There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 112-42-5 | MDL No. : | MFCD00004751 |
Formula : | C11H24O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KJIOQYGWTQBHNH-UHFFFAOYSA-N |
M.W : | 172.31 | Pubchem ID : | 8184 |
Synonyms : |
Undecyl alcohol;1-Hendecanol;Undecanol;Tip-Nip;Decyl carbinol;C11 alcohol;Alcohol, undecyl
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 9 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 56.15 |
TPSA : | 20.23 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.09 cm/s |
Log Po/w (iLOGP) : | 3.28 |
Log Po/w (XLOGP3) : | 4.59 |
Log Po/w (WLOGP) : | 3.51 |
Log Po/w (MLOGP) : | 3.13 |
Log Po/w (SILICOS-IT) : | 3.45 |
Consensus Log Po/w : | 3.59 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.21 |
Solubility : | 0.107 mg/ml ; 0.000622 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.74 |
Solubility : | 0.00314 mg/ml ; 0.0000182 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -3.73 |
Solubility : | 0.0317 mg/ml ; 0.000184 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 3.0 |
Synthetic accessibility : | 1.75 |
Signal Word: | Danger | Class: | 9 |
Precautionary Statements: | P273-P280-P302+P352+P312-P305+P351+P338+P310-P312-P362+P364-P391-P501 | UN#: | 3082 |
Hazard Statements: | H303-H312-H318-H411 | 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 |
---|---|---|
97% | With 4-hydroxy-TEMPO benzoate; sodium bromide In dichloromethane; water NaHCO3-buffered at pH 8.6, electrolysis; also with other reagents and varying amounts of reagents; | |
97% | With 4-hydroxy-TEMPO benzoate; sodium bromide In dichloromethane; water NaHCO3-buffered at pH 8.6; electrolysis; | |
97% | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; oxone; potassium bromide In acetonitrile at 0℃; for 4h; |
97% | With 4-(benzyloxycarbonyl)-2,2,6,6-tetramethylpiperidine-1-oxyl; [bis(acetoxy)iodo]benzene; toluene-4-sulfonic acid In TETRAHYDROPYRANE at 20℃; for 0.5h; | |
95% | With 4-hydroxy-TEMPO benzoate; sodium acetate; tetra-N-butylammonium tribromide In dichloromethane; water at 20℃; for 1h; pH's from 4 to 11, different reaction times, various amounts and absence of 4-benzoyloxy-2,2,6,6-tetramethyl-1-piperidinyloxyl; | |
95% | With 4-hydroxy-TEMPO benzoate; sodium acetate; tetra-N-butylammonium tribromide In dichloromethane at 20℃; for 1h; | |
93% | With sodium bromite; 4-benzoxy-2,2,6,6-tetramethylpiperidine-N-oxyl; sodium hydrogencarbonate In dichloromethane; water for 3h; Ambient temperature; also with Ca(OCl)2 (90 percent yield); | |
93% | With 4-methoxy-2,2,6,6-tetramethyl-1-piperidinyloxy; sodium hypochlorite; potassium bromide In dichloromethane; water at 0℃; for 0.05h; pH = 8.6; | |
92% | With cetyltrimethylammonium bromochromate In dichloromethane for 0.833333h; Heating; | |
92% | With sodium hypochlorite; 4-([4-(triphenylphosphonio)benzyl]oxy}carbonyl)oxy-2,2,6,6-tetramethylpiperidin-1-oxyl perchlorate; sodium hydrogencarbonate; potassium bromide In dichloromethane; water for 0.166667h; | |
92% | Stage #1: undecyl alcohol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.25h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; | Undecanal (4) A pre-prepared solution of DMSO (0.87 mL) in 9 mLof dichloromethane (DCM) was added dropwise to a stirredsolution of oxalyl chloride (0.6 mL, 6.3 mmol) in DCM(7.8 mL) at -78 °C. After 5 min, a solution of 1-undecanol(Sigma-Aldrich, USA) (3) (900 mg, 5.2 mmol) in DCM(7.5 mL) was added. The resulting mixture was stirred for15 min at -78 °C, and triehtylamine was added (3.6 mL,26 mmol). After 10 min, the temperature was increasedto room temperature, and DCM (30 mL) was added. Theresulting mixture was washed with saturated solutions ofNH4Cl and brine and dried with Na2SO4. The solvent wasevaporated under reduced pressure, and the residue was purified by flash chromatography, furnishing undecanal (4)in 92% yield (816 mg, 4.8 mmol) |
91% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite pentahydrate; sodium hydrogencarbonate; potassium bromide In water for 0.333333h; Milling; | General procedure for the oxidation of primary alcohols 1a-10b (procedure A) General procedure: NaOCl·5H2O (247 mg, 1.5 mmol), NaHCO3 (185 mg, 2.2 mmol), and KBr (3.6mg, 0.03 mmol, 3 mol%) were placed in an Ertalyte jar (15 mL, 40.6 g) equippedwith six zirconia balls (5 mm ). The jar was ball-milled at 1800 rpm (30 Hz) for1 min. Following this initial grinding period, primary alcohol 1a-10a (1.0 mmol),and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO, 7.8 mg, 0.05 mmol, 5 mol %),were added and the reaction mixture was subjected to further grinding at 30 Hzfor 20 minutes. The progress of the reaction was monitored by GC-MS analysisand TLC analysis (heptane/AcOEt 9:1, v/v) of an aliquot of crude. The millingwas stopped, Na2SO3 (189 mg, 1.5 mmol) added to the jar, and milling continuedat 30 Hz for further 3 minutes. Then, AcOEt (2 × 1.5 mL) was added into the jarand the crude was transferred into a round-bottomed flask together with silica gel(350 mg). The combined organic layers were concentrated in vacuo. The resultingresidue was purified through a short column on silica gel with ethylacetate/hexane 1:9 (v/v) as the eluent to afford the corresponding aldehydes 1b-10b |
90% | With triethylammonium fluorochromate(VI) In dichloromethane for 0.833333h; Heating; | |
90% | With trimethylammonium fluorochromate In dichloromethane for 0.9h; Heating; | |
90% | With 2,4,6-trimethyl-pyridine; 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinoxy; iodine; sodium hydrogencarbonate In dichloromethane; water at 20 - 22℃; for 2h; | 1.10 Preparative synthesis of compounds 2a,b,d-al (general procedure) General procedure: A solution of corresponding alcohol 1a,b,d-al (8 mmol), nitroxide 4a (0.085 g, 0.4 mmol) and compound 6d (0.097 g, 0.8 mmol) in CH2Cl2 (10 mL) was added to a vigorously stirred solution of NaHCO3 (2.016 g, 24 mmol) in water (10 mL) at 20 °C. Then I2 (4.06 g, 16 mmol) powder was added in one portion to the formed reaction mixture at vigorous stirring and temperature 20-22 °C. The reaction mixture was stirred at 20-22 °C for appropriate time (see Table 1 in the article). Then, a saturated solution of sodium thiosulfate was added to the stirred reaction mixture for discoloration. Organic and aqueous phases were separated and the aqueous phase was then extracted with CH2Cl2 (3×5 mL). Organic phase and the extracts were combined and washed subsequently with saturated aqueous solution of NaCl (5 mL), aqueous solutionof HCl (1%) saturated with NaCl (3 mL), and then with water (5 mL). The washed extract was dried with anhydrous Na2SO4 and evaporated to dryness to give crude product, which was then purified by vacuum distillation under argon atmosphere or by recrystallization. |
80% | With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; for 2h; | |
80% | With [bis(acetoxy)iodo]benzene; fluorous-tagged TEMPO radical In dichloromethane at 20℃; for 2h; | |
76% | With oxygen; tetrabutylammonium acetate In toluene at 60℃; for 10h; | |
74% | With bis-trimethylsilanyl peroxide In dichloromethane for 0.5h; | |
73.7% | With ruthenium(IV) oxide; tetrabutylammomium bromide; tetra(n-butyl)ammonium hydroxide In water; acetonitrile electrooxidation on Pt electrodes; | |
71% | With tris(triphenylphosphine)ruthenium(II) chloride; 4-hydroxy-TEMPO benzoate; oxygen In toluene at 70℃; for 8h; | |
38% | With imidazolium dichromate In N,N-dimethyl-formamide for 24h; Ambient temperature; | |
With 4-methylmorpholine N-oxide In acetonitrile at 25℃; | ||
With nickel at 250℃; | ||
100 % Chromat. | With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutyl-ammonium chloride; sodium hydrogencarbonate; sodium chloride; potassium bromide In dichloromethane; water 1) 0 deg C, 1h, 20 deg C, 20 min; | |
With pyridinium chlorochromate In dichloromethane | ||
93 % Chromat. | With sodium hypochlorite In dichloromethane; water at 0℃; for 0.5h; | |
100 % Chromat. | With sodium hypochlorite; poly(ethylene glycol)-supported 4-hydroxy-TEMPO-derivative; sodium bromide In dichloromethane; sodium hydrogencarbonate at 0℃; for 0.0833333h; | |
With manganese(II) nitrate; 4-(p-(MeO(CH2CH2O)n-CH2CH2-O)C6H4(CH2)3O-p-C6H4CH2O)-TEMPO; oxygen In acetic acid at 40℃; for 4h; | ||
With manganese(II) nitrate; FibreCatTM-supported 2,2,6,6-tetramethylpiperidine-N-oxyl; oxygen In acetic acid at 40℃; for 3h; | ||
Ca. 45 %Chromat. | With acetaldehyde at 30℃; for 24h; aq. phosphate buffer; Microbiological reaction; Combinatorial reaction / High throughput screening (HTS); chemoselective reaction; | |
With microsomal alcohol oxidase from Aspergillus terreus at 25℃; for 24h; aq. buffer; | ||
With sodium hypochlorite; potassium bromide In dichloromethane; water at 5℃; for 0.166667h; | ||
With phenol resin supported dehydrogenation CuFeAl catalyst at 220℃; for 10h; Flow reactor; Inert atmosphere; | 2 (Production of undecyl aldehyde under partial pressure of alcohol of 7 kPa using the film-type dehydrogenation catalyst containing phenol resin as binder) The film-type dehydrogenation catalyst obtained in Production Example 1 was bent into a corrugated plate shape. The bent film-type dehydrogenation catalyst and a planar film-type dehydrogenation catalyst were stacked alternately, and packed in the stainless reaction tube 14 (inner diameter: 28 mm, tube length: 150 mm, flow reactor) (packed amount of the powdered catalyst: 3.2 g). The vaporization tube 13 (made of stainless, inner diameter: 2 mm, tube length:1500 mm) and the gas preheating portion 23 were connected to the inlet of the reaction tube 14, and the cooling tube 16 and the fractionator 17 were connected to the outlet of the reaction tube 14 (see FIG. 1). The vaporization tube 13 and the gas preheating portion 23 were heated at 320°C for 12 minutes using the heating portion 15. Undecyl alcohol was supplied from the starting material alcohol supply portion 11 to the reaction tube 14 via the starting material alcohol supply tube 31 at a speed of 15 g/hour and nitrogen was supplied from the gas supply portion 21 to the reaction tube 14 via the gas supply tube 32 at a speed of 12.0 L/hour. In this case, in the mixed gas of the vaporized undecyl alcohol and nitrogen gas, the partial pressure of undecyl alcohol was 7 kPa. Thereafter, the internal temperature of the reaction tube 14 was raised to 220°C by the heating portion 15. At this time, the reaction pressure was 50 kPa. A product generated inside the reaction tube 14 reached the cooler 16 cooled at 40°C via the product collection tube 33. The product passed through the cooler 16 was separated in the fractionator 17, and extracted with time via the liquid product collector 34. Thus, undecyl aldehyde was obtained. Table 1 shows evaluation results of the obtained product. | |
With oxygen In hexane at 19.84℃; for 5h; Green chemistry; | ||
97 %Chromat. | With [2,2]bipyridinyl; Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; acetic acid at 25℃; for 8h; | |
53 %Chromat. | With 5-nitroso-1,3-diphenyltetrazolium tetrafluoroborate; oxygen; nitric acid In acetonitrile at 20℃; for 8h; | |
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; laccase from Trametes versicolor; sodium dodecyl-sulfate In aq. phosphate buffer at 20℃; for 24h; Enzymatic reaction; | ||
2 %Chromat. | With sodium hypochlorite pentahydrate In acetonitrile at 20℃; for 1h; | |
