20℃; for 2h; | ||
In pyridine | ||
With pyridine | ||
In pyridine at 0℃; | ||
With pyridine at 0℃; | ||
With pyridine for 13h; Yield given; | ||
With pyridine; dmap at -10℃; for 5h; | ||
1.09 g | With dmap; calcium hydride In dichloromethane at 20℃; | |
With pyridine at 0℃; Inert atmosphere; | ||
244.5 g | With pyridine In toluene at 20℃; for 16h; Inert atmosphere; | 1.1 First step 3-methyl-3-buten-1-ol (100.0 g), pyridine (180 mL) under nitrogen atmosphere,While cooling to a mixture of toluene (400 mL)p-Toluenesulfonic acid chloride (243.5 g) was added and the mixture was stirred at room temperature for 16 hours. The precipitated salt was removed by vacuum filtration.Water (400 mL) and pyridine (100 mL) were added to the filtrate, and the mixture was stirred at 40 ° C. for 2 hours. The organic layer is separated, and the obtained organic layer is 2N hydrochloric acid,Wash sequentially with saturated aqueous sodium bicarbonate solution and water,It was dried over anhydrous magnesium sulfate. Remove the solvent under reduced pressure,Crude colorless liquid [H1] (244.5 g) was obtained. |
With dmap In dichloromethane at 0 - 20℃; | ||
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In Petroleum ether for 47h; Ambient temperature; | |
86% | With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 6h; | |
50% | With titanium tetrachloride In dichloromethane at 40℃; for 7h; Molecular sieve; | 2.3 Typical reaction conditions General procedure: A typical reaction was carried out in a 10 mL flask.Alcohol (5 mmol), 3,4-dihydro-2H-pyran (DHP,5.5 mmol), Ti4?/4A (0.5 g) and dichloromethane (3 mL)were stirred at 40 C for 7 h. The solid was filtered, andwashed with dichloromethane, then the filtrate was evaporated.The residue was subjected to GC-MS analysis andNMR spectroscopy. The crude product could be purified bycolumn chromatography (Kieselgel, hexane:acetone 4:1). |
87 % Chromat. | With trichloroisocyanuric acid at 60 - 80℃; for 7h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 30C2H3O2(1-)*72H2O*42H4N(1+)*72Mo(6+)*60Mo(5+)*372O(2-); oxygen In water at 25℃; for 5h; Green chemistry; chemoselective reaction; | |
95% | With tetra-n-butylammonium hydrogen monopersulfate In water at 70℃; for 0.25h; | |
94% | With tetra-n-butylammonium peroxomonosulfate; meso-tetraphenylporphyrin iron(III) chloride In water at 70℃; for 0.25h; Air; |
93% | With tetra-n-butylammonium peroxomonosulfate In water at 70℃; for 0.75h; | |
92% | With tetra-n-butylammonium hydrogen monopersulfate In water at 70℃; for 1.5h; chemoselective reaction; | |
90% | With tert.-butylhydroperoxide; C11H15MoNO5 In 1,2-dichloro-ethane at 80℃; for 0.75h; chemoselective reaction; | |
85% | With copper phthalocyanine; tetra-n-butylammonium hydrogen monopersulfate In water at 70℃; for 0.25h; chemoselective reaction; | |
79% | With tert.-butylhydroperoxide; vanadyl ethyl phosphonate silica In decane; acetonitrile at 80℃; for 24h; | |
76% | With (TBA)2[SeO4{WO(O2)2}2]; dihydrogen peroxide In water; acetonitrile at 59.84℃; for 4h; | |
71% | With 4-nitroperbenzoic acid In chloroform for 2h; Ambient temperature; | |
58% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at -78℃; for 4h; | |
38% | With α-molybdenum trioxide; dihydrogen peroxide In ethanol at 70℃; for 22h; Green chemistry; chemoselective reaction; | |
With oxygen; isobutyraldehyde In 1,2-dichloro-ethane for 14h; Ambient temperature; Yield given; | ||
92 % Chromat. | With oxygen; isobutyraldehyde In 1,2-dichloro-ethane at 25℃; for 4h; | |
33 % Turnov. | With sodium hydroxide; sodium tungstate; aluminium trichloride; dihydrogen peroxide; magnesium chloride In methanol Ambient temperature; | |
With dihydrogen peroxide; Aliquat 336; chloroacetic acid at 60℃; for 4h; | ||
Multi-step reaction with 2 steps 2: 92 percent / Amberlyst A 26 (OH- form) / methanol / 2 h / Ambient temperature | ||
With dihydrogen peroxide In water at 50℃; for 2h; | ||
With tert.-butylhydroperoxide; C15H14MoNO4 In 1,2-dichloro-ethane at 80℃; for 0.75h; chemoselective reaction; | ||
With tert.-butylhydroperoxide; C16H19MoNO5 In 1,2-dichloro-ethane at 80℃; for 0.416667h; chemoselective reaction; | ||
>99%Chromat. | With 3-Methylpyrazole; dihydrogen peroxide; methyltrioxorhenium(VII) In neat (no solvent) at 10℃; for 1.5h; | |
61 %Chromat. | With tert.-butylhydroperoxide In water at 60℃; for 8h; Green chemistry; chemoselective reaction; | |
With [Cu(1,10-phenanthroline)(4,4'-bipyridine)3(H2O)]2*[PW12O40]; dihydrogen peroxide In water; acetonitrile at 50℃; for 7h; chemoselective reaction; | ||
74 %Chromat. | With tetra-n-butylammonium hydrogen monopersulfate In water at 60℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With jones reagent In acetone at 0℃; for 1h; | |
76% | With Jones reagent In acetone at 0℃; for 1h; Inert atmosphere; | |
65% | With jones reagent In acetone at 0 - 20℃; |
58% | With Jones reagent In acetone at 0 - 20℃; for 8h; | 3-Methyl-3-butenoic Acid (9) To a stirred solution of 8 (6.0 g, 69.7 mmol) in acetone (200 mL) the Jones reagent (36.5 mL, 97.5 mmol) was dropwise added at 0 °C for 2 h, and the resulting mixture was stirred at room temperature for another 6 h. The reaction mixture was quenched with H2O (50 mL),and most of acetone was evaporated under reduced pressure. The residue was extracted with Et2O(3 × 20 mL), The combined ethereal solution was washed with saturated aqueous NaHCO3 solution.The combined aqueous layer was acidified with diluted hydrochloric acid (2 M) to pH = 3, and thenextracted again with Et2O (2 × 20 mL). All combined ethereal solution was washed successively bywater, brine and dried (anhydrous MgSO4), concentrated in vacuo. The residue was distilled to give 3.3 g (58%) of acid 9, colorless oil, b.p. = 86-88 °C (25 mmHg). 1H-NMR (300 MHz, CDCl3):δ = 10.14 (s, 1H, -COOH); 4.96 (dd, J = 1.5, 10.8 Hz, =CH2); 3.09 (s, 2H, -CH2-); 1.84 (s, 3H, -CH3). |
56% | With jones reagent In acetone for 5h; Ambient temperature; | |
56% | With Jones reagent In acetone at 0℃; for 1h; | |
16% | With Jones reagent In acetone at 0℃; for 1h; | 3-methylbut-3-enoic acid (1i) The 3-methylbut-3-enoic acid (1i) was synthesized using a reported procedure. 3 In a round bottom flask was placed a solution of 3-methylbut-3-en-1-ol (9.28 mmol, 1 equiv.) in acetone (46 mL, conc. = 0.2 mol/L). At 0°C, Jones' reagent (2.68 mol/L, 12.99 mmol, 1.4 equiv.) was added and the reaction mixture was stirred at 0°C for 1 h. The reaction mixture was washed with 2 M NaOH. Then the aqueous layer was acidified with HClccand extracted with Et2O (three times). The combined organic phases were dried over Na2SO4, filtrated, and the solvent was removed under vacuum. The residual oil was purified by distillation (bp 88-90°C (20 mmHg)). Colorless oil ; yield 162 mg (16%). |
With chromium(VI) oxide; sulfuric acid | ||
With chromium(VI) oxide; sulfuric acid; water In acetone at 0℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With bromine; sodium hydrogencarbonate In tetrachloromethane at 0℃; for 1h; | |
89% | With Oxone; ammonium bromide In water; acetonitrile for 4h; Reflux; | General procedure for the synthesis of dibromides: General procedure: To a solution of olefin (2 mmol) in CH3CN (10 mL) were added NH4Br (4.4 mmol) and Oxone (2.2 mmol) and the mixture was stirred at reflux temperature for the time shown in Table 2. After completion (as indicated by TLC), the reaction mixture was filtered and the solvent evaporated under reduced pressure. The products were purified by column chromatography (Hexane/EtOAc, 98:2) over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; for 4h; | |
84% | With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; for 3h; | |
Multistep reaction; |
With iodine; triethylamine; triphenylphosphine In dichloromethane at 0 - 22℃; | ||
Multi-step reaction with 2 steps 1: 85 percent / pyridine / 16 h / 0 °C 2: 72 percent / NaI / acetone / 2 h / Heating | ||
Multi-step reaction with 2 steps 1: 98 percent / Et3N / CH2Cl2 / 1.) 0 deg C, 1 h, 2.) r.t., 12 h 2: 96 percent / NaI / acetone / 24 h | ||
Multi-step reaction with 2 steps 1: 79 percent / pyridine / CH2Cl2 / 12 h / Ambient temperature 2: 40 percent / NaI / acetone / 10 h / Heating | ||
Multi-step reaction with 2 steps 1: 1) n-BuLi, / 1) THF, hexane, 0 deg C, 2) 25 deg C, 3h 2: 54 percent / NaI / acetone / 3 h / 25 °C | ||
Multi-step reaction with 2 steps 1: pyridine 2: NaI / dimethylformamide | ||
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane | ||
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0℃; | ||
Multi-step reaction with 2 steps 1: pyridine / 2.5 h / 0 °C 2: sodium iodide / acetone / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With magnesium(II) perchlorate at 20℃; for 0.5h; | |
96.7% | With toluene-4-sulfonic acid In toluene at 60 - 70℃; for 5h; | 2 Example 2: Preparation of 2-methyl-4-acetoxy-1-butene (III1) Into a 500 ml four-necked flask connected with a stirring, thermometer and reflux condenser, 300 g of n-hexane, 86.0 g (1.0 mol) of 2-methyl-4-hydroxy-1-butene (II), 112.0 g ( 1.1 mol) acetic anhydride, 0.4 g of p-toluenesulfonic acid, stirred at 65-70°C for 5 hours. Cooled to 40 to 45°C, changed to distillation system, first distilled to recover n-hexane, by-product acetic acid and excess acetic anhydride, then changed to high vacuum vacuum distillation (60-75°C/1-2mmHg) to obtain 123.8 g of 2-formaldehyde 4-acetoxy-1-butene (III1), the yield was 96.7%, and the gas phase purity was 99.6% |
94% | With pyridine for 18h; Ambient temperature; |
80% | With dmap for 1h; Ambient temperature; | |
75% | With pyridine; dmap at 20℃; for 8h; | |
41% | With pyridine; dmap at 20℃; Inert atmosphere; | |
With dmap; triethylamine In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 1H-imidazole In dichloromethane at 20℃; for 18h; | 1 Step 1: tert-butyl-dimethyl-(3-methylbut-3-enoxy)silane A mixture of 3-methylbut-3-en-1-ol (3.52 ml_, 34.83 mmol), te/f-butyldimethylsilyl chloride (6.3 g, 41.80 mmol) and Imidazole (4.75 g, 69.66 mmol) in DCM (113 mL ) was stirred at room temperature for 18 h. The reaction was quenched with aqueous NH4CI, the layers were separated and the aqueous layer was extracted with DCM. Purification by column chromatography (100g column, 1 to 10% EtOAc in cHex, 15 CV) gave the title compound (6.85 g, 98%, 34.18 mmol) as a colourless oil. 1 H NMR (Chloroform-d, 500 MHz): d 4.77 (1 H, s), 4.71 (1 H, s), 3.73 (2H, t, J 7.3 Hz), 2.26 (2H, t, J 7.3 Hz), 1.75 (3H, s), 0.91 (9H, s), 0.07 (6H, s). |
94% | With 1H-imidazole In dichloromethane at 20℃; for 18h; | |
90% | With 1H-imidazole In N,N-dimethyl-formamide for 4h; Ambient temperature; |
82% | With 1H-imidazole In dichloromethane at 20℃; | |
80% | Stage #1: 2-methyl-1-buten-4-ol With sodium hydride In tetrahydrofuran at 20℃; for 1h; Stage #2: tert-butyldimethylsilyl chloride In tetrahydrofuran at 20℃; for 1h; | |
68% | With 1H-imidazole In dichloromethane at 20℃; for 12h; | |
With 1H-imidazole In N,N-dimethyl-formamide for 0.5h; | ||
In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In diethyl ether at 0℃; for 1h; | |
100% | With triethylamine In dichloromethane at 0 - 20℃; | |
100% | With triethylamine In dichloromethane at 0 - 20℃; for 3h; |