87 %Chromat. | With 1-methyl-1H-imidazole; [2,2]bipyridinyl; copper(l) iodide; 1,3-diphenyltetrazolium-5-hydroxyamide; oxygen In acetonitrile at 20℃; for 24h; chemoselective reaction; | General Procedure for the Optimization of the Cu-1-CatalyzedAerobic Oxidation of Benzyl Alcohol (Table 1): General procedure: Amixture of benzyl alcohol 2a (0.4 mmol), Cu salt (0.02 mmol)ligand (0.02 mmol), base (0.04 mmol), and 1 (0.02 mmol) wasvigorously stirred in MeCN (4.0 mL) at room temperature for 24h in the presence of PhCN (0.2 mmol) as an internal standard. Atintervals, aliquots were analyzed by GC after being passedthrough a SiO2 column eluted with CH2Cl2. The yield of benzaldehyde3a (tR = 4.3 min) and the recovery of 2a (tR = 9.4 min)were calculated on the basis of calibration curves by usingauthentic samples |
46 %Chromat. | With 1,10-Phenanthroline; 1,2-bis(t-butyloxycarbonyl)hydrazine; caesium carbonate; copper(l) chloride In toluene at 20℃; for 3h; | |
With acetonitrile(cyclopentadienyl)[2-(di-i-propylphosphino)-4-(t-butyl)-1-methyl-1H-imidazole]ruthenium(II) hexafluorophosphate at 70℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With whole cell cultures of dichomitus albidofuscus at 24℃; for 192h; Darkness; Microbiological reaction; | 2.5. general procedure for preparative biotransformation General procedure: The substrate (1 mmol) was added to submerged cultures of DAL on the 3rd culture day. The reaction mixture was incubated on an incubation shaker at 150 rmin 1 (deflection 25 mm) under exclusion of light at 24 °C for 4 days. 10 g of NaCl was added to media, and the mixture was stirred for 10 min at 800 rpm (magnetic stirrer). For extraction, 50 mL of Et2O was added, and the resulting mixture was stirred for 20 min at 800 rpm (magnetic stirrer), and centrifuged for 5 min at 3000 × g to separatethe organic layer. The extraction was repeated three times. The combined organic layers were washed with brine (1 × 30 mL) and water (1× 30 mL), dried over Na2SO4 and evaporated to dryness. The resulting reaction mixtures were analysed by GC/MS and NMR spectroscopy.Products were purified by column chromatography on silica gel (eluent(pentane/ether) changed gradually: 10/1, 7/3, 1/1) to isolate the majorcomponents. The respective fractions were combined, concentrated in vacuum, and the 1H and 13C NMR spectra of the residuals were compared with those of reference compounds. Every biotransformation was repeated three times to verify the reproducibility of the experiments. The detailed information about experimental data and yields is provided in the Electronic Supplementary Information. |
93% | With mer-[RuCl3(1,4-bis(diphenylphosphino)butane)(4-vinylpyridine)]; hydrogen In methanol at 160℃; for 24h; Autoclave; | Catalytic studies General procedure: Hydrogenation reactions were performed in 25 and 75mL stainless steel autoclaves equipped with an overhead magnetic stirrer, a pressure indicator and a thermocouple for temperature registration. The autoclaves were equipped with an electrical heating/cooling system to control the temperature inside the vessel. The hydrogenation active catalyst substrate/Ru-complex was prepared in situ, once the Ru-complexes used were pre-catalysts. The autoclave was charged with Ru-complex (0.013, 0.015 or 0.026mmol), substrate (1.5 or 6.9mmol), MeOH (20 or 6mL). The system was flushed three times with H2. Then, the autoclave was pressurized with H2 (15, 50 or 100bar) and heated to a temperature of 80 or 160°C, for 15 or 24h. After the reaction, the homogeneous reaction mixture was cooled down in an ice bath to room temperature, and the upper organic layer was analyzed by GC-FID and GC-MS |
77% | With formic acid; water; palladium diacetate; tricyclohexylphosphine In 1,4-dioxane at 90℃; for 6h; Inert atmosphere; Sealed tube; chemoselective reaction; | Typical procedure and Spectral Data for Products General procedure: An oven-dried pressure tube containing a Teflon-coated stirring bar was charged with Pd(OAc)2 (11.2 mg, 5 mol%), PCy3 (21 mg, 7.5 mol%) and aldehyde(1 mmol).The tube was sealed, evacuated and backfilled with N2. 1 mL of dioxane was subsequently injected. After the mixture was stirred at room temperature for 15 min, H2O (180 mg, 10 equiv) and HCO2H (184 mg, 4 equiv) were injected and the reaction was heated to 90 oC for 18 h. After the reaction was completed, the solvent was removed under vacuo. The residues were purified by flash column chromatography on silica gel to afford 87 mg of benzyl alcohol in 81 % yield. |
62% | With lithium-<cyano(triphenylphosphoranyliden)methyl>trihydroborate In tetrahydrofuran at 70℃; for 48h; | |
With acetic acid; zinc neben einen Kondensationsprodukt; | ||
With Trimethylammoniumessigsaeurebetain-methylester-chlorid Yield given. Multistep reaction; | ||
With ruthenium trichloride; trisodium tris(3-sulfophenyl)phosphine; heptakis(2,6-di-O-methyl)cyclomaltoheptaose; hydrogen; sodium iodide In water; toluene at 80℃; for 0.5h; | ||
With potassium phosphate buffer; pig testicular 20β-hydroxysteroid dehydrogenase; NADPH at 37℃; | ||
Multi-step reaction with 2 steps 1: Tetrabutylammonium fluoride / hexamethylphosphoric acid triamide / 4.5 h / Ambient temperature 2: conc. HCl / methanol | ||
96.8 %Chromat. | With Shvo's catalyst; hydrogen In N,N-dimethyl acetamide at 120℃; for 1h; Autoclave; | |
91 %Chromat. | With acetylacetonatodicarbonylrhodium(l); 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); carbon monoxide; hydrogen In 1,4-dioxane at 120℃; for 18h; Autoclave; Inert atmosphere; | |
42 %Chromat. | With {2,5-(C6H5)2-3,4-(4-MeOC6H4)2C4CO}2H(μ-H)(CO)4Ru2; carbon monoxide; hydrogen In N,N-dimethyl acetamide at 120℃; for 4h; Schlenk technique; Inert atmosphere; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With carbon dioxide; hydrogen at 60℃; | |
97% | With ethanol; (BQ‑NCOP)IrHCl; sodium t-butanolate at 60℃; for 2h; Inert atmosphere; Schlenk technique; Sealed tube; | |
94% | With sodium tetrahydroborate; ruthenium(III) trichloride hydrate In 1-methyl-pyrrolidin-2-one; water at 0℃; for 1h; chemoselective reaction; | General procedure for alkene reduction General procedure: To a 15-mL 1-neck reaction flask fitted with a glass stopper [Note: A larger-scale reaction may require the use of a pressure vessel and/or addition of NaBH4 in small portions.] were added a small spin bar, 0.18-0.20 mmol of substrate, 0.60 mL of 5:1 (v/v) [10:1 (v/v) in Table 1, entry 3] liquid amide(s)/H2O, and 7.0 mg (0.034 mmol) of ruthenium(III) chloride hydrate (Sigma-Aldrich Catalog No. 206229). After cooling the latter mixture to 0 C (external ice-H2O bath), 9.0 mg (0.24 mmol) of NaBH4 powder was added in one portion; and the mixture was subsequently stirred at 0 C for 60 min. The reaction was then quenched by addition of 2.0 mL of 2 M aqueous HCl to the reaction flask, followed by 1.0 mL of pentane and subsequent stirring of the mixture at 0 C for 15 min. The product was then isolated by dilution of the reaction mixture with 10 mL of 4:1 (v/v) pentane/dichloromethane; and solid material was removed by filtration through a small pad of Hyflo Super-Cel filtering aid. After dilution of the filtrate with 10 mL of pentane, removal of the liquid amide(s) was accomplished by washing the filtrate with 10% (w/v) aqueous NaCl (4 15 mL portions). The organic layer was subsequently dried over anhydrous MgSO4, filtered, and the volatile organic solvents were removed by evaporation at reduced pressure. |
93% | With sodium tetrahydroborate; copper(ll) sulfate pentahydrate; cobalt(II) chloride hexahydrate In methanol at 20℃; for 0.333333h; | General hydrogenation procedure General procedure: The catalyst precursor in form of a 0.04 M CuSO4 and 0.004 M CoCl2 solution was added to a solution of the alkene/alkyne compound in methanol. The reaction was started by adding an initial portion of NaBH4, resulting in a color change to black (in situ prepared catalyst) and vigorous gas evolution. Additional portions of NaBH4 were added in intervals of typically three or four minutes. The reaction itself was carried out at room temperature and normal atmosphere. However, generation of heat due to the exothermic character of the reaction usually heated the reaction mixture to 30-40 °C. Cooling is generally not necessary in small scale. For large scale reactions a reflux condenser was used. The higher reaction temperature did not influence the reaction yield. The reaction mixture was finally quenched by adding 2 M H2SO4. Work up was carried out by extracting the water/methanol phase with DCM. The catalyst in general stays within the water/methanol layer. Drying the DCM layer with MgSO4 followed by filtration removes all remaining catalyst particles. The drying agent was filtered of and the DCM was removed in vacuo. |
With ethanol; hydrogen; platinum Hydrogenation; | ||
With water; triisobutylaluminum 1.) (CH2Cl)2, 0 deg C, 9h; Yield given. Multistep reaction; | ||
With water; dichloroaluminum hydride 1) ether, RT; Yield given. Multistep reaction; | ||
69 % Chromat. | With hydrogen In tetrahydrofuran at 20℃; for 5h; | |
With lumiflavin; N,N'-(2,6-pyridinediyl)bis(acetamide); hydrazine hydrate In chloroform at 30℃; Under air; | ||
With sodium tetrahydroborate In methanol at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium at 180℃; different temperature, catalyst concentration; study of polyhydroxyethylation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In dichloromethane for 6h; | |
94% | In dichloromethane for 0.5h; Ambient temperature; | |
84% | 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). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With hydrogen In para-xylene at 140℃; for 24h; Glovebox; Sealed tube; chemoselective reaction; | |
61.3% | With sulfurous dibromide In benzene | 2 EXAMPLE 2 (Process B) EXAMPLE 2 (Process B) Six milliliters (78 millimoles) of thionyl bromide are added to 20 ml of a solution of 5.36 g (32 millimoles) of tricyclo [4.3.1.12,5 ] undecane-1-ol in dry benzene and the entirety is refluxed for 1.5 hours. The reaction mixture is concentrated under reduced pressure and there is further added 20 ml of dry benzene. Reduced pressure concentration is repeated to distill out the excess thionyl chloride completely. The residue is distilled under reduced pressure to collect a fraction boiling at 96°-8° C./2mmHg. Thus 4.53 g (yield 61.3%) of 1-bromotricyclo [4.3.1.12,5 ] undecane are obtained. After cooling, colorless crystals having a melting point of 57.7°-58.5° C. are obtained. |
With hydrogen at 326.9℃; 1.5E5 Pa; Yield given; |
Multi-step reaction with 2 steps 1: red phosphorus; iodine 2: alcohol; aluminium-amalgam |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With oxygen; acetic acid;N-hydroxyphthalimide; at 100℃; under 760.051 Torr; for 4h; | EXAMPLE 23 In 3 mL of acetic acid was dissolved 375 mg of 1-undecanol to give a solution, and the solution was combined with 150 mg of the catalyst B10 obtained from Example 22 and 32 mg of N-hydroxyphthalimide, followed by stirring at 100C in an oxygen atmosphere at normal atmospheric pressure for 4 hours. The reaction mixture was analyzed through gas chromatography to find that undecanoic acid was produced in a yield of 22% with a conversion from 1-undecanol of 44%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium bromate; sulfuric acid; sodium bromide In water at 20℃; for 24h; | General procedure for octyl octanoate (2a) General procedure: A total of 1.0 g of 1-octanol (7.69 mmol) was taken in a 50-mL round-bottomed flask, to it NaBr 0.523 g (0.66 eq.), NaBrO 3 0.383 g (0.33 eq.), and 10 mL of H 2 O [comprises the bromide and bromate in 2:1 molar ratio] were added[6f]. The reaction mixture was stirred vigorously to dissolve the contents completely. To the above reaction mixture, the aqueous H 2 SO 4 solution (0.5 eq.) was added slowly under stirring over a period of 2.5 h at room temperature (prepared by adding 0.21 mL of 98% H 2 SO 4 to 1 mL of water). The reaction mixture was allowed to stir for up to 24 h. After the completion of reaction, the product was extracted with CH 2 Cl 2 (3 15 mL), the organic layer was dried with Na 2 SO 4 and removal of the solvent obtained octyloctanoate in 98% yield (0.953 g) as colorless liquid. The product was confirmed by GC-MS as well as by NMR. |
92% | With sodium bromite In water; acetic acid for 12h; Ambient temperature; | |
76% | With [RuCl2(p-cymene)(iPr2-imy)]; potassium hydroxide; tricyclohexylphosphine In 1,3,5-trimethyl-benzene at 163℃; for 18h; Inert atmosphere; |
99 %Chromat. | With cerium (IV) sulfate tetrahydrate; lithium bromide In water at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium tetrahydroborate In hexane; toluene at 100℃; | |
52% | With sodium tetrahydroborate In diethylene glycol dimethyl ether at 25℃; electrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetone Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In tetrahydrofuran at -15 - 15℃; | |
With triethylamine In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With pyridine In chloroform at 20℃; | |
68% | Stage #1: undecyl alcohol With sodium hydroxide In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: p-toluenesulfonyl chloride In tetrahydrofuran at 0 - 20℃; for 16h; Heating; | 1 To a stirred solution of undecan-1-ol 1 (2.0 g, 11.6 mmol) in THF (20 mL) was added NaOH (0.93 g, 23.2 mmol) at 0 °C. The mixture was stirred at room temperature for 15 min. Then cooled to 0 °C, p-toluene sulfonyl chloride (2.65 g, 13.92 mmol) was added to the reaction mixture and stirred at room temperature for 16 h. After consumption of starting material, the mixture was diluted with ethyl acetate (150 mL) and washed with ice cold water (2 x 20 mL), brine solution (20 mL), dried over sodium sulfate and concentrated. Crude compound was purified by 100-200 mesh silica gel column chromatography by eluting with 20 % ethyl acetate in hexanes to afford Undecyl 4- methylbenzenesulfonate 2 (2.6 g, 7.97 mmol, 68 % yield) as an off white solid. TLC system: 10 % Methanol in dichloromethane - Rf: 0.70; LCMS: m/z = 325.56 (M-H) - |
68% | Stage #1: undecyl alcohol With sodium hydroxide In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: p-toluenesulfonyl chloride In tetrahydrofuran at 20℃; for 16h; | 1 To a stirred solution of undecan-1-ol 1 (2.0 g, 11.6 mmol) in THF (20 mL) was added NaOH (0.93 g, 23.2 mmol) at 0 °C. The mixture was stirred at room temperature for 15 min. Then cooled to 0 °C, p-toluene sulfonyl chloride (2.65 g, 13.92 mmol) was added to the reaction mixture and stirred at room temperature for 16 h. After consumption of starting material, the mixture was diluted with ethyl acetate (150 mL) and washed with ice cold water (2 x 20 mL), brine solution (20 mL), dried over sodium sulfate and concentrated. Crude compound was purified by 100-200 mesh silica gel column chromatography by eluting with 20 % ethyl acetate in hexanes to afford Undecyl 4-methylbenzenesulfonate 2 (2.6 g, 7.97 mmol, 68 % yield) as an off white solid. TLC system: 10 % Methanol in dichloromethane - Rf: 0.70; LCMS: m/z = 325.56 (M-H) - |
With pyridine at 10 - 20℃; for 3h; | 4.2.1. General procedure for preparation of alkyl 4-methylbenzenesulphonates General procedure: 4-Methylbenzenesulphonyl chloride (55 mmol) was added slowly to a mixture of a primary alcohol (50 mmol) and 20 ml of pyridine at 10 °C. The reaction mixture was stirred for 3 h at 20 °C. After that 120 ml of 25 % hydrochloric acid was slowly added. The reaction mixture was then extracted with chloroform, organic layer dried with Na2SO4 and evaporated to yield alkyl 4-methylbenzenesulphonate as colourless oily liquid or white solid, which was used without further purification. Ethyl 4-methylbenzenesulphonate was purchased from Fluka. | |
With potassium hydroxide In tetrahydrofuran at 0 - 40℃; for 4h; | 1.2.1 Example 2: 1. Put undecyl alcohol (207mL, 1.0mol),P-toluenesulfonyl chloride (210g, 1.5mol),Tetrahydrofuran (850ml) is mixed in a 2 liter reaction flask,Cool down to 0 in ice water bath,Slowly add KOH (224g, 4.0mol) under mechanical stirring,Move the reaction flask to an oil bath at 40°C,Continue to stir for about 4 hours and stop the reaction.Distill the tetrahydrofuran in the system from the system,Then a milky white (with very light yellow) solid was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen; sodium methylate In tetrahydrofuran at 100℃; for 2.5h; Title compound not separated from byproducts.; | ||
1: 90 %Chromat. 2: 6 %Chromat. | With RuCl2(PNHNHP); potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 2h; Inert atmosphere; Autoclave; chemoselective reaction; | 7 Example 7 The reaction is carried out as described in Example 6 but with RuCl2(PNHNHP) catalyst 4b. After 2 hours GC-analysis revealed 4% substrate la, 90% 10-undecenol 2a, 6% undecanol 2b and 1% methyl undec-10-enoate 1a. CO/DB selectivity: 94:6. |
With OsHCl(CO)[(iPr)2PNH(CH2)2NHCH2Py]; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 100℃; for 2.5h; Autoclave; regioselective reaction; | 15 EXAMPLE 15. TYPICAL PROCEDURE FOR HYDROGENATION OF ESTERS USINGCOMPLEXES (la), AND (3).A solution of catalyst 1 (5.2 mg/mL) and a base (0.2 mmol) in THF was mixed with 0.02 mol of the ester substrate in 6 mL of THF. The mixture was then transferred into a 75 mL stainless-steel reactor (Parr 4740) equipped with a magnetic stir bar. The reactor was purged by two cycles of pressurization/venting with H2 (150 psi, 10 Bar), pressurized with H2 (725 psi, 50 Bar), and was disconnected from the H2 source. The hydrogenation was conducted at 40-100 °C. At the end of the required reaction time, the reactor was placed into a cold-water bath and depressurized afier cooling to the ambient temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;tributylphosphine; cobalt(II) decanoate; In n-heptane; at 170℃; under 63756.4 Torr; for 48h;Conversion of starting material; | Co(II)-decanoate (1.2% Co in heptane) (2.5 ml, 0.36 mmol), heptane (7 ml), C10-C15 olefins/C10-C15 paraffins (20 ml, pre-mixed each 8.3% by volume as described above) and nBu3P (1.44 mmol) were placed in a 50 ml autoclave, degassed with argon and heated to 170 C. Syngas (H2:CO 2:1) was added to 85 bar and supplied at this pressure for 48 h.Using an Agilent Pona GC-column (50 m×0.20 mm×0.50 musn, 40 C. for 5 minutes, 10 C./minute to 300 C., 300 C. for 20 minutes) which separates mainly on differential boiling points, the reaction mixture containing the C11-C16 alcohols and C10-C15 paraffins, was injected and the GC trace indicated that tridecane, tetradecane and pentadecane overlap with the resulting alcohols indicating that it would not be possible to separate all the paraffins via fractional distillation from the alcohol products (see FIG. 5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With [((Me)NN2)NiCl] In tetrahydrofuran; ISOPROPYLAMIDE at -35 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24.0% | (iii) General procedure for the synthesis of phosphate triester derivatives of FLC (2a-h); 2-Cyanoethyl N, N-DIISOPROPYLCHLOROPHOSPHORAMIDITE (267, UL, 1.2 mmol) (for 2a-e) or METHYL N, N-DIISOPROPYLCHLOROPHOSPHORAMIDITE (240 PL, 1. 2 m mol) (for 2f-h) and diisopropyl ethylamine (209 P. L, 1.2 mmol) were added to a solution of alcohol (ROH) (1. OMMOL) INDRY DCM (2mL) under aN2 atmosphere. After stirring for20 hours, the reaction mixture was partitioned between EA (10 mL) and distilled water (10 mL). The organic layer was then washed with brine (10 mL) and dried over anhydrous MGS04. The solvent was removed in vacuo and the syrup was dried under vacuum overnight. FLC (200 mg, 0.6 mmol) and 1H-tetrazole (84 mg, 1.2 mmol) were dissolved in dry dichloromethane (DCM, 2 mL) under a N2 atmosphere. The syrup was dissolved in dry DCM (1 mL) and was added to this reaction mixture. After stirring for 3 hours, the reaction was cooled to 0 C and t-butyl hydroperoxide (0.3 mL) was added. After stirring for 1 hour, the reaction mixture was partitioned between EA (10 mL) and distilled water (10 mL). The organic phase was then washed with brine (10 mL) and dried over anhydrous MgSO4. The solvent was removed in vacuo. The syrup residue was purified by silica gel column chromatography, eluting with hexane and acetone from 3: 1 (v/v) to 1: 1 (v/v) to yield 2a-h (Scheme 3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | With mer-[RuCl3(1,4-bis(diphenylphosphino)butane)(4-phenylpyridine)]; hydrogen In tetrahydrofuran at 160℃; for 24h; | synthesis of alcohol Complexes (1) and (4) were the most active complexes, whichgave 32% of maximal conversion, with TOF average of 6.2 h-1. Itcan be observed in Table 1 that the main product is the isomer-ized olefins in all reactions. The formation of desired products(1d + 1e) was 6% (isolated yield) in the best case, using (3) and (4) aspre-catalysts with a syngas pressure of 40 bar. Table 1 shows thatby increasing the syngas pressure from 20 to 40 bar, the desiredproduct (1d + 1e) also increases, but not as significantly, thereforeadditional catalytic experiments were conducted to improve theconversion and product yields. |
90.1 %Chromat. | With (acetylacetonato)dicarbonylrhodium (l); Shvo's catalyst; hydrogen; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl acetamide at 120℃; for 12.5h; Autoclave; | |
With dicarbonyl(acetylacotonato)rhodium(I); 6-[bis(4-fluorophenyl)phosphanyl]-1H-pyridin-2-one; N-(5-bis(4-methoxyphenyl)phosphanylpyrrol-2-carbonyl)guanidine; hydrogen In toluene at 80℃; for 24h; Inert atmosphere; Autoclave; regioselective reaction; |