100% | With triethylamine In dichloromethane at 5 - 20℃; for 4.33333h; | 373 Example 373: 4-methylpent-4-enenitrile. Mesyl chloride (22.0 mL, 284 mmol) was added dropwise to a solution of 3-methylbut-3- en-1-ol (20.0 g, 232.2 mmol) and triethylamine (50 mL, 358 mmol) in DCM (200 mL) at 5°C over 20 minutes, The reaction mixture was stirred at room temperature for 4 hours then poured into H2O (200 mL). The aqueous phase was collected and washed with DCM (50 mL). The combined organic phases were washed successively with 1M Hydrogen chloride (aq, 30 mL) and saturated NaHCO3 (aq, 30 mL) then dried over MgSO4, filtered and concentrated in vacuo to leave intermediate compound, 3-methylbut-3-enyl methanesulfonate (38.4 g, 100% yield). This intermediate was dissolved in DMSO (200 mL) and KCN (20.0 g, 307 mmol) was added and the reaction was stirred at 80°C for 16 hours. To the cooled reaction mixture was added H2O (300 mL) and the mixture was extracted with TBME (3 x 150 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo to leave the title compound as a brown oil. (19.2 g, 87% yield). 1H NMR (400 MHz, CDCl3) δ 4.94 - 4.85 (m, 1H), 4.85 - 4.74 (m, 1H), 2.48 (dd, J = 7.7, 6.6 Hz, 2H), 2.36 (t, J = 7.4 Hz, 2H), 1.77 (d, J = 1.4 Hz, 3H). |
99% | With triethylamine In dichloromethane at -5℃; for 0.5h; | |
99% | With triethylamine In dichloromethane at -5 - 25℃; for 0.583333h; | 68 Example 68 4-Mesyl-2-methylbutene (59) In a 250 ml flask, equipped with a magnetic stirrer and in a nitrogen atmosphere, 3-methylbut-3-enole (11.79 g, 137 mmol, 1 eq) dissolved in 100 ml of dichloromethane is added followed by triethylamine (20.81 g, 205.36 mmol, 1.5 eq) at -5° C. Mesyl chloride (17.25 g, 180.67 mmol, 1.1 eq) in solution in 20 ml of dichloromethane is then added over a 5 min period. After 30 min of reaction, the temperature is increased to 25° C. and the organic phase washed with iced water (100 ml), 10% hydrochloric acid (100 ml) and with a saturated NaHCO3 solution. After drying on sodium sulphate and evaporation of the dichloromethane, a colourless oil is obtained. Total formula: C6H12O3S Yield=99% Rf=0.5 (4:6 ethyl ether:petroleum ether). NMR 1H(CDCL3), δ(ppm): 1.8 (s, 3H, H-5); 2.48 (t, J3-4 6.7 Hz, 2H, H-3); 3.03 (s, 3H, H-6); 4.35 (t, 2H, H-4); 4.8 (s, 1H, H-1); 4.9 (s, 1H, H-1). |
91% | With triethylamine In dichloromethane at 0℃; for 0.25h; | |
88% | With triethylamine In dichloromethane at 0 - 20℃; for 3h; | 11.1 11.1 Synthesis of 3-Methylbut-3-en-1-yl methanesulfonate (91-2) 00218] To a solution of compound 91-1 (3.0 g, 34.88 mmol) and triethylamine (7.05 g, 69.76 mmol) in dichloromethane (30 ml) was added methanesulfonyl chloride (4.8 g, 41.86 mmol) at 0°C, then stirred at room temperature for 3 h. The mixture was quenched with water, two phases were separated. The dichloromethane layer was washed with water and brine, dried over anhydrous Na2S04. The solvent was removed under vacuum to give 5.0 g of compound 91-2 as a white solid (yield 88%). [00219] 1H NMR δΗ (400 MHz; CDCI3): 1.77 (s, 3H), 2.46 (t, J = 6.8 Hz, 2H), 3.00 (s, 3H), 4.33 (t, J = 6.8 Hz, 2H), 4.79 (s, 1 H), 4.87 (s, 1 H). |
With triethylamine In dichloromethane | ||
With triethylamine In diethyl ether for 0.25h; Ambient temperature; | ||
With triethylamine In dichloromethane at 0 - 20℃; for 1h; | ||
With triethylamine In dichloromethane at 0 - 20℃; for 15h; Inert atmosphere; | ||
With triethylamine In toluene at 5 - 20℃; | 1 In a 2 L four-necked round bottom flask equipped with a condenser, a thermometer, a dropping funnel and a mechanical stirrer, 172 g (2.00 mol) of isoprenol, 222 g (2.20 mol) of triethylamine and 800 g of toluene were placed. To this solution, while maintaining the internal temperature at 5 to 15° C., 240 g (2.10 mol) of methanesulfonyl chloride was added dropwise over 3 hours. After the completion of the dropwise addition, a reaction was carried out at 20° C. for 1 hour. To the obtained reaction solution, 400 g of water was added, and 703 g of an aqueous layer was then isolated to obtain 1127 g of an organic layer, i.e. a solution of methanesulfonic acid isoprenyl ester in toluene. | |
With triethylamine In dichloromethane at 0 - 23℃; for 0.5h; Inert atmosphere; | ||
With triethylamine In dichloromethane at 0℃; for 2h; | ||
With triethylamine In dichloromethane at 0℃; for 1.08h; | ||
With triethylamine In dichloromethane at 10 - 25℃; for 16h; Large scale; | 1.1 1. Preparation of 3-methylbut-3-en-1-yl methanesulfonate 3-methylbut-3-ene-1ol (1 kg, 11.61 mol) and triethylamine (1762 g, 17.42 mol) were added to the reaction vessel.Dichloromethane (10 L) was stirred and the temperature was lowered to 0 ° C, and methanesulfonyl chloride (1596 g, 13.92 mol) was added dropwise.The reaction temperature was controlled to be 10 ° C below, and after the completion of the addition, the temperature was naturally raised to 25 ° C for 16 hours, and the reaction was completed.Slowly add water (5L), stir for 20 minutes, let stand for stratification, discard the aqueous phase, and then use the saturated sodium bicarbonate aqueous solution in order.Wash with saturated aqueous sodium chloride solution, dry over anhydrous sodium sulfate, and filter.The solvent was evaporated under reduced pressure at 45 ° C to give crude title compound. | |
With triethylamine In dichloromethane at 0 - 20℃; for 1.08333h; | 14 5-methylhex-5-enoic acid and 2,2,2-trifluoroethyl 5-methylhex-5-enoate In a 500 mE round-bottomed flask equipped with a stir bar was added 3-methyl-3-buten-1-ol (11.7 mE, 116 mmol) in dry DCM (200 mE) to give a clear colorless solution. NEt3 (17.7 mE, 128 mmol) was added and the solution was cooled to 0° C. Methanesulfonyl chloride (9.96 mE, 128 mmol) was then added dropwise over 5 mm then stirred for 1 hat 0° C. The reaction mixture was diluted with DCM (200 mE), washed with 1M HC1 (200 mE), satd. NaHCO3 (250 mE) and brine (200 mE). The combined organic layer was dried over Na2SO4, filtered, and the solvent was removed under reduced pressure to give an orange-yellow oil that was used in the next step without thrther purification. | |
With dmap; triethylamine In dichloromethane at 0 - 23℃; for 16h; | ||
With triethylamine In dichloromethane at 0℃; for 1h; Inert atmosphere; | ||
With triethylamine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | ||
0.398 g | Stage #1: 2-methyl-1-buten-4-ol With triethylamine In dichloromethane at 0℃; Inert atmosphere; Stage #2: methanesulfonyl chloride In dichloromethane at 20℃; for 0.5h; | 25.1 Example 25: Preparation of TH-Z 534 step 1:3.15 mmol (0.27 g) of 3-methyl-3-buten-1-ol and anhydrous triethylamine (0.88 mL) were dissolved in 5 mL of anhydrous dichloromethane.The reaction was placed at 0 ° C and protected with nitrogen.Then 0.29 mL of methanesulfonyl chloride was slowly added dropwise to the reaction and stirred at room temperature for 30 min.The reaction is then filtered,Organic phase with 3N hydrochloric acid, saturated sodium bicarbonate and waterWash, dry with MgSO4, spin dry,Product A (2.43 mmol, 0.398 g) was obtained. |
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; | ||
With triethylamine In dichloromethane at 0 - 23℃; for 0.5h; Inert atmosphere; | ||
With triethylamine at 0 - 20℃; | ||
With triethylamine In dichloromethane at 0℃; for 3h; | 242A Example 242A: 3-methylbut-3-en-1-yl methanesulfonate To a solution of 3-methylbut-3-en-1-ol (23 g, 267 mmol) and triethylamine (74.4 mL, 534 mmol) in dichloromethane (300 mL) was added methanesulfonyl chloride (36.7 g, 320 mmol) dropwise at 0 °C. The reaction mixture was stirred at 0 °C for 3 hours. The mixture was transferred to a separatory funnel and washed with water (400 mL). The organic phase was dried over Na2SO4 and concentrated under reduced pressure to give the title compound (46 g, 266 mmol, yield 100%) which was used for next step directly. 1H NMR (400 MHz, CDCl3) δ ppm 4.89 (s, 1H), 4.81 (s, 1H), 4.34 (t, J = 6.84 Hz, 2H), 2.99-3.06 (m, 3H), 2.47 (t, J = 6.78 Hz, 2H), 1.79 (s, 3H). | |
With triethylamine In dichloromethane at 0 - 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With di-tert-butyl-diazodicarboxylate; triphenylphosphine In tetrahydrofuran at 70℃; | 29.a To a stirred solution of 3-methyl-3-buten-1-ol (1.17 ml) in tetrahydrofuran (30 ml) were added sequentially phenol (1.32 g), triphenylphosphine (3.85 g) and di-tert-butyl azodicarboxylate (3.27 g). The mixture was heated at 70° C. overnight and then was concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0->70:30) to give (3-methyl-but-3-enyloxy)-benzene (2.06 g, quant.) as a colourless semi-solid which crystallized on standing. |
91% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran; toluene for 1.5h; Inert atmosphere; Reflux; | |
79% | With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane for 3h; Ambient temperature; |
53% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 70℃; | |
52% | With di-tert-butyl-diazodicarboxylate; triphenylphosphine In tetrahydrofuran at 70℃; for 17h; | |
With dicyclohexyl-carbodiimide; copper chloride (I) 1.) 5h, 60 deg C, 2.) 12h, 100 deg C; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With diethyl diazodicarboxylate; triphenylphosphine In tetrahydrofuran; toluene at 20℃; for 1h; Heating / reflux; | |
99% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran for 4h; Heating; | |
98% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran |
98% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 12h; | |
95% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 3h; Heating; | |
94% | With di-isopropyl azodicarboxylate; triphenylphosphine | synthesis of 1-methoxy-4-(3-methylbut-3-enyloxy)benzene DIAD (6.3 mL, 32.5 mmol) was introduced with a syringe into an ice-cooled solution of 3-methyl-3-buten-1-ol (2 g, 23.2 mmol), PPh3 (8.55 g, 32.5 mmol) and 4-methoxyphenol (8.64 g, 69.6 mmol) in THF (100 mL). The reaction was then stirred at room temperature overnight. The solvent was evaporated and the residue was purified by chromatography on silica gel (petroleum ether/diethylether 90/10). The solvents were evaporated under reduced pressure to afford the product as a colorless oil (4.19 g, yield: 94%). 1H NMR (CDCl3): 1.80 (s, 3H), 2.48 (t, J = 6.9 Hz, 2H), 3.77 (s, 3H), 4.03 (t, J = 6.9 Hz, 2H), 4.80 (s, 1H), 4.84 (s, 1H), 6.79 - 6.88 (m, 4H). 13C NMR (CDCl3): 22.9, 37.4, 55.8, 67.2, 112.0, 114.6, 115.6, 142.4, 153.1, 153.8. |
93% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran Heating; | |
90% | With triphenylphosphine; diethylazodicarboxylate In dichloromethane at 0 - 20℃; for 24h; Inert atmosphere; | |
86% | With di-isopropyl azodicarboxylate; triphenylphosphine In dichloromethane for 3h; Ambient temperature; | |
84% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 3h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1H-imidazole In dichloromethane | |
99% | With 1H-imidazole In tetrahydrofuran for 1h; Ambient temperature; | |
99% | With dmap; triethylamine In dichloromethane at 0℃; for 12h; Inert atmosphere; |
98% | With 1H-imidazole In N,N-dimethyl-formamide for 6h; | 4.1.16. 4-tert-Butyldiphenylsilyloxy-2-methyl-1-butene To a stirred solution of 16 (200 mg, 2.33 mmol) in DMF (2 ml) were added imidazole (317 mg, 4.66 mmol) and tert-butyldiphenylchlorosilane (650 μl, 4.66 mmol). After stirring for 6 h, the mixture was poured into water. The aqueous layer was extracted with hexane, and the combined organic layer was washed with water and brine, and dried over MgSO4. After concentration in vacuo, the residue was purified by column chromatography with hexane to give the title compound (742 mg, 98%) as a colorless oil. [Found: C, 77.53; H, 8.07. C21H28OSi requires C, 77.72; H, 8.70%]; νmax (liquid film) 3071, 2930, 1651, 1472, 1428, 1111 cm-1; δH (400 MHz, CDCl3) 1.04 (s, 9H), 1.68 (s, 3H), 2.28 (t, J=6.9 Hz, 2H), 3.76 (t, J=6.9 Hz, 2H), 4.68 (s, 1H), 4.74 (s, 1H), 7.36-7.44 (m, 6H), 7.66-7.73 (m, 4H); δC (100 MHz, CDCl3) 19.2, 22.7, 26.8, 40.9, 62.8, 111.7, 127.6, 129.5, 134.0, 135.6, 143.0. |
With 1H-imidazole In dichloromethane at 25℃; for 10h; | 2.A; 6.A Step A Synthesis of Compound Int-6a To a mixture of 3-methylbut-3-en-l-ol (21 g, 244 mmol) and imidazole (33 g, 487 mmol) in DCM (200 mL) was added TBDPSC1 (100 g, 0.365 mmol) in portions. The mixture was stirred at 25°C for 10 hours before being washed with brine (100 mL). The aqueous layer was extracted with EtOAc (2 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography eluting with 100% PE to afford compound Int-6a. 'H NMR (400 MHz, CDCb) d: 7.68-7.66 (m, 4H); 7.42-7.36 (m, 6H); 4.74-4.67 (d, J = 24.8 Hz, 2H); 3.77-3.74 (t, J = 7.2 Hz, 2H); 2.29-2.25 (t, J = 6.8 Hz, 2H); 1.67 (s, 3H); 1.04 (s, 9H). | |