90 %Chromat. | With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); dicarbonylacetylacetonato rhodium (I); hydrogen; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl acetamide at 120℃; for 12.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With hydrogenchloride In 1,4-dioxane at 45℃; for 4h; Inert atmosphere; | 8 Example 8 Undecyl (4S)-3-oxo-8-[2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetate hydrochloride 704 mg (1.24 mmol) of (4S)-3-oxo-8-[2-(8-tert-butoxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetic acid obtained in Example 5-(a) and 1.30 mL (6.26 mmol) of 1-undecyl alcohol were mixed, 12.4 mL (49.6 mmol) of 4N hydrogen chloride/1,4-dioxane solution was added to the mixture, and the resulting mixture was stirred under nitrogen gas atmosphere at 45°C for 4 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, the residue was applied to silica gel column chromatography (eluent; ethyl acetate→chloroform:methanol=19:1 (V/V)), and the separated fractions containing the desired product were concentrated under reduced pressure to obtain 527 mg of the title compound as pale yellow foam. (Yield 65%) Mass spectrum (FAB, m/z): 621 (M++1) 1H-NMR spectrum (DMSO-d6, δ ppm): 0.85 (t, J=6.7Hz, 3H), 1.21-1.31 (m, 16H), 1.50-1.58 (m, 2H), 1.94-2.02 (m, 2H), 2.63-2.76 (m, 2H), 2.89 (t, J=6.3Hz, 2H), 3.01 (dd, J1=17.3Hz, J2=3.7Hz, 1H), 3.78-3.89 (m, 3H), 3.99 (t, J=6.5Hz, 2H), 4.11-4.28 (m, 5H), 5.31 (d, J=16.6Hz, 1H), 6.80-6.85 (m, 3H), 7.04 (d, J=9.5Hz, 1H), 8.22 (brs, 1H), 12.29 (brs, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Inert atmosphere; | 4.1.2. General procedure for preparation alkyl-6-(2,5-dioxopyrrolidin-1-yl)hexanoates (2a-g) General procedure: A mixture of organic acid 1 (4.69 mmol), N,N'-dicyclohexylcarbodiimide (5.16 mmol), appropriate primary alcohol (9.38 mmol) and a catalytic amount of 4-(dimethylamino)pyridine (0.47 mmol) in dry dichloromethane (15 mL) was stirred at room temperature under a nitrogen atmosphere overnight. The resulting precipitate of N,N'-dicyclohexylurea was filtered off. The filtrate was evaporated and the residue was purified by column chromatography on silica gel using ethyl acetate/petroleum ether (1:2) as the eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With hydrogenchloride In 1,4-dioxane; water at 45℃; for 4h; Inert atmosphere; | 8 Example 8 Undecyl (4S)-3-oxo-8-[2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetate hydrochloride 704 mg (1.24 mmol) of (4S)-3-oxo-8-[2-(8-tert-butoxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidin-2-yl)ethoxyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetic acid obtained in Example 5-(a) and 1.30 mL (6.26 mmol) of 1-undecyl alcohol were mixed, 12.4 mL (49.6 mmol) of 4N hydrogen chloride/1,4-dioxane solution was added to the mixture, and the resulting mixture was stirred under nitrogen gas atmosphere at 45°C for 4 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was applied to silica gel column chromatography (eluent; ethyl acetate→chloroform:methanol=19:1 (V/V)), and the separated fractions containing the objective material were concentrated under reduced pressure to obtain 527 mg of the title compound as pale yellow foam. (Yield: 65%) Mass Spectrum (FAB, m/z): 621 (M++1) 1H-NMR Spectrum (DMSO-d6, δ ppm): 0.85 (t, J=6.7Hz, 3H), 1.21-1.31 (m, 16H), 1.50-1.58 (m, 2H), 1.94-2.02 (m, 2H), 2.63-2.76 (m, 2H), 2.89 (t, J=6.3Hz, 2H), 3.01 (dd, J1=17.3Hz, J2=3.7Hz, 1H), 3.78-3.89 (m, 3H), 3.99 (t, J=6.5Hz, 2H), 4.11-4.28 (m, 5H), 5.31 (d, J=16.6Hz, 1H), 6.80-6.85 (m, 3H), 7.04 (d, J=9.5Hz, 1H), 8.22 (brs, 1H), 12.29 (brs, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In water at 267℃; for 0.00805556h; Autoclave; Microwave irradiation; Industry scale; | 5 Example 5Production of Undecyl 2-HydroxypropanoateIn a 10 l Büchi stirred autoclave with stirrer, internal thermometer and pressure equalizer, 2.25 kg of lactic acid (as 90% strength aqueous solution, 22.5 mol) were introduced as initial charge and admixed with 7.75 kg of undecyl alcohol (Exxal 11 from Exxon, 45 mol) and 0.075 kg of methanesulfonic acid.The mixture obtained in this way was pumped continuously through the reaction tube at 6 l/h at an operating pressure of 25 bar and exposed to a microwave power of 3.7 kW, 92% of which was absorbed by the reaction material. The residence time of the reaction mixture in the irradiation zone was ca. 29 seconds. At the end of the reaction tube, the reaction mixture had a temperature of 267° C. The reaction mixture was cooled to room temperature directly after leaving the reactor using a high-intensity heat exchanger.A conversion of 89% of theory was achieved. The reaction product was colorless. Following neutralization of the catalyst with hydrogencarbonate solution and distillative removal of water of reaction and unreacted starting materials, 4.7 kg of undecyl lactate with a purity of >98.5% were obtained after vacuum distillation at 1 mbar and 170° C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: undecyl alcohol; (6-((4-(pyrazol-1-yl)benzyl)(pyridin-3-ylsulfonyl)aminomethyl)pyridin-2-ylamino)acetic acid With hydrogenchloride In 1,4-dioxane at 20℃; for 15h; Stage #2: With sodium hydrogencarbonate In water | 13 [Example 13] Undecyl (6-{(pyridin-2-ylsulfonyl)[4-(thiazol-2-yl)benzyl]aminomethyl}pyridin-2-yl-amino)acetate hydrochloride To 110 mg (0.222 mmol) of (6-{(pyridin-2-ylsulfonyl)[4-(thiazol-2-yl)benzyl]-aminomethyl}pyridin-2-ylamino)acetic acid obtained by the same manner as in Reference example 3-(b) were added 0.83 ml (3.3 mmol) of 4N hydrogen chloride/1,4-dioxane solution and 0.83 ml (4.0 mmol) of 1-undecanol, and the mixture was stirred at room temperature for 15 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was applied to silica gel column chromatography (eluent; n-hexane:ethyl acetate=3:1→1:1 (V/V)), the fractions containing the objective material were concentrated under reduced pressure. The obtained residue was dissolved in 5 ml of diethyl ether, 0.5 ml of a diethyl ether solution saturated with hydrogen chloride was added to the mixture, and the mixture was concentrated under reduced pressure to obtain 118 mg of the title compound as white solid. (Yield: 74% as dihydrochloride) Mass spectrum (FAB, m/z): 650 (M++1). 1H-NMR spectrum (DMSO-d6, δ ppm): 8.71 (d, J=4.4 Hz, 1H), 8.04 (dd, J=6.7, 6.7 Hz, 1H), 7.94-7.89 (m, 2H), 7.84-7.79 (m, 2H), 7.79 (d, J=3.1 Hz, 1H), 7.67 (dd, J=6.7, 4.4 Hz, 1H), 7.50 (brs, 1H), 7.36-7.31 (m, 2H), 6.62 (brs, 1H), 6.52 (brs, 1H), 4.65 (s, 2H), 4.51 (brs, 2H), 4.14-3.97 (m, 4H), 1.55-1.46 (m, 2H), 1.29-1.06 (m, 16H), 0.84 (t, J=7.0 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 77% 2: 10% | With sodium tetrahydroborate; ruthenium(III) trichloride hydrate In N-Methylformamide; N,N-dimethyl acetamide; water at 0℃; for 1h; chemoselective reaction; | General procedure for alkene reduction General procedure: To a 15-mL 1-neck reaction flask fitted with a glass stopper [Note: A larger-scale reaction may require the use of a pressure vessel and/or addition of NaBH4 in small portions.] were added a small spin bar, 0.18-0.20 mmol of substrate, 0.60 mL of 5:1 (v/v) [10:1 (v/v) in Table 1, entry 3] liquid amide(s)/H2O, and 7.0 mg (0.034 mmol) of ruthenium(III) chloride hydrate (Sigma-Aldrich Catalog No. 206229). After cooling the latter mixture to 0 C (external ice-H2O bath), 9.0 mg (0.24 mmol) of NaBH4 powder was added in one portion; and the mixture was subsequently stirred at 0 C for 60 min. The reaction was then quenched by addition of 2.0 mL of 2 M aqueous HCl to the reaction flask, followed by 1.0 mL of pentane and subsequent stirring of the mixture at 0 C for 15 min. The product was then isolated by dilution of the reaction mixture with 10 mL of 4:1 (v/v) pentane/dichloromethane; and solid material was removed by filtration through a small pad of Hyflo Super-Cel filtering aid. After dilution of the filtrate with 10 mL of pentane, removal of the liquid amide(s) was accomplished by washing the filtrate with 10% (w/v) aqueous NaCl (4 15 mL portions). The organic layer was subsequently dried over anhydrous MgSO4, filtered, and the volatile organic solvents were removed by evaporation at reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 83% 2: 6 %Chromat. | With dodecacarbonyl-triangulo-triruthenium; 2-(dicyclohexylphosphino)-1-methyl-1H-imidazole; water; hydrogen; lithium chloride In 1-methyl-pyrrolidin-2-one at 130℃; for 20h; Autoclave; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: undecyl alcohol; 1-Decanol; 2-hydroxy 4-methylthiobutyric acid; nonyl alcohol at 110℃; for 2h; Inert atmosphere; Stage #2: With dihydrogen peroxide In water; ethyl acetate at 20℃; Cooling with ice; | 16 Example 16: Preparation of Oligomeric Mixture Obtained from Oxidation of the Condensation Products of -9 To 2-hydroxy-4-(methylthio)butanoic acid (Alimet, 88%) (5.09g, 29.8mmol) in a 20 ml vial was added NEODOL-9 (3.4 g, 23.5 mmol) and Amberlyst 15 (0.53 g). The resulting mixture was heated at 1 10°C while bubbling a stream of nitrogen through it for 2 hrs. The reaction was cooled to room temperature, diluted with ethyl acetate (25 ml_) and then filtered. The filtrate was cooled on an ice bath and then treated with hydrogen peroxide (30%, 6.1 ml, 59.6 mmol). The reaction was stirred for 30 min and then the ice bath was removed and stirring continued overnight at room temperature. The reaction was washed with 30 ml_ water plus 10 ml_ of brine, 10% sodium bisulfite (1 x40 ml), sat. sodium bicarbonate (2x40 ml_) and then water (2x20 ml_). The organic layer was separated and evaporated to give the monomer, dimer and oligomer mixture as a light yellow oil (6.43 g, 82%). k= 0, m/z 293 (MH+), k = 1 , m/z 441 (MH+), k = 2, m/z 589 (MH+), k = 0 C10, m/z 307 (MH+), k = 0 C1 1 , m/z 321 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: cyclododecanone With maleic anhydride; dihydrogen peroxide In water at 46 - 49℃; for 22h; Stage #2: With hydrogen In methanol; water at 200℃; for 24h; Autoclave; Inert atmosphere; | 9 Example 9: Reduction of crude BV product in water and methanol at 2000psig [00129] A mixture of 64.1 crude BV product, 24 g methanol, 32 g water, 22 g water and 5 g of 2% Ru on carbon catalyst containing 6% Re and 0.9% Sn were charged to a 300 mL Stainless Steel autoclave containing a thermocouple, cooling coil, baffle and stirrer. The BV product contained 39.4 wt% maleic acid, 29.3 wt% LLON, 1.9 wt% 12-hydroxydodecanoic acid, 3.5 wt% 1,12-dodecanedioic acid, 3.4 wt% mono methyl ester of 1,12-dodecandioic acid, and 12.5 wt% water. The vessel was flushed first with nitrogen followed by hydrogen, and pressurized to 2000psig with hydrogen. Stirring at 1800 rpm was commenced and the reactor was heated to 200°C. The hydrogenation was run for 24 hr. Analysis of the product showed a combined 99.8 wt% conversion of LLON, DDDA and HDDA with 88.8% molar selectivity to C12LD. Also produced was 1-undecanol (6.4 molar%) along with 12- hydroxydodecanoic acid (1.2 molar%) and methyl 12-hydroxydodecanoate (4.9 molar%). The ratio of hydrogenolysis products to C12LD was 0.099. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15.9%; 27.6% | With hydrogen; In ethanol; water; at 230℃; under 25066.7 Torr; | For a hydrodeoxygenation catalyst, 1.5 g of 1% Pt on SiAl was loaded on a one-quarter inch stainless steel tube reactor and heated from room temperature to 450 C. over 8 hours under 25 mL/min (GHSV of ?500 hr-1) of flowing hydrogen gas at atmospheric pressure. At a liquid flow rate of 0.02 mL/minute (LHSV?0.4 hr-1), temperature of 230 C., and pressure of 470 psig of hydrogen, a spontaneously separating organic phase containing ethyl undecanoate was collected. GCMS analysis of the organic phase revealed the organic composition contained the following components (GCMS area %): decane (0.6%), undecane (2.7%), undecanol (15.9%), decane ethyl ester (3.9%), undecanoic ethyl ester (27.6%), and some unidentified peaks (22.7%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 87 %Chromat. 2: 9 %Chromat. | With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 4h; Inert atmosphere; Autoclave; Sonication; chemoselective reaction; | 1 Example 1 Under argon, toluene (3 ml) is added to a glass vial (50 ml) containing RuCI2(PNNP) catalyst 4a (2.5 mg, 0.01 mol%) and NaOMe (0.163 g, 3 mmol). The suspension is treated in an ultrasonic bath until a reddish solution is obtained (3-5 min) to which a solution of ethyl 10-undecenoate (6.4 g, 29 mmol) in toluene (18 ml) is added. The vial is capped (crimp cap & silicone septum), punctured with a needle and put in a Parr autoclave. While stirring with a magnetic stirrer the autoclave is flushed three times with hydrogen, then put under hydrogen pressure (40 bar) and heated to 100 °C. After 4 hours the heating is stopped and the pressure released. To the colourless reaction mixture is added 2% H3P04 (4 ml) and diethyl ether (10 ml). The organic phase is washed with brine, dried over MgS04 and concentrated in vacuo. GC-MS analysis revealed 3% substrate 1b, 87% 10-undecenol 2a, 9% undecanol 2b, and 1% transesterification product 3. CO/DB selectivity: 91:9. The analytical data of ethyl undec-10-enoate 1b, 10-undecenol 2a and undecanol 2b were identical with the ones from commercial samples of these compounds. |