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium hydride In tetrahydrofuran at 20℃; for 12h; | |
91% | With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran 1.) r.t., 2.) 40 deg C, 4 h; | |
89% | With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran at 20℃; |
87% | With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran at 20℃; for 16h; | |
83% | Stage #1: 2-methyl-1-buten-4-ol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil at 0 - 20℃; | |
With sodium hydride In N,N-dimethyl-formamide at 20℃; Cooling with ice; | 11.1 Step 1: ((3-methylbut-3-enyloxy)methyl)benzene (1) BnBr was added to the mixture of alcohol and NaH in DMF cooled in an ice bath. The mixture was stirred at room temperature overnight and the solid was filtered. The solvent was removed and the residue was purified by column chromatography to give compound 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In dichloromethane at 0℃; for 0.666667h; | 55 Example 55 3-methylbut-3-enyl benzoate (47) In a 250 ml flask, in a nitrogen atmosphere, 3-methylbut-3-enole (10 g, 116 mmol, 1 eq) dissolved in 100 ml of dichloromethane is introduced, followed by triethylamine (23.5 g, 236 mmol, 2 eq) at -0° C. Benzoyl chloride (24.4 g, 174 mmol, 1.5 eq) in solution in 20 ml of dichloromethane is then added over a 10 min period. After 30 min of reaction, the temperature is increased to 25° C. and the organic phase washed with iced water (100 ml), 10% hydrochloric acid (100 ml) and with a saturated NaHCO3 solution. After drying on sodium sulphates and evaporation of the dichloromethane, the residual oil obtained undergoes silica gel chromatography (4:6 ethyl ether:petroleum ether) to produce a colourless oil. Total formula: C12H14O2 Yield=100% Rf=0.70 (4:6, ethyl ether:petroleum ether). NMR 1H(CDCL3), δ(ppm): 1.84 (S, 3H, H-5), 2.51 (t, J2-1 6.7 Hz, 2H, H-2), 4.47 (t, J1-2 6.7 Hz, 2H, H-1), 4.82-4.92 (m, 2H, H-4), 7.40-7.50 (m, 2H, H-ar), 7.52-7.65 (m, 1H, H-ar), 8.02-8.12 (m, 2H, H-ar). NMR 13C(CDCL3), δ(ppm): 22.96 (1C, C-5), 37.24 (1C, C-2), 63.59 (1C, C-1), 112.85 (1C, C-4), 128.76-129.80 (4C, C-ar), 130.82 (1C, C-C=O), 133.28 (1C, C-ar), 142.15 (1C, C-3), 166.99 (1C, C-carbonyl). MS FAB>0 m/z (NOBA): 191 [M+H]+; 212 [M+Na]+. |
99% | With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | |
99% | With dmap In dichloromethane at 0 - 20℃; Inert atmosphere; |
93% | With dmap; triethylamine In dichloromethane at 20℃; | |
93% | With dmap; triethylamine In dichloromethane at 0 - 20℃; | |
93% | With dmap; triethylamine In dichloromethane at 0 - 20℃; | Example Synthetic Procedure for the Synthesis of Esters 1a, 1 g, 1n General procedure: A 20-mL vial fitted with a stirring bar was charged with alcohol (2 mmol), Et3N (2 equiv) and dry DCM (10 mL). The mixture was cooled down to 0° C. and benzoyl chloride (1.2 equiv) and 5 mg DMAP were then added sequentially. The mixture was stirred overnight and then it was diluted with 50 mL DCM, washed with 1M aqueous HCl (2×20 mL), saturated NaHCO3 (20 mL) and brine (20 mL), sequentially. The organic layer was then dried with Na2SO4 and concentrated. The residue was purified with column chromatography to afford the desired esters 1a (yield: 93%), 1g (yield: 90%), 1n (yield: 95%). |
90% | With triethylamine In dichloromethane at 20℃; for 3.5h; | |
90% | With triethylamine In dichloromethane at 0 - 20℃; | |
86% | With triethylamine In dichloromethane at 0 - 20℃; for 3.83333h; | |
With pyridine | ||
With dmap; triethylamine In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.4% | With acetylacetonatodicarbonylrhodium(l); tris(2-tert-butyl-4-methylphenyl)phosphite; hydrogen; triethylamine In toluene at 80℃; for 6h; | 1 Reference Example 1 A toluene solution (175 mL) obtained by dissolving (acetylacetonato)di-carbonyl rhodium (36.1 mg, 0.14 mmol) and tri(2-tert-butyl-4-methylphenyl)phosphite (11.9 g, 22.8 mmol), and triethylamine (1.0 g) were added to 3-methyl-3-butene-1-ol (3,325 mL, 2,840 g), followed by heating at 80° C. Pressure in a reactor was maintained at 5 MPa with a mixed gas of carbon monoxide:hydrogen=1:1 (molar ratio), and reaction was conducted in an offgas flow rate of 20 L/hr. Conversion of 3-methyl-3-butene-1-ol reached 100% in 6 hours, and a reaction solution obtained was subjected to simple distillation to obtain 2-hydroxy-4-methyltetrahydropyrane having a purity of 96.3% (yield: 92.4%). |
92.4% | With acetylacetonatodicarbonylrhodium(l); tris(2,4-di-tert-butylphenyl)phosphite; hydrogen; triethylamine In toluene at 80℃; for 6h; | 1 <Refernce Example 1> Of 3-methyl-3-buten-1-ol (3325mL, 2840g), and then adding the rhodium dicarbonyl acetylacetonate (36.1mg, 0.14mmol) and tris (2-t-butyl-4-methylbenzene yl) phosphite (11.9g, 22.8mmol) in toluene (175mL), and triethylamine (1.0g) and heated to 80 , carbon monoxide: hydrogen = 1: 1 (molar ratio) gas mixture of the reaction the internal pressure was maintained at 5Mpa, to the exhaust gas flow rate 20L / hr to react. In 6 hours at 3-methyl-3-buten-1-ol conversion reaches 100%, the resulting reaction mixture by simple distillation, thereby obtaining 96.3% purity of 2-hydroxy-4-methyl-tetrahydro- pyran (yield 92.4%). |
92.4% | With dicarbonylacetylacetonato rhodium (I); tris(2-tert-butyl-4-methylphenyl)phosphite; hydrogen; triethylamine In tetrachloromethane; toluene at 80℃; for 6h; | 1 Reference Example 1 the case of3-Methyl-3-buten-1-ol(3325 mL, 2840 g, (acetylacetonato) dicarbonylrhodium (36.1 mg, 0.14 mmol)And tri (2-tert butyl-4-methylphenyl) phosphite(11.9 g, 22.8 mmol)Was dissolved in toluene (175 mL), And triethylamine (1.0 g) were added and the mixture was heated to 80 ° C., carbon monoxide: hydrogen = 1: 1(Molar ratio), the internal pressure of the reactor was maintained at 5 MPa,The reaction was carried out at an off-gas flow rate of 20 L / hr.The conversion rate of 3-methyl-3-buten-1-ol was 100% in 6 hours,By simple distillation of the resultant reaction solution, purity of 96.3%2-hydroxy-4-methyltetrahydropyran was obtained (yield: 92.4%). |
73% | With hydrogen In toluene at 80℃; for 24h; | |
With acetylacetonatodicarbonylrhodium(l); 4,8-bis(1,1-tert-butyl)-1,2,10,11-tetramethyl-N,N-bis(4-methylphenyl)[d,f][1,3,2]dioxaphospho-6-amine; diethylamine at 100℃; for 6h; Autoclave; Inert atmosphere; | 24 General procedure: In a nitrogen atmosphere0.35 mmol Rh (CO) 2acac and 1.75 mmol phosphine ligand L1 were independently dissolved in two different 1.75 moles of 3-methyl-3-buten-1-ol (IPEA, total molar amount of 3.5 mol) The molar concentration of the catalyst in the IPEA was 100 ppm in terms of rhodium and 5: 1 at the rhodium rhodium ratio.Before the feed, replace the inside of the autoclave with nitrogen for 3 times,0.07 mol of diethylamine (molar ratio of diethylamine to IPEA of 0.02: 1) was added,Rhodium metal compound solution,Phosphine ligand solution were added to the reactor, replaced with syngas 3 times,Stirring at atmospheric pressure for 1h, and then boost to 4MPa, heating to 100 , constant pressure for 5 hours.To the room temperature, pressure relief, remove the reaction solution, using Shimadzu GC-2010 gas chromatography analysis reaction composition,The results showed that the conversion of 3-methyl-3-buten-1-ol (IPEA) was 75.3%The selectivity of 2-hydroxy-4-methyltetrahydropyran (MHP) was 63.2% (based on the converted 3-methyl-3-buten-1-ol, the same below). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | Stage #1: 2-methyl-1-buten-4-ol With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In diethyl ether; toluene at 0 - 20℃; for 6h; Stage #2: ethyl bromide In diethyl ether; toluene at -78 - 20℃; | X1.ii Step (ii) of Example X1: 3-Methylenehexan-1-ol Butyllithium (a 2.66 M toluene solution) (82 ml, 218.2 mmol) was added to a solution of 39 ml (258 mmol) of N,N,N',N'-tetramethylethylenediamine in diethyl ether (148 ml), which had been cooled to 0°C, and the mixture was then stirred at room temperature for one hr. The reaction solution was cooled to 0°C. 3-Methyl-3-buten-1-ol 10.1 ml (99.2 mmol) was added to the cooled solution, and the mixture was then stirred at room temperature for 6 hr. The reaction solution was cooled to -78°C. A solution of 8.9 ml (119 mmol) of bromoethane in diethyl ether (29.2 ml) was added to the cooled solution. The mixture was gradually raised to room temperature and was stirred for 15 hr. A saturated aqueous ammonium chloride solution was added thereto, and the mixture was extracted with dithyl ether. The organic layer was washed with a 3% aqueous citric acid solution, a saturated aqueous sodium hydrogencarbonate solution, and saturated brine in that order, was dried over anhydrous magnesium sulfate, and was then filtered. The filtrate was concentrated under the reduced pressure, and the residue was then purified by distillation under the reduced pressure to give 1.4 g (yield 12%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 0.80 (3H, t, J = 7.3 Hz), 1.35 (2H, tq, J = 7.3. 7.5 Hz), 1.89 (2H, t, J = 7.5 Hz), 2.17 (2H, t, J = 6.3 Hz), 3.59 (2H, dt, J = 5.3, 6.1 Hz), 4.70 (1H, dd, J = 0.7, 1.2 Hz), 4.74 (1H, d, J = 1.5 Hz). MS (GC) m/z 114 [M]+. |
12% | Stage #1: 2-methyl-1-buten-4-ol With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In diethyl ether; toluene at 0 - 20℃; Stage #2: ethyl bromide In diethyl ether; toluene at -78 - 20℃; Stage #3: With water; ammonium chloride In diethyl ether; toluene | 16.ii Step (ii) of Example 16: 3-Methylenehexan-1-ol Butyllithium (a 2.66 M toluene solution) (82 ml, 218.2 mmol) was added to a solution of 39 ml (258 mmol) of N,N,N',N'-tetramethylethylenediamine in diethyl ether (148 ml), which had been cooled to 0°C, and the mixture was then stirred at room temperature for one hr. The reaction solution was cooled to 0°C. 3-Methyl-3-buten-1-ol 10.1 ml (99.2 mmol) was added to the cooled solution, and the mixture was then stirred at room temperature for 6 hr. The reaction solution was cooled to -78°C. A solution of 8.9 ml (119 mmol) of bromoethane in diethyl ether (29.2 ml) was added to the cooled solution. The mixture was gradually raised to room temperature and was stirred for 15 hr. A saturated aqueous ammonium chloride solution was added thereto, and the mixture was extracted with dithyl ether. The organic layer was washed with a 3% aqueous citric acid solution, a saturated aqueous sodium hydrogencarbonate solution, and saturated brine in that order, was dried over anhydrous magnesium sulfate, and was then filtered. The filtrate was concentrated under the reduced pressure, and the residue was then purified by distillation under the reduced pressure to give 1.4 g (yield 12%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 0.80 (3H, t, J = 7.3 Hz), 1.35 (2H, tq, J = 7.3. 7.5 Hz), 1.89 (2H, t, J = 7.5 Hz), 2.17 (2H, t, J = 6.3 Hz), 3.59 (2H, dt, J = 5.3, 6.1 Hz), 4.70 (1H, dd, J = 0,7, 1.2 Hz), 4.74 (1H, d, J = 1.5 Hz). MS (GC) m/z: 114 (M+). |