With OsHCl(CO)[(iPr)2PNH(CH2)2NHCH2Py]; hydrogen; sodium ethanolate In tetrahydrofuran at 80℃; for 2.5h; Autoclave; regioselective reaction; | 15 EXAMPLE 15. TYPICAL PROCEDURE FOR HYDROGENATION OF ESTERS USINGCOMPLEXES (la), AND (3).A solution of catalyst 1 (5.2 mg/mL) and a base (0.2 mmol) in THF was mixed with 0.02 mol of the ester substrate in 6 mL of THF. The mixture was then transferred into a 75 mL stainless-steel reactor (Parr 4740) equipped with a magnetic stir bar. The reactor was purged by two cycles of pressurization/venting with H2 (150 psi, 10 Bar), pressurized with H2 (725 psi, 50 Bar), and was disconnected from the H2 source. The hydrogenation was conducted at 40-100 °C. At the end of the required reaction time, the reactor was placed into a cold-water bath and depressurized afier cooling to the ambient temperature. | |
1: 94 %Chromat. 2: 6 %Chromat. | With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 5h; Inert atmosphere; Autoclave; | 5 EXAMPLE 5 Under argon, RuCl2(PNNP) catalyst 4a (3.7 mg, 50 ppm) in distilled and degassed THF (5 ml) is treated for 5 min with ultrasound to give a fine suspension which is added to a suspension of KOMe_(0.63 g, 9 mmol) in ethyl 10-undecenoate 1b (19.2 g, 90 mmol) and distilled and degassed THF (58 ml) in a 120 ml Premex autoclave under argon. The autoclave is flushed three times with hydrogen and then heated at 100° C. under 50 bar hydrogen and 1200 rpm with overhead stirring. After 5 hours the heating is stopped, the pressure released and the content of the autoclave poured onto 2% H3PO4 (10 ml). After phase separation the organic phase is washed with water (2×30 ml), dried over MgSO4, filtered and evaporated. GC-analysis of the quantitatively obtained material revealed 94% 10-undecenol 2a and 6% undecanol 2b. |
With C30H34Cl2N2P2Ru; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 5h; Glovebox; Autoclave; | 28 Example 28: Chemoselective hydrogenation of ester compounds catalyzed by ruthenium complex Ia General procedure: In a glove box, add a ruthenium complex Ia (0.7 mg, 0.001 mmol),Potassium methoxide (35-175 mg, 0.5-2.5 mmol), tetrahydrofuran (5-20 mL), and ester compounds (10-50 mmol).After sealing the autoclave, take it out of the glove box and fill it with 50atm of hydrogen.The reaction kettle was heated and stirred in an oil bath at 100 ° C for 10 to 24 hours.After the reaction kettle was cooled in an ice-water bath for 1.5 hours, the excess hydrogen was slowly released.The solvent was removed from the reaction solution under reduced pressure, and the residue was purified with a short silica gel column to obtain an alcohol compound. The results are shown in Table 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 54 %Chromat. 2: 15 %Chromat. 3: 8 %Chromat. | With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 3h; Inert atmosphere; Autoclave; chemoselective reaction; | 3 Example 3 The reaction was carried out as described in Example 1 but with methyl undecenoate la and 0.05% RuCI2(PNNP) catalyst 4a. After 3 h a 87% conversion to 10-undecenol 2a (54%), 9-undecenol 2d (8%), undecanol 2b (15%), methyl undecanoate 2c (3%) and transesterification products 3 (7%) was detected by GC. The CO/terminal double bond (DB) selectivity was 68:32. The analytical data of 10-undecenol 2a, undecanol 2b and methyl undecanoate 2c are identical with the ones obtained from commercial samples of these compounds. The analytical data of 9-undecenol 2d (partially in J.Organomet.Chem.691, 5278, 2006 and references) and undecenoic acid undecenyl ester 3 (Tetrahedron 63, 11325, 2007) were identical with the ones described in the literature. MS of 2d: 152 (5%, [M-18]+), 124 (7%), 123 (8%), 110 (11%), 109 (14%), 96 (29%), 95 (30%), 82 (44%), 81 (49%), 68 (49%), 67 (54%), 55 (100%), 54 (36%), 41 (43%). |
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 3h; Inert atmosphere; Autoclave; chemoselective reaction; | 3 EXAMPLE 3 The reaction was carried out as described in Example 1 but with methyl undecenoate 1a and 0.05% RuCl2(PNNP) catalyst 4a. After 3 h a 87% conversion to 10-undecenol 2a (54%), 9-undecenol 2d (8%), undecanol 2b (15%), methyl undecanoate 2c (3%) and transesterification products 3 (7%) was detected by GC. The CO/terminal double bond (DB) selectivity was 68:32 The analytical data of 10-undecenol 2a, undecanol 2b and methyl undecanoate 2c are identical with the ones obtained from commercial samples of these compounds. The analytical data of 9-undecenol 2d (partially in J. Organomet. Chem. 691, 5278, 2006 and references) and undecenoic acid undecenyl ester 3 (Tetrahedron 63, 11325, 2007) were identical with the ones described in the literature. MS of 2d: 152 (5%, [M-18]+), 124 (7%), 123 (8%), 110 (11%), 109 (14%), 96 (29%), 95 (30%), 82 (44%), 81 (49%), 68 (49%), 67 (54%), 55 (100%), 54 (36%), 41 (43%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.56% | With toluene-4-sulfonic acid In toluene Reflux; | 28.1 Synthesis of undecyl 2-aminopropanoate (82) Synthesis of undecyl 2-aminopropanoate (82) To a stirred solution of DL-alanine 1 (15 g, 168.5 mmol) in toluene (300 mL) was added 1-undecanol 81 (26.22 g, 151.68 mmol) in one lot, followed by pTSA (35.38 g, 185.35 mmol). After the addition, the temperature of the reaction mixture was slowly raised to reflux temperature, the water was separated azeotropically and the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum, the obtained residue was taken in ethyl acetate (200 mL) and washed with aqueous 5% Na2CO3 (3*50 mL) followed by brine solution. The organic layer was dried over Na2SO4 and concentrated under vacuum to afford 82 (40 g, yield: 97.56%) as a liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With C32H34BrN5ORu; potassium methanolate; hydrogen In tetrahydrofuran at 70℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With β-cyclodextrin-SO3H In neat (no solvent) at 70℃; for 3h; | |
98% | With Glu-Fe3O4-SO3H at 20℃; for 2.5h; | Procedure for Esterification General procedure: 1 mmol of acid, 3 mmol of alcohol and Glu-Fe3O4-SO3H catalyst were stirred together at rt for required time. The reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with DCM and the catalyst separated using external magnetic field. DCM layer was then concentrated, loaded on silica gel and purified by column chromatography to obtain pure ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 20h; Inert atmosphere; Autoclave; Overall yield = 15.6 g; | 4 EXAMPLE 4 Under argon, RuCl2(PNNP) catalyst 4a (7.5 mg, 0.01 mol %) in toluene (5 ml) are treated 5 min with ultrasound to give a fine suspension which is added to a suspension of ethyl 10-undecenoate 1b (19.2 g, 90 mmol) and NaOMe (0.5 g, 9 mmol) in toluene (16 ml) in a 120 ml Premex autoclave under argon. The autoclave is flushed three times with hydrogen and then heated at 100° C. under 50 bar hydrogen and 1200 rpm with overhead stirring. After 6 hours the GC-analysis revealed 6% substrate 1b, 90% 10-undecenol 2a, 4% undecanol 2b. CO/DB selectivity: 96:4. After 20 h the autoclave is cooled, the pressure released and the content of the autoclave poured onto 2% H3PO4 (10 ml). After phase separation the organic phase is washed with water (2×30 ml), dried over MgSO4, filtered and evaporated. The residue of 15.6 g consisted of 80% 10-undecenol 2a, 15% undecanol 2b and 5% isomer 2d according to GCMS and NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With SiO2 supported phosphomolybdic acid at 90℃; for 6h; Sealed tube; | 15 2.4. General experimental procedure for microwave-assisted glycosylation General procedure: d-Xylose (or d-lyxose) (1.0g, 6.66mmol, 1 equiv), PMoA/SiO2 (1g, 0.06mmol, based on PMoA) and 5 equiv of corresponding alcohol (C8-C14) were mixed to obtain reaction mixture. In the case of solid alcohol chloroform, (20ml) was used as solvent. The reaction mixture was heated in oil bath for an appropriate time (90°C, 4-8h). The composition of the reaction mixture was determined by 1H NMR spectroscopy. The reaction mixture was worked up in exactly the same way as mentioned in the previous experiment. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sulfonated graphene oxide In neat (no solvent) at 80℃; for 4h; Green chemistry; stereoselective reaction; | General procedure for glycosylation of protected sugars (Table 3, entries 1-3, 5, 6-8) General procedure: A mixture of protected sugars (1 mmol), alcohol (5 mmol), and 5 wt% sulfonated graphene oxidewas takenat rt and then stirred at 80°C for the required time.A small amount of reaction mixture was taken out at regular intervals using a micropipette and diluted with ethyl acetate, and the reaction progress was monitored by TLC. After consumption of all of the glycosyl donor, the reaction mixture was cooled to rt and diluted with ethyl acetate, and the catalyst was separated by filtration.The filtrate was concentrated at reduced pressure, and crude products were purified by column chromatography to remove the excess alcohol to obtain the desired glycoside. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen; triphenylphosphine In water at 80℃; for 3h; Autoclave; Inert atmosphere; regioselective reaction; | 2.1. The general procedure of hydroformylation General procedure: Hydroformylation experiments were carried out in 100 mL (or50 mL) stainless steel autoclaves provided with a manometer, a thermostat, a magnetic stirrer, and a gas inlet/outlet system. The catalyst, Rh(acac)(CO)2 or Rh/PAA, and PPh3 were placed in the autoclave. Then, 1.5 mL of substrate were introduced into the auto-clave under a nitrogen atmosphere. In the case of experiments carried out on water, 1.5 mL of twice distilled water was added. The autoclave was closed, flushed with hydrogen (5 bar) three times,and thereafter pressurized with a synthesis gas (H2: CO = 1:1) to 10 bar (or 14 bar) and heated to 80°C (or 60°C). After the reaction was finished, the autoclave was cooled to room temperature and the residual gases depressurized. The product mixture was immediately analyzed by NMR spectra, the catalyst was removedby StratospheresTMSpe, and the obtained products were identified by means GC and GC-MS.Selected reaction mixtures were analyzed additionally using1Hand13C NMR (Figs. 1-3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With Glu-Fe3O4-SO3H at 20℃; for 5h; | Procedure for Esterification General procedure: 1 mmol of acid, 3 mmol of alcohol and Glu-Fe3O4-SO3H catalyst were stirred together at rt for required time. The reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with DCM and the catalyst separated using external magnetic field. DCM layer was then concentrated, loaded on silica gel and purified by column chromatography to obtain pure ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 6.7% 2: 48.3% | With chloro(1,5-cyclooctadiene)(pentamethylcyclopentadiene)ruthenium(II); potassium <i>tert</i>-butylate; hydrogen; (2-aminoethyl)diphenylphosphane In tetrahydrofuran at 120℃; for 18h; Inert atmosphere; Autoclave; | 2 Three glass containers for catalyst preparation were prepared, Cp * Ru (cod) Cl (5.7 mg, 0.015 mmol)as transition metal compound for hydrogenation catalyst of selective hydrogenation reaction catalyst material, the compound A-46 (3.5 mg, 0.015 mmol) auxiliaries hydrogenation reaction catalyst, as a basic compound, potassium t-butoxide (1.7 mg, 0.015 mmol) were added. These were sequentially made into a glass container A (transition metal compound for hydrogenation catalyst), B (auxiliary agent) and C (basic compound). Separately, Rh (acac) (CO) 2 (5.2 mg, 0.020 mmol) was used as a rhodium compound for the hydroformylation reaction catalyst in a stainless steel autoclave having an internal volume of 50 ml containing a magnetic stirrer in a container and the bidentate organophosphorus compound L-22 (42.9 mg, 0.040 mmol) was weighed out as a ligand of the hydroformylation reaction catalyst. Next, 1, 4-dioxane (0.5 ml) was added as a solvent to each of the above-mentioned glass containers A, B, C under a nitrogen atmosphere to dissolve each component, and then the solution of the glass container A was charged into a glass transferred to a container B, after stirring at room temperature for 5 minutes, the solution in the glass container B was further transferred to a glass container C with a cannula and stirred for 5 minutes. In addition, 1, 4-dioxane (0.5 ml) as a solvent was added to the autoclave under a nitrogen atmosphere and stirred for 5 minutes. Subsequently, the solution of the glass container C was transferred to an autoclave with a cannula, the inside of the glass container C was washed with 1, 4-dioxane (2.0 ml), and the washing liquid was also transferred to the autoclave. Further, 448.9 mg (cis-2-decene: 2.0 mmol, 1 mol / mol) of a mixed solution of cis-2-decene (reaction raw material) and n-dodecane (internal standard substance for GC analysis) N-dodecane: 1.0 mmol) was added. After sealing the autoclave, quickly hydrogen from a gas supply valve/ carbon monoxide mixed gas (mixing ratio: 1/1) was introduced up to 0.5 Mpa, Under stirring at 800 rpm with a magnetic stirrer, reacted for 18 hours while heating at 120°C in an electric furnace (the amount of 1,4-dioxane used is 88% by weight based on the total weight of the reaction medium). After completion of the reaction, the reaction was cooled down to room temperature and the residual gas was released, and then the reaction results were analyzed by NMR and gas chromatography. As a result, undecanal yield was 4.0%, undecanol yield was 62.2%. In addition, the ratio (L / B ratio) of linear alcohol (1-undecanol) to branched alcohol (2-methyl-1-decanol etc.) in undecanol was 17 (linear selectivity = 94% |
1: 6.9% 2: 34.8% | With chloro(1,5-cyclooctadiene)(pentamethylcyclopentadiene)ruthenium(II); potassium <i>tert</i>-butylate; hydrogen; (2-aminoethyl)diphenylphosphane In toluene at 120℃; for 18h; Inert atmosphere; Autoclave; | 1 Three glass containers for catalyst preparation were prepared, Cp * Ru (cod) Cl (5.7 mg, 0.015 mmol)as transition metal compound for hydrogenation catalyst of selective hydrogenation reaction catalyst material, the compound A-46 (3.5 mg, 0.015 mmol) auxiliaries hydrogenation reaction catalyst, as a basic compound, potassium t-butoxide (1.7 mg, 0.015 mmol) were added. These were sequentially made into a glass container A (transition metal compound for hydrogenation catalyst), B (auxiliary agent) and C (basic compound). Separately, Rh (acac) (CO) 2 (5.2 mg, 0.020 mmol) was used as a rhodium compound for the hydroformylation reaction catalyst in a stainless steel autoclave having an internal volume of 50 ml containing a magnetic stirrer in a container and the bidentate organophosphorus compound L-22 (42.9 mg, 0.040 mmol) was weighed out as a ligand of the hydroformylation reaction catalyst. Next, 1, 4-dioxane (0.5 ml) was added as a solvent to each of the above-mentioned glass containers A, B, C under a nitrogen atmosphere to dissolve each component, and then the solution of the glass container A was charged into a glass transferred to a container B, after stirring at room temperature for 5 minutes, the solution in the glass container B was further transferred to a glass container C with a cannula and stirred for 5 minutes. In addition, 1, 4-dioxane (0.5 ml) as a solvent was added to the autoclave under a nitrogen atmosphere and stirred for 5 minutes. Subsequently, the solution of the glass container C was transferred to an autoclave with a cannula, the inside of the glass container C was washed with 1, 4-dioxane (2.0 ml), and the washing liquid was also transferred to the autoclave. Further, 448.9 mg (cis-2-decene: 2.0 mmol, 1 mol / mol) of a mixed solution of cis-2-decene (reaction raw material) and n-dodecane (internal standard substance for GC analysis) N-dodecane: 1.0 mmol) was added. After sealing the autoclave, quickly hydrogen from a gas supply valve/ carbon monoxide mixed gas (mixing ratio: 1/1) was introduced up to 0.5 Mpa, Under stirring at 800 rpm with a magnetic stirrer, reacted for 18 hours while heating at 120°C in an electric furnace (the amount of 1,4-dioxane used is 88% by weight based on the total weight of the reaction medium). After completion of the reaction, the reaction was cooled down to room temperature and the residual gas was released, and then the reaction results were analyzed by NMR and gas chromatography. As a result, undecanal yield was 4.0%, undecanol yield was 62.2%. In addition, the ratio (L / B ratio) of linear alcohol (1-undecanol) to branched alcohol (2-methyl-1-decanol etc.) in undecanol was 17 (linear selectivity = 94% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.2% | With chloro(1,5-cyclooctadiene)(pentamethylcyclopentadiene)ruthenium(II); potassium <i>tert</i>-butylate; hydrogen; (2-aminoethyl)diphenylphosphane In 1,4-dioxane at 120℃; for 18h; Inert atmosphere; Autoclave; | 1 Three glass containers for catalyst preparation were prepared, Cp * Ru (cod) Cl (5.7 mg, 0.015 mmol)as transition metal compound for hydrogenation catalyst of selective hydrogenation reaction catalyst material, the compound A-46 (3.5 mg, 0.015 mmol) auxiliaries hydrogenation reaction catalyst, as a basic compound, potassium t-butoxide (1.7 mg, 0.015 mmol) were added. These were sequentially made into a glass container A (transition metal compound for hydrogenation catalyst), B (auxiliary agent) and C (basic compound). Separately, Rh (acac) (CO) 2 (5.2 mg, 0.020 mmol) was used as a rhodium compound for the hydroformylation reaction catalyst in a stainless steel autoclave having an internal volume of 50 ml containing a magnetic stirrer in a container and the bidentate organophosphorus compound L-22 (42.9 mg, 0.040 mmol) was weighed out as a ligand of the hydroformylation reaction catalyst. Next, 1, 4-dioxane (0.5 ml) was added as a solvent to each of the above-mentioned glass containers A, B, C under a nitrogen atmosphere to dissolve each component, and then the solution of the glass container A was charged into a glass transferred to a container B, after stirring at room temperature for 5 minutes, the solution in the glass container B was further transferred to a glass container C with a cannula and stirred for 5 minutes. In addition, 1, 4-dioxane (0.5 ml) as a solvent was added to the autoclave under a nitrogen atmosphere and stirred for 5 minutes. Subsequently, the solution of the glass container C was transferred to an autoclave with a cannula, the inside of the glass container C was washed with 1, 4-dioxane (2.0 ml), and the washing liquid was also transferred to the autoclave. Further, 448.9 mg (cis-2-decene: 2.0 mmol, 1 mol / mol) of a mixed solution of cis-2-decene (reaction raw material) and n-dodecane (internal standard substance for GC analysis) N-dodecane: 1.0 mmol) was added. After sealing the autoclave, quickly hydrogen from a gas supply valve/ carbon monoxide mixed gas (mixing ratio: 1/1) was introduced up to 0.5 Mpa, Under stirring at 800 rpm with a magnetic stirrer, reacted for 18 hours while heating at 120°C in an electric furnace (the amount of 1,4-dioxane used is 88% by weight based on the total weight of the reaction medium). After completion of the reaction, the reaction was cooled down to room temperature and the residual gas was released, and then the reaction results were analyzed by NMR and gas chromatography. As a result, undecanal yield was 4.0%, undecanol yield was 62.2%. In addition, the ratio (L / B ratio) of linear alcohol (1-undecanol) to branched alcohol (2-methyl-1-decanol etc.) in undecanol was 17 (linear selectivity = 94% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | 32 g (0.80 mol) of 60percent sodium hydride (NaH) was added to 1 L of toluene, 63.8 g (0.37 mol) of undecanol was slowly added dropwise and the mixture was stirred at 50 for 1 hour. 100 g (0.31 mol) of <strong>[56523-59-2]15-bromopentadecanoic acid</strong> are mixed with 250 ml of toluene and slowly added dropwise, and the mixture is refluxed for 48 hours. When the reaction was completed, the reaction was quenched with water and the organic layer was extracted with ethyl acetate and recrystallized in n-hexane. The obtained solid was dried under reduced pressure to obtain 103.6 g of a white powder of 15- (undecyloxy) pentadecanoic acid in a yield of 81percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With toluene-4-sulfonic acid In toluene at 110℃; Inert atmosphere; Schlenk technique; | 5a: 3-(undecyloxy)thiophene synthesized by following Scheme 3 A mixture of 3-methoxythiophene 4 (10.00 g, 87.60 mmol), undecan-1-ol (30.2 g, 175.2 mmol), p-toluenesulfonic acid monohydrate (1.67 g, 0.1 eq) and 65 ml toluene was heated in a 110 °C bath overnight under argon. After dichloromethane/water extraction, the organic phase was dried over MgSO4. The solvent was then removed by rotvap, and the residue was purified by column chromatography (silica gel) using petroleum ether as eluent to give 5a as a colorless oil (13.8 g, 62 %).‘H NMR (400 MHz, CDC13, ppm): 7.17 (dd, 1H), 6.75 (dd, 1H), 6.29 (dd, 1H), 3.93 (t, 2H), 1.92-1.65 (m, 2H), 1.51-1.11 (m, 16H), 0.88 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In dichloromethane; N,N-dimethyl-formamide; at 20℃; | General procedure: Ester prodrugs of BEX and RA were synthesised by adding2.87 mmol of the desired alcohol to 0.287 mmol of BEX or RA. 