12% | Stage #1: 2-methyl-1-buten-4-ol With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In diethyl ether; toluene at 0 - 20℃; for 6h; Stage #2: ethyl bromide In diethyl ether; toluene at -78 - 20℃; for 15h; | 47.ii (ii) 3-Methylene hexan-1-ol Butyllithium (2.66 M toluene solution) (82 ml, 218.2 mmol) was added to a solution of 39 ml (258 mmol) of N,N,N',N'-tetramethylethylenediamine in diethyl ether (148 ml) which had been cooled to 0°C, and the mixture was stirred at room temperature for 1 hr. The reaction solution was cooled to 0°C, 10.1 ml (99.2 mmol) of 3-methyl-3-buten-1-ol was added thereto, and the mixture was stirred at room temperature for 6 hr. The reaction solution was cooled to -78°C, a solution of 8.9 ml (119 mmol) of bromoethane in diethyl ether (29.2 ml) was added to the cooled solution. The temperature of the mixture was gradually raised to room temperature before the mixture was stirred for 15 hr. A saturated aqueous ammonium chloride solution was added thereto, and the mixture was extracted with diethyl ether. The organic layer was washed with a 3% aqueous citric acid solution, a saturated aqueous sodium hydrogencarbonate solution, and saturated brine in that order, was dried over anhydrous magnesium sulfate, and was then filtered. The filtrate was concentrated under the reduced pressure, and the residue was then purified by distillation under the reduced pressure to give 1.4 g (yield 12%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 0.80 (3H, t, J = 7.3 Hz), 1.35 (2H, tq, J = 7.3. 7.5 Hz), 1.89 (2H, t, J = 7.5 Hz), 2.17 (2H, t, J = 6.3 Hz), 3.59 (2H, dt, J = 5.3, 6.1 Hz), 4.70 (1H, dd, J = 0.7, 1.2 Hz), 4.74 (1H, d, J = 1.5 Hz). MS (GC) m/z: 114 (M+). |
Stage #1: 2-methyl-1-buten-4-ol With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In diethyl ether; hexane at 20℃; for 6h; Stage #2: ethyl bromide In diethyl ether at -78 - 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With molecular sieve; pyridinium chlorochromate In dichloromethane at 20℃; for 4h; | |
51.1% | With oxygen In para-xylene at 130℃; for 6h; | 3 EXAMPLE 3Oxidation of Isoprenol to Prenal by the Process According to the InventionIn a round-bottom flask with a reflux condenser, the catalyst (510 mg, 1.5% by weight of Au/hydrotalcite) was added to a solution of isoprenol (550 mg, 6.4 mmol) in p-xylene (25 mL), and the reaction was blanketed with air at 130° C. and stirred for 6 h. Filtration of the catalyst gave 16.8 g of a yellowish liquid of the following composition: 1.63% by weight of prenal (3-methylbut-2-en-1-al, 3.27 mmol), 1.42% by weight of isoprenol (2.79 mmol), corresponding to 56.4% conversion, 88.1% selectivity and 51.1% yield. |
62.2 %Chromat. | With [Ru(PnOct3)4(H)2] In cyclohexanone at 120℃; for 20h; Reflux; Inert atmosphere; Schlenk technique; | I.b.1 I.b. Dehydrogenation of isoprenol I.b. Dehydrogenation of isoprenolI.b.1 A solution of isoprenol (1.0 g, 11.6 mmol) and [Ru(Pn-Oct3)4(H)2] (200 mg, 0.13 mmol) in 15 g cylohexanone was stirred at 120°C for 20 hours under inert conditions (argon atmosphere) in a Schlenk-flask (50 mL) equipped with a reflux condenser. After cooling to room temperature, the reaction mixture was analyzed by GC revealing the following percentage composition (based on the area percents of the respective peaks): prenol 0 %, prenal 62.2 %, 3-methyl-butan-1-ol 0 %, isoprenol 37.1 %, iso-valeraldehyde 0 %. |
Multi-step reaction with 2 steps 1: bis-μ-dichloro(1,5-cyclooctadiene)ruthenium(II); 1-butyl-3-methylimidazolium chloride; potassium <i>tert</i>-butylate; tricyclohexylphosphine / toluene / 12 h / Reflux; Inert atmosphere; Schlenk technique 2: [Ru(PnOct3)4(H)2] / 20 h / 120 °C / Reflux; Inert atmosphere; Schlenk technique | ||
62.2 %Chromat. | With [Ru(PnOct3)4(H)2] In cyclohexanone at 120℃; for 20h; Inert atmosphere; Schlenk technique; | I.b.1 I.b. Dehydrogenation of isoprenol I.b. Dehydrogenation of isoprenolI.b.1 A solution of isoprenol (1.0 g, 11.6 mmol) and [Ru(Pn-Oct3)4(H)2] (200 mg, 0.13 mmol) in 15 g cylohexanone was stirred at 120°C for 20 hours under inert conditions (argon atmosphere) in a Schlenk-flask (50 mL) equipped with a reflux condenser. After cooling to room temperature, the reaction mixture was analyzed by GC revealing the following percentage composition (based on the area percents of the respective peaks): prenol 0 %, prenal 62.2 %, 3-methyl-butan-1-ol 0 %, isoprenol 37.1 %, iso-valeraldehyde 0 %. |
Multi-step reaction with 2 steps 1: bis-μ-dichloro(1,5-cyclooctadiene)ruthenium(II); 1-butyl-3-methylimidazolium chloride; potassium <i>tert</i>-butylate; tricyclohexylphosphine / toluene / 12 h / Reflux; Inert atmosphere 2: [Ru(PnOct3)4(H)2] / 20 h / 120 °C / Inert atmosphere; Schlenk technique | ||
Multi-step reaction with 2 steps 1: 5%-palladium/activated carbon; oxygen / 5 h / 80 °C / 3750.38 Torr 2: oxygen; / 5 h / 60 °C / 15001.5 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; | |
90% | With calcium oxide In 2-methyltetrahydrofuran at 20℃; for 6h; Green chemistry; chemoselective reaction; | |
82% | With triethylamine In dichloromethane for 2h; |
45% | With 2,6-dimethylpyridine In diethyl ether at 20℃; | |
With triethylamine In dichloromethane at 20℃; for 14h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With phenyltrimethylammonium tribromide In acetonitrile at 28℃; for 12h; | |
64% | With trimethylphenylammonium tribromide In water; acetonitrile at 28℃; for 12h; | 4.1. General procedure for sharpless aziridination General procedure: To a mixture of an appropriate olefin (3 mmol) and TsNClNa*3H2O (CAT) (0.930 g, 3.3 mmol) in CH3CN (15 mL), was added phenyltrimethylammonium tribromide, (PTAB) (0.113 g, 0.3 mmol) at 28 °C. After 12 h of vigorous stirring, the reaction mixture was concentrated and filtered through a short column of silica gel and eluted with 10% EtOAc in hexanes. After evaporation of solvent, the resultant solid was purified by flash column chromatography to yield the corresponding aziridines in good yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium carbonate In 1-methyl-pyrrolidin-2-one at 140℃; for 24h; | |
80% | With sodium carbonate In 1-methyl-pyrrolidin-2-one at 80 - 150℃; for 12 - 24h; | 1.2; 1 3.42 g (20 mmol) of 4-bromotoluene was dissolved by adding 50 mL of l-methyl-2-pyrrolidinone (NMP) in a high-pressure reactor. 4.49 mg (0.02 mmol) of palladium diacetate, 4.24 g of sodium carbonate and 3.44 g (40 mmol) of 3-methyl-3-buten-l-ol were added to the solution. The reaction temperature was maintained at between 80 °C and 150 °C, and the reaction was performed for 12-24 hours.[49] After the termination of the reaction, the resulting mixture was subject to the separation of an organic layer using water and diethyl ether, followed by condensation of the organic layer. The desired product was obtained in a pure form using column chromatography or fractional distillation. The analysis of the product using H NMR (Figure 1) and gas chromatography shows that a pure aldehyde compound was produced as shown in Scheme 3 below. The amounts of the reactants, the kinds of the bases used and yields are presented in Table 1.[50] Scheme 3 [51] |
67% | With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one at 135℃; for 24h; | 1.3 After the termination of the reaction, the resulting mixture was subject to the separation of an organic layer using water and diethyl ether, followed by condensation of the organic layer. The desired product was obtained in a pure form using column chromatography or fractional distillation. The analysis of the product using H NMR (Figure 1) and gas chromatography shows that a pure aldehyde compound was produced as shown in Scheme 3 below. The amounts of the reactants, the kinds of the bases used and yields are presented in Table 1.[50] Scheme 3 [51] |
60% | With sodium acetate In 1-methyl-pyrrolidin-2-one at 135℃; for 24h; | 1.1 After the termination of the reaction, the resulting mixture was subject to the separation of an organic layer using water and diethyl ether, followed by condensation of the organic layer. The desired product was obtained in a pure form using column chromatography or fractional distillation. The analysis of the product using H NMR (Figure 1) and gas chromatography shows that a pure aldehyde compound was produced as shown in Scheme 3 below. The amounts of the reactants, the kinds of the bases used and yields are presented in Table 1.[50] Scheme 3 [51] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 7h; | |
64% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 14h; | G; H A solution of D-1 (100.0 mg, 0.37 mmol), 3-methyl-but-3-en-1-ol (32 mg, 0.37 mmol) and PPh3 (117 mg, 0.44 mmol) in THF (2 mL) was treated with DIAD (79 mg, 0.39 mmol). The reaction was stirred at room temperature for 14 h. Concentration and chromatograph on silica gel (20:1 hexane/EtOAc) gave 80 mg (64%) of F-7 as colorless oil. 1H NMR (300 MHz, CDCl3) δ7.30-7.10 (m, 7H), 6.82 (d, J=9.0 Hz, 2H), 4.82 (s, 1H), 4.78 (s, 1H), 4.49 (t, J=9.0 Hz, 1H), 4.08-3.99 (m, 2H), 3.01 (d, J=9.0 Hz, 2H), 2.47 (t, J=6.0 Hz, 2H), 1.78 (s, 3H), 1.11 (t, J=6.0 Hz, 3H); MS (ES) m/z: 361 (M+Na+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With triethylamine; tris-(o-tolyl)phosphine In acetonitrile at 80 - 81℃; for 24h; | 1-2 EXAMPLE 1-2Preparation of alkylated product from the mixture of 1-bromo-4-ethylbenzene and 3-methyl-3-buten-1-olTo a solution of 1.46 mmol (270 mg) of 4-bromoethylbenzene in 12 mL of acetonitrile, was added 0.073 mmol (16.4 mg) of palladium diacetate, 0.146 mmol (44.5 mg) of tri-ortho-tolylphosphine, 4.38 mmol (0.61 mL) of triethylamine and 1.46 mmol (0.147 mL) of 3-methyl-3-buten-1-ol. The mixture was refluxed at 80~81 DEG C. under ambient pressure for 24 hours. As illustrated in reaction formula II, the products were separated to the aldehyde and the mixture of the alkenes with column chromatography eluted with hexane and ethyl acetate (hexane:ethyl acetate=4:1). The yield is demonstrated in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With triethylamine; tris-(o-tolyl)phosphine;palladium diacetate; In acetonitrile; at 80 - 81℃; under 760.051 Torr; for 24h; | EXAMPLE 1-3Preparation of alkylated product from the mixture of <strong>[41492-05-1]1-bromo-4-butylbenzene</strong> and 3-methyl-3-buten-1-olTo a solution of 1.46 mmol (311 mg) of 4-bromobutylbenzene in 12 mL of acetonitrile, was added 0.073 mmol (16.4 mg) of palladium diacetate, 0.146 mmol (44.5 mg) of tri-ortho-tolylphosphine, 4.38 mmol (0.61 mL) of triethylamine and 1.46 mmol (0.147 mL) of 3-methyl-3-buten-1-ol. The mixture was refluxed at 80~81 DEG C. under ambient pressure for 24 hours. As illustrated in reaction formula II, the products were separated to the aldehyde and the mixture of the alkenes with column chromatography eluted with hexane and ethyl acetate (hexane:ethyl acetate=4:1). The yield is demonstrated in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With triphenylphosphine; paraformaldehyde In benzene | XII EXAMPLE XII (Invention) EXAMPLE XII (Invention) A 1 liter stainless steel autoclave was charged with 200 ml (176 g) of benzene, 16 g of 94.4% paraformaldehyde (0.503 mol), 0.5 g (1.9 mmol) of molybdenum hexacarbonyl, 0.5 g (1.9 mmol) of triphenylphosphine, and 295 g (5.268 mol) of isobutylene. The reaction mixture was heated at 200°C for 1 hour. The reactor was cooled, vented and the contents filtered. The filtrate was distilled into four fractions. GLC analysis of the fractions showed that 30.28 g (0.352 mol) of 3-methyl-3-buten-1-ol had been obtained for a yield of 70% based on the starting formaldehyde. GLC analysis also indicated that 0.97 g of the formate ester of the alkenol had also been obtained. |
59% | With paraformaldehyde In benzene | II EXAMPLE II (Invention) EXAMPLE II (Invention) A 1 liter autoclave was charged with 200 ml (176 g) of benzene, 16 g of 94.4% paraformaldehyde (0.503 mol), 0.5 g fluorided alumina (having about 25 weight percent fluoride), and 295 g (5.26 mol) of isobutylene. The reaction mixture was heated at 200°C for 1 hour while the pressure (autogeneous) ranged from 1,700 down to 1,450 psig. The reactor was cooled, vented and the contents filtered. The filtrate was fractionally distilled into three fractions. Analysis of the fractions by GLC indicated that 25.38 g (0.295 mol) of 3-methyl-3-buten-1-ol had been obtained for a yield of 59 percent based on the starting formaldehyde. |
50% | With paraformaldehyde In benzene | XX EXAMPLE XX (Invention) EXAMPLE XX (Invention) A 1 liter stainless steel autoclave was charged with 200 ml (176 g) of benzene, 16 g of 94.4% paraformaldehyde, 0.5 g of vanadium (III) acetylacetonate [V(AcAc)3 ], and 300 g (5.357 mol) of isobutylene. The mixture was heated at 200°C for 1 hour while the pressure (autogeneous) ranged from 1,700 down to 1,600 psig. The reactor was cooled, vented and the contents filtered. The filtrate was distilled into four fractions. Analysis of the fractions by GLC showed that 21.62 g (0.251 mol) of 3-methyl-3-buten-1-ol had been obtained for a yield of 50% based on the starting formaldehyde. |
49% | With paraformaldehyde In benzene | XVI EXAMPLE XVI (Invention) EXAMPLE XVI (Invention) A 1 liter stainless steel autoclave was charged with 200 ml (176 g) of benzene, 16 g of 94.4% paraformaldehyde (0.503 mol), 0.2 g of μ, μ'-dichlorotetranitrosyldiiron, [Fe(NO)2 Cl]2 and 282 g (5.036 mol) of isobutylene. The reaction mixture was heated at 200°C for 1 hour while the pressure (autogeneous) ranged from 1,350 down to 1,050 psig. The reactor was cooled, vented and the contents filtered. The filtrate was distilled into four fractions. GLC analysis of the fractions indicated that 21.18 g (0.246 mol) of 3-methyl-3-buten-1-ol had been obtained for a yield of 49% based on the starting formaldehyde. |
44% | With paraformaldehyde In benzene | XXII EXAMPLE XXII (Invention) EXAMPLE XXII (Invention) A 1 liter stainless steel autoclave was charged with 200 ml (176 g) of benzene, 22 g of 94.4% paraformaldehyde (0.692 mol), 0.5 g of tungstic oxide (WO3), and 298 g (5.321 mol) of isobutylene. The mixture was heated at 200°C for 1 hour while the autogeneous pressure ranged from 2,000 down to 1,300 psig. The reactor was cooled, vented and the contents filtered. The filtrate was distilled into four fractions. GLC analysis of the fractions showed that 26.35 g (0.304 mol) of 3-methyl-3-buten-1-ol had been obtained for a yield of 44% based on the starting formaldehyde. |
41% | With paraformaldehyde In benzene | X EXAMPLE X (Invention) EXAMPLE X (Invention) A 1 liter stainless steel autoclave was charged with 250 ml (220 g) of benzene, 16 g of 95.4% paraformaldehyde (0.509 mol), 0.5 g of molybdenum hexacarbonyl, Mo(CO)6, and 300 g (5.357 mol) of isobutylene. The reaction mixture was heated at 200°C for 1 hour while the pressure (autogeneous) ranged from 2,000 down to 1,350 psig. The reactor was cooled and vented and the contents distilled into four fractions. GLC analysis of the fractions showed that 17.99 g (0.209 mol) of 3-methyl-3-buten-1-ol had been obtained for a yield of 41% based on the starting formaldehyde. |
With paraformaldehyde In nitrogen; <i>tert</i>-butyl alcohol | 1 EXAMPLE 1 EXAMPLE 1 In a stainless steel autoclave having an inner volume of 300 ml, 9.0 g of paraformaldehyde of 95% purity, 0.22 g of sodium hydrogenphosphate as catalyst, and 60 ml of t-butanol were placed and the autoclave was closed. While cooling the autoclave with a dry ice and methanol mixture, the air in the autoclave was replaced by nitrogen and then 150 ml of isobutene was added thereto. Then the autoclave was brought to room temperature and no leak was found. Then the mixture was reacted with stirring at 200° C. for 4 hours. After the reaction, the autoclave was cooled and the contents were taken off. The reaction product was pale yellow and no substance having high boiling point was found. The reaction product was analyzed quantitatively by gas chromatography. Conversion of paraformaldehyde was determined by the sodium sulfite method. Conversion of paraformaldehyde was 98.9 mole%, and there were obtained 85.0 mole% of 3-methyl-3-butene-1-ol and 5.9 mole% of 3-methyl-2-butene-1-ol based on the paraform-aldehyde reacted. Total selectivities for the unsaturated alcohols were 90.9 mole% and no 4,4-dimethylmetadioxane was produced. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With lithium acetate; tetrabutyl-ammonium chloride; palladium diacetate; lithium chloride In N,N-dimethyl-formamide at 70℃; for 72h; Inert atmosphere; | |
46% | Stage #1: 2-methyl-1-buten-4-ol; 1,4-bromoiodobenzene With lithium acetate; tetrabutyl-ammonium chloride; lithium chloride In N,N-dimethyl-formamide at 70℃; for 96h; Stage #2: With water; ammonium chloride In N,N-dimethyl-formamide | 58.a a) 4-(4-Bromophenyl)-3-methyl-butyraldehyde4-bromo-l-iodobenzene (2.5g, 8.84 mmol), lithium acetate (1.46g, 22.1 mmol), lithium chloride (375mg, 8.8 mmol), 3-methyl-3-buten-l-ol (761mg, 8.8 mmol), tetrabutylammonium chloride hydrate (4.91g, 17.7 mmol) and palladium(II)acetate (119mg, 4.9 mmol) were stirred for 4 days in dimethyl formamide (17 mL) at 7O0C. The reaction mixture was cooled and quenched with saturated ammonium chloride solution and extracted with diethylether (2 x 200 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (gradient of 0 to 10% ethylacetate in petroleum ether as eluent) to afford the carboxyaldehyde (975mg, 46%). 1H NMR (d6DMSO) δ (ppm): 0.93 (d, 3H); 2.20-2.60 (m, 5H); 7.01 (d, 2H); 7.39 (d, 2H); 9.70 (s, IH). |
With lithium acetate; tetrabutyl-ammonium chloride; palladium diacetate; lithium chloride In N,N-dimethyl-formamide at 70℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: 2-methyl-1-buten-4-ol With 2,2'-azobis(isobutyronitrile); oxygen In acetonitrile at 0℃; Stage #2: p-Chlorothiophenol With oxygen In acetonitrile at 0℃; for 4.5 - 6.5h; UV-irradiation; Stage #3: cyclohexanone In dichloromethane; acetonitrile at -10 - 20℃; | A 2-necked 500 ml round bottom flask was charged with a solution of 3-phenyl-3-propen-ol (1 g, 7.5 mmol) and AIBN (77.5 mg, 4.72 mmol) in acetonitrile (115 ml). The reaction vessel was flushed with oxygen for several minutes at 0° C. then stopped and kept under a positive pressure of pure oxygen, with the aid of two big oxygen balloons. The reaction mixture was vigorously stirred and UV irradiated at 0° C. using an externally mounted 100W BLACK-RAY UV lamp at a distance of 5-7 cm, with the simultaneous addition of 4-chlorothiophenol (1250 mg, 8.64 mol) solution in acetonitrile (32 ml) over a period of 30 min. After completion of the addition, the reaction was left to continue stirring at 0° C., for 4-6 hours or until consumption of starting materials (monitored by tlc). The reaction vessel was then cooled to -10° C., flushed with nitrogen and a solution of cyclohexanone (1703 mg, 17.35 mmol) in dichloromethane (32 ml) was added followed by catalytic amount of tosic acid. The mixture was left stirring at -10° C., and allowed to cool slowly to room temperature overnight. The solvent was removed by the rotary evaporator and Column Chromatography on the crude mixture gave an oily product in 72%. 1HNMR (400 MHz, CDCl3) δH 1.25, (s, 3H, CH3), 1.3-2.52 (m, 12H, CH2), 3.25 (dd, 1H, SCH2), 3.5 (d, 1H, SCH2), 3.75 (t, 2H, OCH2), 7.25 (d, 2H, Ar), 7.35 (d, 2H, Ar); 13CNMR (400 MHz, CDCl3), 136.23, 132.48, 131.50, 129.34, 106.83, 84.00, 58.91, 44.22, 42.02, 33.61, 25.81, 24.05, 23.43, 23.37, 22.97, 22.78.MS (ES+) m/z 342.8807, [M+Na]+ (100) 365.1/367.1, [2M+Na]+707.2/709.2, HRMS m/z calculated for C17H23NO3NaSCl 365.0954, found, 365.0940 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triphenylphosphine; diethylazodicarboxylate In dichloromethane; toluene at 0℃; for 3h; Inert atmosphere; | |
80% | With triphenylphosphine; diethylazodicarboxylate In dichloromethane at 0 - 20℃; | |
70% | With triphenylphosphine; diethylazodicarboxylate In dichloromethane at 0℃; for 4h; Inert atmosphere; |
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; for 24h; Inert atmosphere; Schlenk technique; | ||
With triphenylphosphine; diethylazodicarboxylate In dichloromethane at 0℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48.5% | With toluene-4-sulfonic acid In water; toluene at 110 - 120℃; Dean-Stark; | 1 A 0.75 L reactor equipped with a Dean-Stark-trap and a vacuum pump was charged with toluene (239 g) and p-toluene sulfonic acid (560 mg of a 65% solution in water, 2.11 mmol) and the solution was brought to 110 °C (ambient pressure). To this solution a mixture of 95.7 g(1.14 mol) prenal and 97.7 g(1.13 mol) of isoprenol was added by means of a syringe pump (0.7 mL/min). During the addition, water started to form and was removed into the Dean-Stark-trap. The heating temperature was kept at 120°C. At the end of the addition (i. e. after approximately 6 h) the temperature of the reactionmixture was 98°C. The reaction was heated for further 4 h after completion of the addition. After cooling to room temperature, 350 g of the reaction mixture (total mass of the mixture: 390 g) was distilled (bulb to bulb). The distillate (319 g) was analysed by GC. The yield of dehydro rose oxide (DHRO) was 48.5%, and the DHRO/NO ratio was 3.11 (in other words: 3.11:1). The reaction was carried out analogously with the catalysts listed in the below table. |
In water; toluene at 110 - 115℃; for 21.5h; | 1 EXAMPLE 1; In a reaction vessel with a volume of 5 l and provided with stirrer, water separator, condenser and a metering pump, 2000 g of toluene and 1.5 g of NaHSO4 (as 10% strength aqueous solution) were initially introduced and 7.67 mol (660 g) of 3-methylbut-3-en-1-ol and 7.67 mol (643.5 g) of 3-methylbut-2-en-1-al were metered in over the course of 16 h at 110 to 115° C. The water was continuously removed azeotropically from the reaction mixture with toluene and the toluene was returned. The reaction mixture was then stirred for a further 5.5 h at 115° C. The resulting reaction mixture was then washed with 278 g of 2% strength NaOH solution. The toluene was distilled off at a pressure of 200 mbar over a 30 cm-long column, filled with Raschig rings. The conversion to the dehydrorose oxide (DHR) was 62.7% of theory. Finally the DHR was separated from nerol oxide and high-boiling secondary components by distillation and obtained with a purity of >99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With triphenylphosphine; diethylazodicarboxylate In benzene | 3 N-[3-(3-Methyl-but-3-enyloxy)-phenyl]acetamide N-[3-(3-Methyl-but-3-enyloxy)-phenyl]acetamide A suspension of the mixture of N-(3-hydroxy-phenyl)-acetamide and acetic acid 3-formylamino-phenyl ester (18.12 g, 0.12 mol), 3-methyl-but-3-en-1-ol (8.6 g, 0.1 mol), DEAD (87 g, 0.2 mol) and Ph3P (31.44 g, 0.12 mol) in benzene (250 mL) was heated at reflux overnight and then cooled to room temperature. The reaction mixture was poured into water and the organic layer was separated. The aqueous phase was extracted with EtOAc (300*3 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography to give N-[3-(3-methyl-but-3-enyloxy)-phenyl]-acetamide (11 g, 52%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 84% 2: 9% | With Oxone; ammonium bromide In water; acetonitrile at 20℃; for 0.0166667h; regioselective reaction; | General procedure for the synthesis of bromohydrins: General procedure: To a solution of olefin (2 mmol) in CH3CN/H2O (1:1) (10 mL) were added NH4Br (2.2 mmol) and Oxone (2.2 mmol) and the mixture was stirred at room temperature for the time shown in Table 2. After completion (as indicated by TLC), the reaction mixture was filtered and the solvent evaporated under reduced pressure. The products were purified by column chromatography (Hexane/EtOAc, 90:10) over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; | |
93% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; | |
84% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; Inert atmosphere; |
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: 2-methyl-1-buten-4-ol With sodium hydride In tetrahydrofuran at 0 - 20℃; for 3h; Stage #2: 1,3,5-trichloro-2,4,6-triazine In tetrahydrofuran at 0 - 20℃; | 3 Example 3 To 16.6 g of sodium hydride (purity: 60% or more), 600 mL of tetrahydrofuran was added and the resultant reaction mixture was cooled down to 0°C, followed by dropping 34.5 g of 3-methyl-3-buten-1-ol into the reaction mixture at 4°C or less to be added. After the completion of the dropping, the resultant reaction mixture was stirred at room temperature for 3 hours. Then, the reaction mixture was cooled down again to 0°C and into the reaction mixture, 18.5 g of 2,4,6-trichloro-1,3,5-triazine dissolved in 110 mL of tetrahydrofuran was slowly dropped at 15°C or less to be added. At room temperature, the reaction was effected over one night and to the reaction mixture, water was added, followed by extracting the resultant reaction mixture with ethyl acetate. The extract was washed with water and was dried over anhydrous sodium sulfate and from the extract, the solvent was distilled off to obtain 31.1 g of a crude product. The crude product was recrystallized (ethyl acetate: hexane - 1:10) and the filtrate was purified with a column (ethyl acetate: hexane = 1:4) to obtain 26.1 g of 2,4,6-tri(3-which is the objective substance as a while solid. Yield: 76%, Purity: 97.0% (GC) To 25.4 g of 2,4,6-tri(3-methyl-3-butene-1-oxy)-1,3,5-triazine, 340 mL of chloroform was added and the resultant reaction mixture was cooled down to 0°C. To the reaction mixture, 61.6 g of methachloroperbenzoic acid (purity: about 77%) was added and while elevating gradually the temperature of the resultant reaction mixture from 0°C to room temperature, the reaction was effected over one night. To the reaction mixture, a 10% sodium thiosulfate aqueous solution was added and the resultant reaction mixture was extracted. The extract was washed with a sodium bicarbonate aqueous solution twice, was washed with water, and was dried over anhydrous sodium sulfate and from the extract, the solvent was distilled off to obtain 22.4 g of a crude product. The crude product was purified by recrystallization (ethyl acetate: hexane = 3:1) to obtain 18.3 g of 2,4,6-tri(3-methyl-3,4-epoxybutyl-1-oxy)-1,3,5-triazine (corresponding to Formula (1-6)) which is the objective substance as a white solid. Yield: 63%, Purity: 100% (GC) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triphenylphosphine; diethylazodicarboxylate In dichloromethane at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 60℃; | 3 General procedure A: Mitsunobu reaction General procedure: To a 50 mL flamed-dried flask equipped with a stir bar and a rubber septum were added phenol derivatives (6 mmol, 1 equiv), PPh3 (6.6 mmol, 1.1 equiv), corresponding alcohols (6.6 mmol, 1.1 equiv), and THF (20 mL). With stirring, DIAD (6.6 mmol, 1.1 equiv) was added dropwise. Upon completion, the reaction was heated to 60 °C overnight. The reaction mixture was then concentrated under vacuum and directly purified via flash chromatography on silica gel to afford the following compounds. 4.2.3 1-Chloro-3-((3-methylbut-3-en-1-yl)oxy)benzene (6o) Compound 6o was obtained in 96% yield as colorless oil (1.90 g) from 3-chlorophenol and 3-methyl-3-buten-1-ol, Rf=0.3 (Hexane); 1H NMR (400 MHz, CDCl3) δ 7.20-7.14 (m, 1H), 6.93-6.87 (m, 2H), 6.80-6.75 (m, 1H), 4.85-4.82 (m, 1H), 4.81-4.76 (m, 1H), 4.04 (t, J=6.8 Hz, 2H), 2.48 (t, J=6.8 Hz, 2H), 1.79 (d, J=0.9 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 159.6 (s), 141.9 (s), 134.8 (s), 130.1 (s), 120.8 (s), 114.9 (s), 113.1 (s), 112.1 (s), 66.6 (s), 37.0 (s), 22.8 (s). IR: ν 3077, 2936, 1651, 1679, 1470, 1428, 1387, 1263, 1231, 1071, 1042, 864, 840, 764 cm-1. HRMS calcd for C11H13ClO [M]: 196.0655, found: 196.0656. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris(2,2'-bipyridyl)ruthenium dichloride; Bromotrichloromethane; sodium L-ascorbate In methanol at 20℃; for 3h; Inert atmosphere; Irradiation; regioselective reaction; | 6 General procedure for photoredox-initiated thiol-ene click (TEC) reactions General procedure: A 5mL round-bottom flask equipped with a magnetic stir bar and rubber septum was charged with the starting olefin (1mmol, 1.0 equiv) and thiol (3.0mmol, 3 equiv) coupling partners, and sodium ascorbate (0.03mmol, 3mol%). The reaction components were dissolved in MeOH (0.4M). The metal complex Ru(bpy)3Cl2 (0.01mmol, 1mol%) was finally added, and the resultant mixture was degassed by sparging with argon for 15min in the dark. Finally, while stirring at room temperature under an argon atmosphere, BrCCl3 (0.05mmol, 5mol%) was added and the reaction vessel was surrounded by blue LEDs (2W). Powering on of this light source signified reaction commencement. Reactions were typically run for 3h, at, which point the LEDs were powered off and the MeOH removed by rotary evaporation. The reaction mixture was then dissolved in a 7:3 hexanes/ethyl acetate mixture and filtered through a plug of Celite. The crude filtrate was concentrated in vacuo and purified by flash chromatography over SiO2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With triisopropoxytitanium(IV) chloride; isopropylmagnesium bromide In diethyl ether at 35℃; for 1.5h; Inert atmosphere; diastereoselective reaction; | cyclopropanol 3a General procedure: A solution of a homoallylic alcohol (1 mmol), an ester (2 equiv),and chlorotitanium(IV) isopropoxide (1 equiv.) in Et2O (3 mL) was heated at gentle refluxunder argon. A solution of isopropyl magnesium bromide (2M in Et2O) was then addedover a period of 1 h. The resulting mixture was heated at reflux for an additional 30 minand then treated with H20 (0.5 mL) at 0 °C. The mixture was stirred for 30 min,inorganic precipitates were filtered through a pad of Celite, and the filter cake waswashed thoroughly with Et2O. The combined organic filtrates were dried over Na2SO4,and the solvent was removed under reduced pressure. Purification of the concentrateby silica gel chromatography (EtOAc/hexane) gave the cyclopropanol product as acolorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With triisopropoxytitanium(IV) chloride; isopropylmagnesium bromide In diethyl ether at 35℃; for 1.5h; Inert atmosphere; diastereoselective reaction; | cyclopropanol General procedure: A solution of a homoallylic alcohol (1 mmol), an ester (2 equiv),and chlorotitanium(IV) isopropoxide (1 equiv.) in Et2O (3 mL) was heated at gentle refluxunder argon. A solution of isopropyl magnesium bromide (2M in Et2O) was then addedover a period of 1 h. The resulting mixture was heated at reflux for an additional 30 minand then treated with H20 (0.5 mL) at 0 °C. The mixture was stirred for 30 min,inorganic precipitates were filtered through a pad of Celite, and the filter cake waswashed thoroughly with Et2O. The combined organic filtrates were dried over Na2SO4,and the solvent was removed under reduced pressure. Purification of the concentrateby silica gel chromatography (EtOAc/hexane) gave the cyclopropanol product as acolorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With triisopropoxytitanium(IV) chloride; isopropylmagnesium bromide In diethyl ether at 35℃; for 1.5h; Inert atmosphere; diastereoselective reaction; | cyclopropanol General procedure: A solution of a homoallylic alcohol (1 mmol), an ester (2 equiv),and chlorotitanium(IV) isopropoxide (1 equiv.) in Et2O (3 mL) was heated at gentle refluxunder argon. A solution of isopropyl magnesium bromide (2M in Et2O) was then addedover a period of 1 h. The resulting mixture was heated at reflux for an additional 30 minand then treated with H20 (0.5 mL) at 0 °C. The mixture was stirred for 30 min,inorganic precipitates were filtered through a pad of Celite, and the filter cake waswashed thoroughly with Et2O. The combined organic filtrates were dried over Na2SO4,and the solvent was removed under reduced pressure. Purification of the concentrateby silica gel chromatography (EtOAc/hexane) gave the cyclopropanol product as acolorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | General procedure 1 for Mitsunobu reactions with tetronic acids. General procedure: The tetronic acid (10.0 mmol) was dissolved in THF (100 ml) followed by addition of the primary alcohol(11.0 mmol). The mixture was cooled to 0 °C, triphenylphosphine (11.0 mmol) or tris(chlorophenyl)phosphine (11.0 mmol) were added and di-iso-propyl azodicarboxylate (11.0 mmol) or di-ethyl azodicarboxylate (11.0 mmol) were slowly dropped into the solution.The mixture was allowed to warm up to ambient temperature overnight. The solvent was removed under reduced pressure, and the residue was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With sodium carbonate In water; acetonitrile at 50℃; for 0.25h; | Synthesis via direct addition of ice sphere To a vigorously stirred solution of the 3-methyl-3-buten-1-ol (2) (1.21 mL, 12.0 mmol) and Na2CO3 (477 mg, 4.50 mmol) in acetonitrile/water (1:1, 5 mL) in a 50 ml wide-neck (NS 29/32) round-bottom flask at 50 °C was added a frozen ice sphere (-84 °C, 3.0 h freezing time) of 4-chlorophenyldiazonium chloride (1) (2.5 mL, 0.4 M, 1.00 mmol) (see preparation 4.2.1.1). After the melting process (ca. 25 s), the reaction mixture was stirred for a further 15 min at 50 °C. Afterwards, the reaction mixture was diluted with water (10 mL) and extracted with MTBE (3 * 30 mL). The combined organic layers were washed with brine (30 mL) and dried over Na2SO4. The solvents were removed under reduced pressure. The yield was determined by 1H NMR using dimethyl terephthalate as internal standard (55%). Then the product was purified by column chromatography on silica gel (hexane/EtOAc = 4:1) and gave 3 (97.9 mg, 0.29 mmol, 57%) as orange oil. |
52 %Spectr. | With water; sodium carbonate In acetonitrile at 50℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | Stage #1: 2-methyl-1-buten-4-ol; p-nitrobenzotrifluoride With [FeCl(((CH3)2C6H2(O)CH2)2NCH2C4H7O)]; phenylsilane In ethanol at 20℃; for 2h; Stage #2: With hydrogenchloride; zinc In ethanol; water at 60℃; for 1h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide In dichloromethane; water at 20℃; for 3h; Inert atmosphere; | (4S,5S)-6-bromo-2,2-dimethyl-4-(3-((3-methylbut-3-en-1-yl)oxy)prop-1-yn-1-yl)-1,3-dioxaspiro[4.5]dec-6-ene 5e 3-methylbut-3-en-1-ol (70 mg, 0.81 mmol, 3.0 eq.) was added to a solution of compound 131 (100mg, 0.27 mmol, 1.0 eq.) in CH2Cl2 (0.21 M). nBu4NHSO4 (0.027 mmol, 0.1 eq.) and a 50 % aqueous solution of NaOH (0.32 M) were added to the reaction mixture successively. After stirringthe reaction mixture at room temperature for 3 h, it was extracted with CH2Cl2. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified on silica gel to afford 5e in 89% (90 mg, 0.24 mmol) yield as colorless liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.6% | With sulfate modified MoO3/TiO2 In 5,5-dimethyl-1,3-cyclohexadiene at 47℃; for 5h; | 1 Preparation of phenyl-dihydropyran A column reactor equipped with 3 trays was charged with 255.0 g of benzaldehyde, 100.0 g of xylene and 0.8 g of SO42lto03 / Ti02. The reaction system was evacuated to -0.098 MPa and the material was heated to reflux 86.0 g of 3-methyl-3-butenol was added and the by-product water was transferred at a reflux temperature of 47 ° C and a reaction time of 5 h.The reaction is stopped by the addition of 3-methyl-3-butenol to 0.5% or less, the temperature is reduced to 30 to 50 ° C, filtered and then washed with water. The water layer is removed by static separation, the organic layer is distilled, Toluene and benzene with a purity greater than 96.5%Yl-dihydropyran, the yield was 82.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.4% | With β-zeolite In water at 50℃; for 30h; | 2 Example 1 Continuous system (circulation type), ethanol use As shown in FIG. 1, 100 mL of a strongly acidic ion exchange resin "Diaion PK 212LH" (manufactured by Mitsubishi Chemical Corporation) was filled in a jacketed tubular reactor (Hereinafter referred to as solid acid layer A), another jacketed tubular reactor was filled with 100 mL of molecular sieve 3A (hereinafter referred to as dehydrating agent layer), and both were connected. Warm water (heat medium) of 50 ° C was made to flow in a jacket of a tubular reactor filled with a strongly acidic ion exchange resin and cooling water (about 10 ° C) was supplied to the jacket of the tubular reactor filled with the molecular sieve 3A Refrigerant) flowed. Next, a mixed solution [ethanol / IPEA = 10 (mol)] of 460 g (9.99 mol) of ethanol dehydrated beforehand using Molecular Sieves 3A and 86 g (0.998 mol) of 3-methyl-3-butene-1ol Is passed through the solid acid layer A and then the dehydrating agent layer in the order of LHSV 30 hr , and the whole amount of the reaction mixture obtained is returned to the solid acid layer A again using a pump The reaction was carried out while circulating in the dehydrating agent layer at LHSV of 30 hr . The reaction mixture after reacting for 10 hours was analyzed by gas chromatography to find that the conversion rate of IPEA was 91.1% and the yield of 3-ethoxy-3-methyl-1-butanol was 62.9% It was. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 24℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: nicotinic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 1h; Stage #2: 2-methyl-1-buten-4-ol In dichloromethane at 20℃; | |
37% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; | |
37% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; | Example Synthetic Procedure for the Preparation of Ester 1h A 50-mL flask fitted with a stirring bar was charged with a solution of alcohol (2 mmol), EDCI (1.2 equiv), triethylamine (1.5 equiv), and DMAP (0.1 equiv) in dichloromethane (10 mL). Nicotinic acid (1 equiv) was then added at 0° C. and the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the resulting mixture was diluted with DCM (50 mL), washed by 1 N HCl (2×20 mL), 1 N aqueous NaHCO3 (2×20 mL), and brine (1×20 mL). The organic layer was dried (Na2SO4) and evaporated in vacuo. The resulting residue was purified by column chromatography to afford the desired ester 1h (yield: 37%). |
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With benzyltrimethylammonium chloride; sodium hydroxide In water at 40℃; for 4.5h; Inert atmosphere; | 1.1 (Step 1) Synthesis of 3-methyl-3-butenyl glycidyl ether A stirrer, a thermometer,In a 1 L reactor equipped with a dropping funnel, under a nitrogen stream,280 g (3.5 mol) of a 50% sodium hydroxide aqueous solution,200 g (2.32 mol) of 3-methyl-3-buten-1-ol,4.4 g (0.024 mol) of benzyltrimethylammonium chloride was charged and heated to 40 ° C.430 g (4.65 mol) of epichlorohydrin was added dropwise over 30 minutes,Followed by stirring at 40 ° C. for 4 hours.400 g of distilled water was added to the reaction solution to give an organicThe layers and aqueous layer were separated. After washing the organic layer with 400 g of distilled water,The mixture was concentrated under reduced pressure and the residue was further distilled under reduced pressure,175.2 g of 3-methyl-3-butenyl glycidyl ether(1.23 mol; yield 53%). |
81 g | With tetramethlyammonium chloride; sodium hydroxide at 50℃; for 2h; | <Synthetic Example of Compound Represented by General Formula (1)> In a 500 mL four-necked flask equipped with a stirring blade, a thermometer, and a cooling tube,129.2 g of isoprenol, 277.6 g of epichlorohydrin,1.7 g of tetramethylammonium chloride was charged,While maintaining the internal temperature at 50 ° C., 60.0 g of 48% NaOH was added dropwise,And the mixture was reacted with stirring for 2 hours. After the reaction, salts formed are removed,Epichlorohydrin and water were removed from the remaining organic layer,Intermediate (A) (in the above general formula (1), R 2 is a CH 2 CH 2 group,81 g of a compound having a structure in which R 3 is a CH 3 group). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With lithium hexafluorophosphate at 0℃; for 8h; Irradiation; Inert atmosphere; | 1-6; 1 In an oxygen-free and anhydrous atmosphere, 258.6g of tetrahydrofuran and 86.2g (1.0mol) of 3-methyl-3-butenol were added to the photochemical reactor, and then an inert gas was introduced into the reactor, and 75.96mg ( 0.5mmol) lithium hexafluorophosphate (0.05mol% relative to 3-methyl-3-butenol), start stirring until the solution is clear and transparent, then keep the temperature at 0°C, turn on the mercury lamp in the reactor, and control the wavelength to 650nm, Irradiated with a power of 350W for 8h, the conversion rate was determined to be 97% by calibration GC analysis, the selectivity of 3-methyl-2-butenol was 99.9%, and the formation of isoamyl alcohol was not detected. |
53.05% | With palladium 10% on activated carbon; oxygen at 80℃; for 5h; | I.6 I) Catalytic Isomerization The individual experiments were generally conducted under oxygenous atmosphere in a pressure-stable reactor with a mechanical stirrer. Performance of the catalytic isomerization on a laboratory scale was accomplished using a 350 mL glass pressure vessel (DN 50 for 8 bar), equipped with a baffle, a heating apparatus (Huber Ministat 230-CC), a sparging stirrer (Pt 100, 7 bar safety valve, gas connections with QC quick-release couplings), a pressure reducer for the pressure range of 0-10 bar, and optionally a flowmeter at the gas inlet and a pressure regulator, i.e. pressure release valve, at the gas outlet. (0121) Unless stated otherwise, the following standard conditions were used for the catalytic isomerization experiments which follow: (0122) Stirrer speed: 1000 rpm (0123) Exchange rate of oxygenous gas: 30 L/h (0124) Reaction temperature: 80° C. (0125) Pressure in the reactor: 5-20 bar (0126) Amount of feedstock: 100 g (0127) The catalytic isomerization experiments were conducted with various Pd catalysts. The results of the experiments are compiled in table 1. As apparent from table 1, carbon-supported Pd catalysts show thee desired activity. In general, total selectivities, i.e. the selectivities of prenol and prenal together, of more than 90% are attained. It was possible to successfully implement recycling of the catalyst and subsequent reuse. In addition, it was generally possible to identify a decline in the formation of isoamyl alcohol by virtue of the reaction conditions used; the values were in a range of 0.5-1.0 area %. (0129) Table 2 shows the profile of the conversion of MBE against time and the amount of prenol and prenal formed in a representative catalytic isomerization reaction. |
With pyridine; 2-methyl-2-phenyloxirane; iron pentacarbonyl; carbon monoxide at 70℃; for 42h; Inert atmosphere; Autoclave; | 2 Example 2 Under the protection of nitrogen atmosphere,2 g (10 mmol) of iron pentacarbonyl and 0.65 g (5 mmol)2-phenylpropylene oxide was mixed and stirred at room temperature for 12 hours.After adding 8g (100 mmol) of pyridine,Stir at room temperature for 6 h.Transfer the mixture to an autoclave and add it17.2 g (0.2 mol) of 3-methyl-3-butenol and 150 g of polyethylene glycol 200.The reactor was replaced 10 times with nitrogen containing 10 000 ppm of carbon monoxide,The reactor was heated to 70°C.Pressure 0.5MPa,Stir for 24 h. The organic phase was analyzed by gas chromatography.The conversion rate was 79.8% and the selectivity was 99.0%. |
With 1,3-bis-(diphenylphosphino)propane; hydrogen; palladium diacetate In acetone at 55℃; for 1h; Autoclave; | 1; 2; 3; 4; 5; 6; 7 Example 1 Weigh 0.165 g of bisphosphine ligand 1,3-bis (diphenylphosphine) propane (DPPP), 0.089 g of transition metal compound such as palladium acetate, add to a three-necked flask, add 100 ml of acetone, and replace with nitrogen 3 times, 28 ° C Stir for 25min, then stop the reaction and spin-dry in vacuum at 50 ° C to obtain 0.15g of the chelated complex catalyst.150 g of 3-methyl-3-buten-1-ol and 0.15 g of the catalyst prepared by the above method were added to a 500 m autoclave. After nitrogen replacement 3 times, the pressure of hydrogen was maintained at 0.7 MPa, the temperature was controlled at 55 ° C, and the rotation speed was 200 rpm. After 60 minutes of reaction, the reaction was stopped, and the gas was drawn out to obtain 150 g of isopentenol, with a selectivity of 95.21% and a conversion rate of 79.18%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2-methyl-1-buten-4-ol; acetic acid With A-36 ion exchange resin at 100℃; Autoclave; Large scale; Stage #2: With hollow molecular sieve nanotubes supported silicotungstic acid catalyst at 105 - 155℃; Large scale; | 1 Esterification reaction In a 5 L stainless steel stirred tank (prereactor 1), 1 L of A-36 ion exchange resin (Dow Corporation) was added as a catalyst for the esterification prereactor, and the raw material acetic acid powder was fed at 2 kg/h, and 10 kg/ h isopentenol (3-methyl-3-buten-1-ol) was dissolved and mixed in a pre-reactor; at a pressure of 1.6 BarA at 100 °C, partial esterification occurred, and the conversion of acetic acid was 70%. ;The reaction liquid is sent to the upper portion of the rectifying section of the catalytic rectification column 3. The catalytic distillation column has a diameter of DN80, 10 theoretical plates of the rectifying section and the stripping section, and the reaction section is 8 meters high. 20 trays are arranged, and the height of the rising pipe is 150 mm. The catalyst was a heteropolyacid catalyst prepared as described above, and the catalyst loading amount was 8 L. The catalytic distillation column reaction pressure is 110kPaA, the temperature at the top of the column is 105 °C, and the temperature of the column is 155 °C. After the operation is stable, the tower is sampled and sent to GC for analysis. The acetic acid conversion rate is >99.9%, and the product acid value is <100 mg KOH/kg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With ammonium cerium (IV) nitrate In methanol at 0 - 20℃; Inert atmosphere; | General procedure for the synthesis of derivatives 3, 5, 7, 9, 10, and 12 General procedure: To a stirred solution of 1, 4, or 6 (2.0 mmol) and corresponding alkenol (2.2 mmol) in 10 cm3 MeOH or 10 cm3 MeCN (for 6) at 0 °C under Ar was added dropwise solution of 2.35 g CAN (4.2 mmol) in 20 cm3 MeOH or 20 cm3 MeCN during 15 min. The mixture was then stirred at room temperature until the completion of reaction was confirmed by TLC (15-45 min). After addition of 20 cm3 water and removal of the organic solvent in vacuo, the residue was extracted with dichloromethane (3 9 15 cm3). Combined extracts were washed with 10 cm3 saturated solution of NaHCO3 and 10 cm3 brine and dried over anhydrous Na2SO4. Evaporation of the solvent gave a yellowish oil which was chromatographed on silica gel with n-hexane-AcOEt mixtures of increasing polarity (starting from 1:1). All the compounds synthesized were obtained as colorless oils. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With phosphoric acid; In water; at 120℃; under 1500.15 Torr;Autoclave; | 300 g of a 1.8% by mass phosphoric acid aqueous solution was charged in a Hastelloy-made 500-mL autoclave; the inside of the autoclave was purged with nitrogen and then pressurized with nitrogen to 0.7 MPa; and heating and stirring (1,000 times/min) were commenced. When the inner temperature reached 170 C., 75.9 g/hr of 3-methyl-3-buten-1-ol obtained in the step A? and 79.4 g/hr of water [water/3-methyl-3-buten-1-ol=5.0/1.0 (molar ratio)] were fed into the autoclave.When the internal pressure reached 0.85 MPa, release of the gas within the autoclave was commenced so as to keep the foregoing pressure. The released gas was continuously cooled by a condenser attached to the autoclave, to coagulate the reaction product, and the operation was continued for 4 hours while receiving the reaction product in a tank.As a result of analyzing the organic layer within the tank and the reaction liquid within the reactor by means of gas chromatography, the conversion of 3-methyl-3-buten-1-ol was 98.2%, and the selectivity of isoprene was 93.1%. In addition, the selectivities of isobutene, 2-methyl-3-buten-2-ol, 3-methyl-1,3-butanediol, methyl isopropyl ketone, and an isoprene dimer, all of which are byproducts, were 1.9%, 0.6%, 0.3%, 0.9%, and 2.8%, respectively. The results are shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With bis(cyclopentadienyl)titanium dichloride; 3,5-dinitrosalicylic acid In dichloromethane at 20℃; for 5h; Schlenk technique; | 1 Synthesis of 4-chloro-4-methyl-2-(4-nitrophenyl)-tetrahydropyran as follows 0.1511 g (1.0 mmol) of p-nitrobenzaldehyde, 151 μL (1.5 mmol) of 3-methyl-3-buten-1-ol, 0.248 g (1.2 mmol) of dichlorotitanocene, 0.2281 g (1.0 mmol) 3,5-dinitrosalicylic acid, 3 mL of dry dichloromethaneThe Shrek tube was added thereto, and the reaction was stirred at normal temperature for 5 hours, the reaction was stopped, and the column chromatography was carried out to obtain a solid 4-chloro-4-methyl-2-(4-nitrophenyl)-tetrahydropyran.The yield was 88% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With bis(cyclopentadienyl)titanium dichloride; iodine; 5-sulfosalicylic Acid; potassium iodide In dichloromethane at 20℃; for 4h; | 1 Synthesis of 4-iodo-4-methyl-2-(4-nitrophenyl)-tetrahydropyran as follows 0.1511 g (1.0 mmol) of p-nitrobenzaldehyde, 131 μL (1.3 mmol) of 3-methyl-3-buten-1-ol, 0.0248 g (0.1 mmol) of dichlorotitanocene, 0.254 g (1.0 mmol) of 5-sulfosalicylic acid, 0.1666 g (1.0 mmol) of potassium iodide, 0.127 g (1.0 mmol) of iodine and 3 mL of dry dichloromethane were added in a Shrek tube, and stirred at room temperature for 4 hours. After completion of the reaction, the resulting mixture was separated by column chromatography to obtain solid 4-iodo-4-methyl-2-(4-nitrophenyl)-tetrahydropyran. The yield is 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With bis(cyclopentadienyl)titanium dichloride; 5-sulfosalicylic Acid; 1-butyl-2,3-methylimidazolium tetrafluoroborate In dichloromethane at 20℃; for 5h; Schlenk technique; | 1 Synthetic structure is as follows4-fluoro-4-methyl-2-(4-nitrophenyl)-tetrahydropyran 0.1511 g (1.0 mmol) of p-nitrobenzaldehyde,131 μL (1.3 mmol) of 3-methyl-3-buten-1-ol,0.0248g (0.1mmol)Titanium dichloride,5-sulfosalicylic acid0.07626g (0.3mmol), 0.4800g (2.0mmol)1-butyl-2,3-dimethylimidazolium tetrafluoroborate, 3 mLDry methylene chloride is added to the Shrek tube.The reaction was stirred at room temperature for 5 hours, the reaction was stopped, and column chromatography was carried out.Obtaining the solid 4-fluoro-4-methyl-2-(4-nitrophenyl)-tetrahydropyran,The yield is 83% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; Inert atmosphere; | |
94.7% | With toluene-4-sulfonic acid In toluene at 100 - 105℃; for 5h; | 5 Example 5: Preparation of 2-methyl-4-palmitoyloxy-1-butene (2) Add 300 g of toluene and 86.0 g (1.0 mol) of 2-methyl-4-hydroxy-1-butene (II) into a 1000 ml four-necked flask connected with a stirrer, thermometer, water trap and reflux condenser. 270.0 g (1.05 mol) palmitic acid, 0.5 g p-toluenesulfonic acid, azeotropically remove water at 100-105°C and stir for 5 hours. Cool to 60-65, change to vacuum distillation system, distill and recover first toluene, then changed to high vacuum distillation (130-145°C/1-2mmHg) to obtain 307.3 g of 2-methyl-4-palmitoyloxy-1-butene (2), the yield was 94.7%, gas phase The purity is 99.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h; Inert atmosphere; | |
86% | With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; Inert atmosphere; | |
78% | With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; Inert atmosphere; |
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h; Inert atmosphere; | ||
With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 47% 2: 3% | With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In ethanol; dichloromethane; water at 20℃; for 0.833333h; | 3.2. Representative Procedure, Synthesis of (2,2-Dibromo-3,3-dimethylcyclopropyl)methanol (1) General procedure: A 1.0 mL sample loop (PTFE) containing a solution of 3-methyl-2-buten-1-ol (1.43 mmol), CHBr3 (2.86 mmol), 4.3 mol% TEBA (relative to the alkene) and 0.6 vol.% ethanol (absolute) in CH2Cl2, and a 5 mL sample loop (PTFE, Syrris Ltd.) containing 40% (w/w) NaOH (aq) solution, was used. The filling of the 40% (w/w) NaOH (aq) solution into the sample loop was done very slowly and with great care, due to the high viscosity of the strongly basic NaOH solution and danger of spillage due to pressure build-up. The two solutions were simultaneously introduced into the flow system at a total flow rate of 0.50 mL/min (flow rate NaOH (aq): 0.40 mL/min, flow rate organic solution: 0.10 mL/min) at room temperature, i.e., a residence time of 50 min and an AO flow ratio of 4. The mixture was fed into brine (50 mL), and the flow was collected for 77 min at this flow rate, and then for 4 min at 2 × 1.5 mL/min (to flush the system). The pressure in the system was 1-4 bar. The reaction mixture was extracted with ethyl acetate (100 mL + 3 × 50 mL), and the combined organic phases were washed with brine (2 × 50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by filtering it through a plug made of 0.5 cm silica and 0.5 cm Celite 545 coarse (calcined) using ethyl acetate as the eluent. Concentration in vacuo yielded a mixture (0.31 g) containing (2,2-dibromo-3,3- dimethylcyclopropyl)-methanol (1): 3-methyl-2-buten-1-ol: bromoform; 88:2:10 according to 1H NMR. Estimated yield of 1: 0.27 g, 74%, corresponding to a space time yield of ~0.25 mol L-1 h-1. The spectral data were in accordance with the literature [46]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 12h; | 3-Methylbut-3-en-1-yl 3-(4,5-diphenyloxazol-2-yl)propanoate (8), 4,5-Diphenyl-2-oxazolepropanoic acid (10 mmol) was added to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC, 15 mmol) and DMAP (0.2 mmol) in CH2Cl2 (20 mL) at 0 °C. 3-Buten-1-ol (1.03 g, 12 mmol) was then added. The resulting mixture was allowed to warm up to room temperature and stirred for 12 h. The solution was diluted with ethyl acetate (150 mL) and washed with 1N HCl solution. The aqueous layer was then extracted twice with ethyl acetate (100 mL). The combined organic layer was dried over anhydrous Na2SO4. After the removal of solvent under reduced pressure, the crude product was purified by column chromatography on silica gel with ethyl acetate/hexane as the eluent to give pure 8 as a colorless oil. Yield: 3.25 g (90% yield). Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 6.7 Hz, 2H), 7.58 (d, J = 7.0 Hz, 2H), 7.42 - 7.29 (m, 6H), 4.77 (d, J = 23.7 Hz, 2H), 4.26 (t, J = 6.8 Hz, 2H), 3.19 (t, J = 7.1Hz, 2H), 2.92 (t, J = 7.5 Hz, 2H), 2.36 (t, J = 6.8 Hz, 2H), 1.75 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 172.00, 161.81, 145.46, 141.59, 135.20, 132.54, 129.06, 128.69, 128.60, 128.50, 128.11, 127.95, 126.53, 112.39, 76.84, 63.01, 36.73, 31.23, 23.63, 22.52; IR (film): ν (cm-1) 3060, 2969, 1736, 1605, 1571, 1502, 1444, 1356, 1221, 1167, 1025, 962, 763, 694; HRMS (ESI): Calcd for [C23H23NO3+H]+: 361.1678, found: 361.1682. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.3% | With toluene-4-sulfonic acid In toluene at 100 - 105℃; for 4h; | 1 Example 1: Preparation of 2-methyl-4-acetoxy-1-butene (III1) Into a 500 ml four-necked flask connected with a stirrer, a thermometer, a water trap and a reflux condenser, add 300 g of toluene, 86.0 g (1.0 mol) of 2-methyl-4-hydroxy-1-butene (II), 72.0 g (1.2 moles) of acetic acid, 0.5 g of p-toluenesulfonic acid, azeotropically remove water at 100-105°C, and stir for 4 hours. Cool to 60-65, change to vacuum distillation system, first distill toluene and excess acetic acid, then change to high vacuum vacuum distillation (60-75/1-2mmHg) to obtain 124.6g 2-methyl-4- Acetoxy-1-butene (III1), the yield was 97.3%, and the gas phase purity was 99.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 2-methyl-1-buten-4-ol With methanesulfonyl chloride; triethylamine In toluene at 0 - 15℃; for 1h; Stage #2: Diphenylacetonitrile With tetrabutylammomium bromide; sodium hydroxide In water; toluene at 103 - 111℃; | 1 Example 1 : Preparation of 5-methyi-2,2-diphenyIhex-5-enenitriie (diphenyl alkene) To a stirred solution of 3-methyl-3-buten-l-ol (100 gm), toluene (1000 ml) and triethylamine (141 gm) at 0-5 °C, methanesulfonyl chloride (146.3 gm) at about 1 5 °C was added and the reaction mass stirred for 60 minutes. To the above reaction mass, 1.0% HC1 (500 ml) at room temperature (RT) was added and the resulting mixture stirred for 15-20 minutes, the organic layer was separated and washed with water (500 ml), and then washed with 10% brine solution (500 ml). To the above toluene solution, diphenylacetomtrile (230 gm), tetrabutylammonium bromide (TBAB) (73 gm) and a solution of sodium hydroxide water (226.5 g in 197 ml) was added and stirred at 103-111 °C. Water was collected through azeotrope, and upon complete conversion, water (1400 ml) was added and stirred. The organic layer was separated, further washed with 0.5% HC1 (745 ml), and then the organic layer was distilled completely and eo-distilled with isopropyl alcohol (100 ml). To the above residue, isopropyl alcohol (370 ml) and water (185 ml) were added and the mixture stirred for a period of 30 minutes. A thick slurry was formed which was filtrated followed by washing with isopropyl alcohol (IP A): water (1 : 1 ratio) (370 ml x 2). The product was then dried in a vacuum to produce 5-methyl-2,2-diphenylhex-5-enenitrile (diphenyl alkene). The product was in an amount of about 260 grams (85%) as an off white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triphenylphosphine In tetrahydrofuran at 0℃; Inert atmosphere; | 9.8 Step 8: N-(2-(benzyloxy)pyrazolo[1,5-a]pyridin-6-yl)-4-methyl-N-(3-methylbut-3-en-1- yl)benzenesulfonamide To a stirred solution of 3-methylbut-3-en-1-ol (385 mg, 4.5 mmol), triphenylphosphane (2.1 g, 8.1 mmol) and N-(2-benzyloxypyrazolo[1,5-a]pyridin-6-yl)-4-methyl-benzenesulfonamide (1.6 g, 4.0 mmol) in THF (50 mL) was added isopropyl N-isopropoxycarbonyliminocarbamate (2 M, 4.1 mL) dropwise at 0 °C under nitrogen. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, using PE/EtOAc (5:1) as eluent to afford N-(2-benzyloxypyrazolo[1,5-a]pyridin-6-yl)-4-methyl-N-(3-methylbut-3- enyl)benzenesulfonamide (1.5 g, 80% yield) as a white solid. LC-MS: m/z 462 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 3h; Inert atmosphere; | A.2 Step 2: To a solution of N-(6-chloropyridin-3-yl)-4-methylbenzenesulfonamide (1.00 g, 3.53 mmol), 3-methyl-3-buten-1-ol (0.31 g, 3.60 mmol) and triphenylphosphine (1.40 g, 5.34 mmol) in tetrahydrofuran (10 mL) was added diisopropyl azodiformate (1.10 g, 5.44 mmol) dropwise at 0 °C under nitrogen atmosphere. The mixture was warmed to room temperature for 3 h. The mixture was concentrated under vacuum. The residue was purified by flash column chromatography with 0-20% ethyl acetate in petroleum ether to afford N-(6-chloropyridin-3-yl)-4-methyl-N-(3-methylbut-3-en-1-yl)benzenesulfonamide (1.10 g, 88%) as a colorless oil. MS m/z 351.1 [M+1]+. 1H NMR (300 MHz, Chloroform-d) d 7.95 (d, J = 1.5 Hz, 1 H), 7.47 - 7.44 (m, 3H), 7.33 - 7.27 (m, 3H), 4.78 (s, 1 H), 4.59 (s, 1 H), 3.66 (t, J = 1.2 Hz, 2H), 2.43 (s, 3H), 2.13 (t, J = 7.2 Hz, 2H), 1.70 (s, 3H). |
Tags: 763-32-6 synthesis path| 763-32-6 SDS| 763-32-6 COA| 763-32-6 purity| 763-32-6 application| 763-32-6 NMR| 763-32-6 COA| 763-32-6 structure
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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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