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (0.431 mmol) and 4-dimethylaminopyridine(0.057 mmol) were added, and dichloromethane(15 mL) was used as the solvent. The mixture was stirred magneticallyovernight at room temperature. Purification was performed by flashchromatography using a 200-400 mesh silica gel-packed glass columnsand hexane-ethyl acetate 50:2 (v/v) as the mobile phase. Specific detailsfor compounds that were obtained by different synthetic schemesare described in Supplementary Material 1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: tert-butyl glycidyl ether With trifluorormethanesulfonic acid; triethylamine In dichloromethane at -20℃; for 6h; Stage #2: undecyl alcohol With tetrabutylammomium bromide; caesium carbonate In tetrahydrofuran at 120℃; for 3h; | 1 Embodiment 1 The reaction bottle into the 59 g 2 - tert-butoxy ethanol, 65 g triethylamine and 300 ml of dichloromethane, cooled to -20 °C, slowly dropping 156 g trifluoromethanesulfonic anhydride. The completion of the dropping, stirring for 6 hours; cold water quenching reaction, liquid, organic phase dried, concentrated.Concentrate shifts into 1 in boost strength cauldron, respectively adding 300 ml of tetrahydrofuran, is n-undecanol 95 g, 10 g tert-butylammonium bromide and 110 g cesium carbonate, after sealing with the temperature rising to 120 °C, thermal insulation reaction 3 hours; cooling to heating, suction filtering to remove the solid, concentrated to remove the solvent, adding water and dichloromethane stirring, liquid. The organic phase by adding 50 ml of trifluoroacetic acid, at room temperature the reaction is complete, adding 250 ml of water quenching reaction, liquid, aqueous phase dichloromethane is used for extraction, the combined organic phase, concentrated, distilled under reduced pressure to obtain 56 g Hendecane phenoxy ethanol, the product purity 99.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | In N,N-dimethyl-formamide at 37℃; for 48h; Inert atmosphere; | 3.1.1. General Procedure for the Synthesis of(±)-1-(4'-Acetoxycyclopent-1'-yl)-5-alkyloxy-methyluracils 1-3 General procedure: The corresponding alcohol (1.5 mmol) was added to a solution of 1-(4'-acetoxycyclopent-1'-yl)-5-(bromomethyl)uracil (13, 0.5 mmol) in dry DMF (10 mL). The mixture was stirred for 48 h at37 °C under argon atmosphere, evaporated under vacuum, and the residue dissolved in CHCl3 (5 mL),loaded onto a silica gel column, and eluted with CHCl3:MeOH (98:2) to provide the crude productswhich were purified as described below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.62% | With triethylamine In tetrahydrofuran at 0 - 20℃; for 16h; | 31.1 Step 1: Preparation of 4-nitrophenyl undecyl carbonate Undecan-l-ol (0.3 g, 1.741mmol) was dissolved in THF (20 mL) and cooled to 0°C. TEA was added (0.7mL, 5.223 mmol) followed by 4-nitrophenyl chloroformate (0.462, 2.089mmol). The reaction mixture was stirred at room temperature for 16 h, extracted with EtOAc (3 X 30 mL), washed with brine (30 mL) and concentrated. The crude product was purified using flash chromatography, eluting with 5-10% MeOEfDCM, to give 4-nitrophenyl undecyl carbonate. (0.55 g, 93.62%). NMR: (400 MHz, DMSO) d ppm: 0.84-0.88(t, J=1.2Hz, 1H). 1.26-1.35(m, 8H), 1.65-1.70(m, 1H), 3.34(s, 1H), 4.23-4.26(t, J=6.8Hz, 1H), 7.56-7.58(m, lH),8.31-8.33(m 1H). |
93.62% | With triethylamine In tetrahydrofuran at 0 - 20℃; for 16h; | 31.1 Step 1: Preparation of 4-nitrophenyl undecyl carbonate Undecan-l-ol (0.3 g, 1.741mmol) was dissolved in THF (20 mL) and cooled to 0°C. TEA was added (0.7mL, 5.223 mmol) followed by 4-nitrophenyl chloroformate (0.462, 2.089mmol). The reaction mixture was stirred at room temperature for 16 h, extracted with EtOAc (3 X 30 mL), washed with brine (30 mL) and concentrated. The crude product was purified using flash chromatography, eluting with 5-10% MeOEfDCM, to give 4-nitrophenyl undecyl carbonate. (0.55 g, 93.62%). NMR: (400 MHz, DMSO) d ppm: 0.84-0.88(t, J=1.2Hz, 1H). 1.26-1.35(m, 8H), 1.65-1.70(m, 1H), 3.34(s, 1H), 4.23-4.26(t, J=6.8Hz, 1H), 7.56-7.58(m, lH),8.31-8.33(m 1H). |
43.34% | With triethylamine In dichloromethane at 25℃; for 12h; Inert atmosphere; |
43.34% | With triethylamine In dichloromethane at 25℃; for 12h; Inert atmosphere; | 2.2A Example 2: Step 2A: Synthesis of (4-nitrophenyl) undecyl carbonate To a mixture of undecan-1-ol (40 g, 232.14 mmol, 1 eq) in DCM (600 mL) was added TEA (46.98 g, 464.29 mmol, 64.62 mL, 2 eq) (4-nitrophenyl) carbonochloridate (70.19 g, 348.22 mmol, 1.5 eq) was added to the former mixture portionwise under N2. The mixture was stirred at 25° C. for 12 hr. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was purified by column chromatography. Compound (4-nitrophenyl) undecyl carbonate (33.95 g, 100.62 mmol, 43.34% yield) was obtained as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65.07% | With pyridine In dichloromethane at 0 - 25℃; for 12h; Inert atmosphere; | |
65.07% | With pyridine In dichloromethane at 0 - 25℃; for 12h; Inert atmosphere; | 4.4A Example 4: Step 4A: Synthesis of Chloromethyl Undecyl Carbonate To a mixture of undecan-1-ol (80 g, 464.29 mmol, 1 eq) and pyridine (73.45 g, 928.58 mmol, 74.95 mL, 2 eq) in DCM (600 mL) was added chloromethyl carbonochloridate (119.73 g, 928.58 mmol, 82.57 mL, 2 eq) dropwise at 0° C. under N2. The mixture was stirred at 25° C. for 12 h. The reaction mixture was extracted by DCM 1500 mL (500 mL*3). The organic phase was separated, washed with brine 30 mL (150 mL*2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=50/1 to 1:1). Compound chloromethyl undecyl carbonate (80 g, 302.13 mmol, 65.07% yield) was obtained as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With platinum(IV) oxide; hydrogen In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Autoclave; | Condition B: The cross-metathesis reaction allyl alcohol with 1-octene General procedure: Theprimary allyl alcohols with various chain lengths could be obtained by the reaction of allyl alcohol with a terminal olefin using Hoveyda-Grubbs II. The typical procedure for synthesis of 1-nonanol is as follows: a solution of allyl alcohol (0.5 mmol) and 1-octene (1 mmol) in dichloromethane (2.5 mL) was charged into a 10 mL vial followed by Hoveyda- Grubbs II (0.01 mmol) in under an argon atmosphere, and then the via was placed in a 50 mL stainless autoclave. The autoclave was purged with H2 three times and pressurized by H2 (0.3 MPa), and vigorously stirred at room temperature for 50 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90 %Chromat. | With platinum(IV) oxide; Hoveyda-Grubbs catalyst second generation; hydrogen In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Autoclave; | Condition A: Tandem cross-metathesis/hydrogenation reaction allyl alcohol with 1-octene General procedure: The primary alcohols with various chain lengths could be obtained by the reaction of allyl alcohol with a terminal olefin using Hoveyda-Grubbs II and PtO2 catalyst together in one pot. The typical procedure for synthesis of 1-nonanol is as follows: a solution of allyl alcohol (0.5 mmol) and 1-octene (1 mmol) in dichloromethane (2.5 mL) was charged into a 10 mL vial followed by Hoveyda-Grubbs II (0.01 mmol) and PtO2 (0.01 mmol) in under an argon atmosphere, and then the via was placed in a 50 mL stainless autoclave. The autoclave was purged with H2 three times and pressurized by H2 (0.3 MPa), and vigorously stirred at room temperature for 50 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: undecyl alcohol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.5h; Stage #2: 5,5-bis-bromomethyl-2,2-dimethyl-[1,3]dioxane In N,N-dimethyl-formamide; mineral oil at 100℃; for 15h; Further stages; | 2.2-1; 5.5-1 General Procedure for Synthesis of 2,2′-(thiobis(methylene))bis(2-(alkyloxy)methyl)propane-1,3-diol (Steps f-h of FIG. 2) General procedure: NaH (11.6 mmol, 1.2 equivalents, 60%) was added to a solution of a 1-alkanol (11.6 mmol, 1 equivalent) in anhydrous DMF (25 mL) at 0° C. The mixture was stirred at room temperature for 30 minutes, and then 5,5-bis-bromomethyl-2,2-dimethyl-[1,3]dioxane (11.6 mmol, 1 equivalent) was added. A reaction vessel was transferred to an oil container preheated to 100° C., and further stirring was carried out for 15 hours. After the completion of the reaction (monitored by TLC), a reaction mixture was cooled at room temperature, rapidly cooled with ice-cold H2O (50 mL), and extracted with ether (3×100 mL). A mixed organic layer was washed with brine (2×150 mL), dried with anhydrous Na2SO4, and concentrated using a rotary evaporator. A product (5.08 mmol, 1 equivalent) was dissolved in DMF (20 mL), and KI (5.08 mmol, 1 equivalent) was added to the solution. Following the addition of Na2S. 9H2O (0.6 equivalents) in water (5 mL) to the mixture, DMF (20 mL) was further added, and the mixture was stirred for 20 hours at 90° C. under nitrogen (N2). After cooling, the mixture was poured into water (300 mL) and extracted with ether (150 mL). The extract was sequentially washed with water (300 mL), a 2.5% NaOH solution (300 mL) and brine (100 mL), and dried with anhydrous Na2SO4. The reaction mixture was stirred with 3 g of silica gel, filtered, and concentrated by rotary evaporation. The concentrated reaction mixture was dissolved in a 1:1 mixture of CH2Cl2 and MeOH (50 mL), p-toluenesulfonic acid (p-TSA) monohydrate (200 mg) was added, and then the resulting mixture was stirred for 6 hours at room temperature. Following the completion of the mixture, the reaction mixture was neutralized with a NaHCO3 solution, filtered, and dried by rotary evaporation. By flash column chromatography (EtOAc/hexane), a white solid, thioether-containing tetraol (Compound H) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; 1,10-Phenanthroline; triethylamine In 1,2-dichloro-ethane at 120℃; for 16h; Autoclave; Sealed tube; | 4.2 General procedures for one-pot tandem hydroformylation-transfer hydrogenation of olefins with CO and FA General procedure: In a typical experiment, [Ir(COD)Cl]2 (0.025mmol), L1 (0.05mmol) (or the other ligand) were mixed with styrene (5mmol, or the other olefin), FA (25mmol), Et3N (0.125mol if required) and DCE (2mL, or the other solvent). The mixture was added in a 50mL sealed Teflon-lined stainless steel autoclave which was purged with CO (0.5MPa) for three times and then pressured by CO to 3.0MPa. Then the reaction mixture was stirred vigorously at appointed temperature for some time. Upon completion, the autoclave was cooled down to room temperature and slowly depressurized. The solution was analyzed by GC to determine the conversions (n-dodecane as internal standard) and the selectivities (normalization method), and the products were further identified by GC-mass spectrometry. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 73% 2: 14% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20 - 22℃; for 3h; | 4.1.1 General procedures for the preparation of 5Z,9Z-dienoic acids 5a-g, 6a-g General procedure: To a solution of a mixture of alcohol (R-OH, R=C8H17, C9H19, C11H23, C16H33, o-naphthyl, p-naphthyl, benzyl) (40mmol), tetradeca-5,9-diendicarboxylic acid (30mmol) and 4-dimethylaminopyridine (4mmol) in CH2Cl2 (150ml) at room temperature (20-22°C) a solution of dicyclohexylcarbodiimide (40mmol) in CH2Cl2 (120ml) was dripped. The reaction mixture was stirred at room temperature (20-22°C) for 3h. The precipitate was removed by filtration, the solution was concentrated under vacuum. The reaction product was separated by column chromatography (Acrus silica gel (0.060-0.200mm), eluent petroleum ether / ethyl acetate) [38]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | Stage #1: β-maltose octaacetate With tin(IV) chloride In dichloromethane at 0℃; for 0.25h; Inert atmosphere; Stage #2: undecyl alcohol In dichloromethane at 0℃; for 80h; Inert atmosphere; diastereoselective reaction; | General procedure for the synthesis of alkylhepta-O-acetyl-β-maltosides General procedure: Tin(IV) chloride (2.0 equiv) was added very slowly to a solution of maltose octaacetate (1.0 mmol) in anhydrous methylene chloride (1.0 mL) at 0°C under a nitrogen atmosphere. After 15 min, the corresponding alcohol or thiol (3.0 equiv) was added slowly at 0°C (at -10°C in the case of thiol), and the mixture was stirred 0°C (or -10°C) for 80 min. The progress of the reaction was monitored by TLC on silica gel plates using ethylacetate-hexane (1:1) as eluent. The mixture was diluted with cold (0°C) ethyl acetate, quenched with water, and extracted with ethyl acetate (3×50 mL). The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure, and the residue was purified by column chromatography on Dowex (OH form) using ethyl acetate-hexane (15:100,20:100, and 25:100) as eluent. The products were isolated as colorless viscous oils. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium hydroxide / tetrahydrofuran / 4 h / 0 - 40 °C 2: tetra-(n-butyl)ammonium iodide / 0.5 h / 130 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1-n-butyl-3-methylimidazolium hydrogen sulfate at 60℃; for 20h; Large scale; | 1.2 Step 2 can add compound e1 6-bromohexanoic acid (10mol, 1.95kg) and compound d1 undecyl alcohol (15mol, 2.58kg) without organic solvent, and add equimolar amount of ionic liquid (Such as 1-butyl-3-methylimidazole hydrogen sulfate) heating, heating temperature is 60, react for 20 hours, TLC detects the reaction, after the reaction is complete, cool to room temperature, stand still, the upper organic phase is separated, the lower layer is ions Liquid layer. The upper organic phase is distilled under reduced pressure to obtain compound f1 (undecyl 6-bromohexanoate) and recover excess undecyl alcohol. The yield of compound f1 is 90% and the purity is 99%. |
38.6% | With 4-dimethylaminopyridine; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 18h; | 2.1 Step 1: Synthesis of Compound 2-1 6-Bromohexanoic acid (1.0 g, 5.13 mmol)and undecanol (1.77 g, 10.25 mmol) in dichloromethane (60 mL),Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC hydrochloride, 0.98 g, 5.13 mmol)and DMAP (0.125 g, 1.03 mmol).The mixture was stirred at normal temperature for 18 hours.After the reaction was completed, it was diluted with DCM (200 mL),and washed with saturated NaHCO3 (100 mL) and brine (100 mL).The combined organic layers were dried over anhydrous Na2SO4, the solvent was removed in vacuo,A crude product was obtained, which was purified by chromatography (silica gel column, eluent: petroleum ether containing 0.5% EA (volume percent)), and the pure product was evaporated,Obtain light yellow oily compound 2-1 (undecyl 6-bromohexanoate)(0.69 g, 38.6% yield). |
38.6% | With 4-dimethylaminopyridine; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 18h; | 2.1 Step 1: Synthesis of compounds 2-1 6-Bromohexanoic acid (1.0 g, 5.13 mmol) and undecyl alcohol (1.77 g, 10.25 mmol) were dissolved in dichloromethane (60 mL) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride ( EDC hydrochloride, 0.98 g, 5.13 mmol) and DMAP (0.125 g, 1.03 mmol) were added. The mixture was stirred at room temperature for 18 hours. After the reaction is over, dilute with DCM (200 mL) and wash with saturatedNaHCO3(100 mL) and brine (100 mL). The combined organic layer was dried with anhydrousNa2SO4, the solvent was removed in vacuo, the crude product was obtained by chromatography (silica gel column, eluent is petroleum ether containing 0.5% EA (volume percentage)), and the pure product was evaporated to give a light yellow oily compound 2-1 (6-bromohexanoate) (0.69g, yield 38.6%). |
With 4-dimethylaminopyridine; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With trifluorormethanesulfonic acid In neat (no solvent) at 0 - 20℃; for 4h; Inert atmosphere; | O-Acetylation Reaction; General Procedure General procedure: To a round-bottomed flask charged with a magnetic stirrer and 1a-l(1.0 equiv) was added trimethylsilyl acetate (2.0 equiv for 1a-g and1j-k; 5.0 equiv for 1l) and TfOH (0.05 equiv for 1a-g and 1j-k; 0.1equiv for 1l) under a N2 atmosphere in an ice bath. The reaction mixturewas removed from the ice bath and then stirred at rt for an appropriateperiod (4 h for 1a-g and 1j-k; 12 h for 1l). After completionof the reaction, the mixture was concentrated. The crude productswere purified by column chromatography on silica gel to give the desiredproducts 2a-l. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine In neat (no solvent) at 20℃; for 2h; | O-Trimethylsilylation Reaction; General Procedure General procedure: To a round-bottomed flask charged with a magnetic stirrer and 1a-lwas added trimethylsilyl acetate (2.0 equiv) and Et3N (1.0 equiv). Thereaction mixture was then sitrred at rt for 2 h. After completion of thereaction, the mixture was concentrated. The crude products were purifiedby column chromatography on silica gel to give the desiredproducts 4a-l. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With trifluorormethanesulfonic acid In neat (no solvent) at 80℃; for 8h; | O-Benzoylation Reaction; General Procedure General procedure: To a round-bottomed flask charged with a magnetic stirrer and 1a-lwas added trimethylsilyl benzoate (2.0 equiv) and TfOH (0.1 equiv).The reaction mixture was then sitrred in an oil bath at 80 °C for 8 h.After completion of the reaction, the mixture was concentrated. Thecrude products were purified by column chromatography on silica gelto give the desired products 3a-l. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 25℃; | 54.1 Step 1: UnDecyl (S)-2-((tert-butoxycarbonyl)amino)-3-(3, 5-difluorophenyl)propanoate To a stirred solution of (S)-2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoic acid (5 g, 16.60 mmol) in DCM (80 mL) was added DMAP (0.203 g, 1.660 mmol) and EDC (4.14 g, 21.57 mmol) at 0 °C. Afte for 30 min, undecan-1-ol(3.72 g, 21.57 mmol) was added at 0 °C and the resulting reaction mixture was stirred at 25 °C for 4 h. LCMS showed the reaction was completed. The reaction mixture was diluted with water (50 mL) and extracted with DCM (2 c 100 mL). The combined organic layers were washed with brine (40 mL), dried over NasSC, filtered and concentrated to afford unDecyl (S)-2-((tert- butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoate (6.9 g, 15.15 mmol, 91 % yleld) as a yellow solid which was used in the next step without further purification. LCMS: (M+Na) = 478.1; Retention time (0.1% TFA) = 2 80 min. |
91% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 25℃; | 54.1 Step 1: UnDecyl (S)-2-((tert-butoxycarbonyl)amino)-3-(3, 5-difluorophenyl)propanoate To a stirred solution of (S)-2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoic acid (5 g, 16.60 mmol) in DCM (80 mL) was added DMAP (0.203 g, 1.660 mmol) and EDC (4.14 g, 21.57 mmol) at 0 °C. Afte for 30 min, undecan-1-ol(3.72 g, 21.57 mmol) was added at 0 °C and the resulting reaction mixture was stirred at 25 °C for 4 h. LCMS showed the reaction was completed. The reaction mixture was diluted with water (50 mL) and extracted with DCM (2 c 100 mL). The combined organic layers were washed with brine (40 mL), dried over NasSC, filtered and concentrated to afford unDecyl (S)-2-((tert- butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoate (6.9 g, 15.15 mmol, 91 % yleld) as a yellow solid which was used in the next step without further purification. LCMS: (M+Na) = 478.1; Retention time (0.1% TFA) = 2 80 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.64% | With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 30 - 35℃; for 8h; | 1.1 Step 1: Synthesis of preparation of n-undecyl 4-bromobutyrate (YK-001-PM1) n-Undecanol (5.00 g, 29.02 mmol) and 4-bromobutyric acid (5.14 g, 30.78 mmol) were dissolved in dichloromethane (40 mL),To the above solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.67 g, 34.82 mmol) and 4-dimethylaminopyridine (177 mg, 1.45 mmol), and The reaction was stirred at 30~35°C for 8 hours. After the completion of the reaction, the reaction solution was washed with saturated sodium carbonate, saturated brine, and dried over Na2SO4. The mixture was filtered and the filtrate was concentrated in vacuo under reduced pressure. The residue was purified by silica gel chromatography to give n-undecyl 4-bromobutyrate (6.68 g, 20.79 mmol, 71.64%). |
71.64% | With dmap; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 30 - 35℃; for 8h; | 1.1 Step 1: Synthesis of preparation of n-undecyl 4-bromobutyrate (YK-001-PM1) n-Undecanol (5.00 g, 29.02 mmol) and 4-bromobutyric acid (5.14 g, 30.78 mmol) were dissolved in dichloromethane (40 mL),To the above solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.67 g, 34.82 mmol) and 4-dimethylaminopyridine (177 mg, 1.45 mmol), and The reaction was stirred at 30~35°C for 8 hours. After the completion of the reaction, the reaction solution was washed with saturated sodium carbonate, saturated brine, and dried over Na2SO4. The mixture was filtered and the filtrate was concentrated in vacuo under reduced pressure. The residue was purified by silica gel chromatography to give n-undecyl 4-bromobutyrate (6.68 g, 20.79 mmol, 71.64%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: 5-bromopentyl alcohol; 4-Nitrophenyl chloroformate With 4-dimethylaminopyridine In dichloromethane at 20℃; for 3h; Stage #2: undecyl alcohol In dichloromethane at 20℃; | 2 Synthesis of 5-bromopentylundecyl carbonate (2c) 5-Bromopentanol (0.84 g, 5.0 mmol) was dissolved in 30 mL of dichloromethane, 4-dimethylaminopyridine (1.22 g, 10 mmol) was added, and phenyl p-nitrochloroformate (1.11 g) was added in batches , 5.5 mmol), the reaction was stirred at room temperature for 3 h, undecanol (0.97 g, 5.6 mmol) was added to the reaction solution, and the mixture was stirred at room temperature overnight. After TLC showed that the reaction was complete, 20 mL of dichloromethane was added to dilute, and then 30 mL of Washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and separated by column chromatography to obtain 5-bromopentylundecyl carbonate 2c (1.20 g, pale yellow oil) in a yield of 66%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: 1-bromo-6-hexanol; 4-Nitrophenyl chloroformate With 4-dimethylaminopyridine In dichloromethane at 20℃; for 3h; Stage #2: undecyl alcohol In dichloromethane at 20℃; | 3 Synthesis of 6-Bromohexylundecylcarbonate (3a) 6-Bromo-n-hexanol (0.91 g, 5.0 mmol) was dissolved in 30 mL of dichloromethane, 4-dimethylaminopyridine (0.90 g, 7.5 mmol) was added, and p-nitrophenyl chloroformate (1.20 mmol) was added in batches g, 6.0 mmol), the reaction was stirred at room temperature for 3 h, undecanol (0.97 g, 5.6 mmol) was added to the reaction solution, and the mixture was stirred at room temperature overnight. After TLC showed that the reaction was complete, 20 mL of dichloromethane was added to dilute, and then Washed with 30 mL of saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and separated by column chromatography to obtain 6-bromohexylundecyl carbonate 3a (1.25 g, pale yellow oil) in a yield of 66%. |
Tags: 112-42-5 synthesis path| 112-42-5 SDS| 112-42-5 COA| 112-42-5 purity| 112-42-5 application| 112-42-5 NMR| 112-42-5 COA| 112-42-5 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :